cpgIslandExt CpG Islands CpG Islands (Islands < 300 Bases are Light Green) Expression and Regulation Description CpG islands are associated with genes, particularly housekeeping genes, in vertebrates. CpG islands are typically common near transcription start sites and may be associated with promoter regions. Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the Cs in such an arrangement tend to be methylated. This methylation helps distinguish the newly synthesized DNA strand from the parent strand, which aids in the final stages of DNA proofreading after duplication. However, over evolutionary time, methylated Cs tend to turn into Ts because of spontaneous deamination. The result is that CpGs are relatively rare unless there is selective pressure to keep them or a region is not methylated for some other reason, perhaps having to do with the regulation of gene expression. CpG islands are regions where CpGs are present at significantly higher levels than is typical for the genome as a whole. The unmasked version of the track displays potential CpG islands that exist in repeat regions and would otherwise not be visible in the repeat masked version. By default, only the masked version of the track is displayed. To view the unmasked version, change the visibility settings in the track controls at the top of this page. Methods CpG islands were predicted by searching the sequence one base at a time, scoring each dinucleotide (+17 for CG and -1 for others) and identifying maximally scoring segments. Each segment was then evaluated for the following criteria: GC content of 50% or greater length greater than 200 bp ratio greater than 0.6 of observed number of CG dinucleotides to the expected number on the basis of the number of Gs and Cs in the segment The entire genome sequence, masking areas included, was used for the construction of the track Unmasked CpG. The track CpG Islands is constructed on the sequence after all masked sequence is removed. The CpG count is the number of CG dinucleotides in the island. The Percentage CpG is the ratio of CpG nucleotide bases (twice the CpG count) to the length. The ratio of observed to expected CpG is calculated according to the formula (cited in Gardiner-Garden et al. (1987)): Obs/Exp CpG = Number of CpG * N / (Number of C * Number of G) where N = length of sequence. The calculation of the track data is performed by the following command sequence: twoBitToFa assembly.2bit stdout | maskOutFa stdin hard stdout \ | cpg_lh /dev/stdin 2> cpg_lh.err \ | awk '{$2 = $2 - 1; width = $3 - $2; printf("%s\t%d\t%s\t%s %s\t%s\t%s\t%0.0f\t%0.1f\t%s\t%s\n", $1, $2, $3, $5, $6, width, $6, width*$7*0.01, 100.0*2*$6/width, $7, $9);}' \ | sort -k1,1 -k2,2n > cpgIsland.bed The unmasked track data is constructed from twoBitToFa -noMask output for the twoBitToFa command. Data access CpG islands and its associated tables can be explored interactively using the REST API, the Table Browser or the Data Integrator. All the tables can also be queried directly from our public MySQL servers, with more information available on our help page as well as on our blog. The source for the cpg_lh program can be obtained from src/utils/cpgIslandExt/. The cpg_lh program binary can be obtained from: http://hgdownload.soe.ucsc.edu/admin/exe/linux.x86_64/cpg_lh (choose "save file") Credits This track was generated using a modification of a program developed by G. Miklem and L. Hillier (unpublished). References Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261-82. PMID: 3656447 cpgIslandSuper CpG Islands CpG Islands (Islands < 300 Bases are Light Green) Expression and Regulation Description CpG islands are associated with genes, particularly housekeeping genes, in vertebrates. CpG islands are typically common near transcription start sites and may be associated with promoter regions. Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the Cs in such an arrangement tend to be methylated. This methylation helps distinguish the newly synthesized DNA strand from the parent strand, which aids in the final stages of DNA proofreading after duplication. However, over evolutionary time, methylated Cs tend to turn into Ts because of spontaneous deamination. The result is that CpGs are relatively rare unless there is selective pressure to keep them or a region is not methylated for some other reason, perhaps having to do with the regulation of gene expression. CpG islands are regions where CpGs are present at significantly higher levels than is typical for the genome as a whole. The unmasked version of the track displays potential CpG islands that exist in repeat regions and would otherwise not be visible in the repeat masked version. By default, only the masked version of the track is displayed. To view the unmasked version, change the visibility settings in the track controls at the top of this page. Methods CpG islands were predicted by searching the sequence one base at a time, scoring each dinucleotide (+17 for CG and -1 for others) and identifying maximally scoring segments. Each segment was then evaluated for the following criteria: GC content of 50% or greater length greater than 200 bp ratio greater than 0.6 of observed number of CG dinucleotides to the expected number on the basis of the number of Gs and Cs in the segment The entire genome sequence, masking areas included, was used for the construction of the track Unmasked CpG. The track CpG Islands is constructed on the sequence after all masked sequence is removed. The CpG count is the number of CG dinucleotides in the island. The Percentage CpG is the ratio of CpG nucleotide bases (twice the CpG count) to the length. The ratio of observed to expected CpG is calculated according to the formula (cited in Gardiner-Garden et al. (1987)): Obs/Exp CpG = Number of CpG * N / (Number of C * Number of G) where N = length of sequence. The calculation of the track data is performed by the following command sequence: twoBitToFa assembly.2bit stdout | maskOutFa stdin hard stdout \ | cpg_lh /dev/stdin 2> cpg_lh.err \ | awk '{$2 = $2 - 1; width = $3 - $2; printf("%s\t%d\t%s\t%s %s\t%s\t%s\t%0.0f\t%0.1f\t%s\t%s\n", $1, $2, $3, $5, $6, width, $6, width*$7*0.01, 100.0*2*$6/width, $7, $9);}' \ | sort -k1,1 -k2,2n > cpgIsland.bed The unmasked track data is constructed from twoBitToFa -noMask output for the twoBitToFa command. Data access CpG islands and its associated tables can be explored interactively using the REST API, the Table Browser or the Data Integrator. All the tables can also be queried directly from our public MySQL servers, with more information available on our help page as well as on our blog. The source for the cpg_lh program can be obtained from src/utils/cpgIslandExt/. The cpg_lh program binary can be obtained from: http://hgdownload.soe.ucsc.edu/admin/exe/linux.x86_64/cpg_lh (choose "save file") Credits This track was generated using a modification of a program developed by G. Miklem and L. Hillier (unpublished). References Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261-82. PMID: 3656447 rmsk RepeatMasker Repeating Elements by RepeatMasker Variation and Repeats Description This track was created by using Arian Smit's RepeatMasker program, which screens DNA sequences for interspersed repeats and low complexity DNA sequences. The program outputs a detailed annotation of the repeats that are present in the query sequence (represented by this track), as well as a modified version of the query sequence in which all the annotated repeats have been masked (generally available on the Downloads page). RepeatMasker uses the Repbase Update library of repeats from the Genetic Information Research Institute (GIRI). Repbase Update is described in Jurka (2000) in the References section below. Some newer assemblies have been made with Dfam, not Repbase. You can find the details for how we make our database data here in our "makeDb/doc/" directory. Display Conventions and Configuration In full display mode, this track displays up to ten different classes of repeats: Short interspersed nuclear elements (SINE), which include ALUs Long interspersed nuclear elements (LINE) Long terminal repeat elements (LTR), which include retroposons DNA repeat elements (DNA) Simple repeats (micro-satellites) Low complexity repeats Satellite repeats RNA repeats (including RNA, tRNA, rRNA, snRNA, scRNA, srpRNA) Other repeats, which includes class RC (Rolling Circle) Unknown The level of color shading in the graphical display reflects the amount of base mismatch, base deletion, and base insertion associated with a repeat element. The higher the combined number of these, the lighter the shading. A "?" at the end of the "Family" or "Class" (for example, DNA?) signifies that the curator was unsure of the classification. At some point in the future, either the "?" will be removed or the classification will be changed. Methods Data are generated using the RepeatMasker -s flag. Additional flags may be used for certain organisms. Repeats are soft-masked. Alignments may extend through repeats, but are not permitted to initiate in them. See the FAQ for more information. Credits Thanks to Arian Smit, Robert Hubley and GIRI for providing the tools and repeat libraries used to generate this track. References Smit AFA, Hubley R, Green P. RepeatMasker Open-3.0. http://www.repeatmasker.org. 1996-2010. Repbase Update is described in: Jurka J. Repbase Update: a database and an electronic journal of repetitive elements. Trends Genet. 2000 Sep;16(9):418-420. PMID: 10973072 For a discussion of repeats in mammalian genomes, see: Smit AF. Interspersed repeats and other mementos of transposable elements in mammalian genomes. Curr Opin Genet Dev. 1999 Dec;9(6):657-63. PMID: 10607616 Smit AF. The origin of interspersed repeats in the human genome. Curr Opin Genet Dev. 1996 Dec;6(6):743-8. PMID: 8994846 refGene RefSeq Genes RefSeq Genes Genes and Gene Predictions Description The RefSeq Genes track shows known zebrafish protein-coding and non-protein-coding genes taken from the NCBI RNA reference sequences collection (RefSeq). The data underlying this track are updated weekly. Please visit the Feedback for Gene and Reference Sequences (RefSeq) page to make suggestions, submit additions and corrections, or ask for help concerning RefSeq records. For more information on the different gene tracks, see our Genes FAQ. Display Conventions and Configuration This track follows the display conventions for gene prediction tracks. The color shading indicates the level of review the RefSeq record has undergone: predicted (light), provisional (medium), reviewed (dark). The item labels and display colors of features within this track can be configured through the controls at the top of the track description page. Label: By default, items are labeled by gene name. Click the appropriate Label option to display the accession name instead of the gene name, show both the gene and accession names, or turn off the label completely. Codon coloring: This track contains an optional codon coloring feature that allows users to quickly validate and compare gene predictions. To display codon colors, select the genomic codons option from the Color track by codons pull-down menu. For more information about this feature, go to the Coloring Gene Predictions and Annotations by Codon page. Hide non-coding genes: By default, both the protein-coding and non-protein-coding genes are displayed. If you wish to see only the coding genes, click this box. Methods RefSeq RNAs were aligned against the zebrafish genome using BLAT. Those with an alignment of less than 15% were discarded. When a single RNA aligned in multiple places, the alignment having the highest base identity was identified. Only alignments having a base identity level within 0.1% of the best and at least 96% base identity with the genomic sequence were kept. Credits This track was produced at UCSC from RNA sequence data generated by scientists worldwide and curated by the NCBI RefSeq project. References Kent WJ. BLAT - the BLAST-like alignment tool. Genome Res. 2002 Apr;12(4):656-64. PMID: 11932250; PMC: PMC187518 Pruitt KD, Brown GR, Hiatt SM, Thibaud-Nissen F, Astashyn A, Ermolaeva O, Farrell CM, Hart J, Landrum MJ, McGarvey KM et al. RefSeq: an update on mammalian reference sequences. Nucleic Acids Res. 2014 Jan;42(Database issue):D756-63. PMID: 24259432; PMC: PMC3965018 Pruitt KD, Tatusova T, Maglott DR. NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D501-4. PMID: 15608248; PMC: PMC539979 cpgIslandExtUnmasked Unmasked CpG CpG Islands on All Sequence (Islands < 300 Bases are Light Green) Expression and Regulation Description CpG islands are associated with genes, particularly housekeeping genes, in vertebrates. CpG islands are typically common near transcription start sites and may be associated with promoter regions. Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the Cs in such an arrangement tend to be methylated. This methylation helps distinguish the newly synthesized DNA strand from the parent strand, which aids in the final stages of DNA proofreading after duplication. However, over evolutionary time, methylated Cs tend to turn into Ts because of spontaneous deamination. The result is that CpGs are relatively rare unless there is selective pressure to keep them or a region is not methylated for some other reason, perhaps having to do with the regulation of gene expression. CpG islands are regions where CpGs are present at significantly higher levels than is typical for the genome as a whole. The unmasked version of the track displays potential CpG islands that exist in repeat regions and would otherwise not be visible in the repeat masked version. By default, only the masked version of the track is displayed. To view the unmasked version, change the visibility settings in the track controls at the top of this page. Methods CpG islands were predicted by searching the sequence one base at a time, scoring each dinucleotide (+17 for CG and -1 for others) and identifying maximally scoring segments. Each segment was then evaluated for the following criteria: GC content of 50% or greater length greater than 200 bp ratio greater than 0.6 of observed number of CG dinucleotides to the expected number on the basis of the number of Gs and Cs in the segment The entire genome sequence, masking areas included, was used for the construction of the track Unmasked CpG. The track CpG Islands is constructed on the sequence after all masked sequence is removed. The CpG count is the number of CG dinucleotides in the island. The Percentage CpG is the ratio of CpG nucleotide bases (twice the CpG count) to the length. The ratio of observed to expected CpG is calculated according to the formula (cited in Gardiner-Garden et al. (1987)): Obs/Exp CpG = Number of CpG * N / (Number of C * Number of G) where N = length of sequence. The calculation of the track data is performed by the following command sequence: twoBitToFa assembly.2bit stdout | maskOutFa stdin hard stdout \ | cpg_lh /dev/stdin 2> cpg_lh.err \ | awk '{$2 = $2 - 1; width = $3 - $2; printf("%s\t%d\t%s\t%s %s\t%s\t%s\t%0.0f\t%0.1f\t%s\t%s\n", $1, $2, $3, $5, $6, width, $6, width*$7*0.01, 100.0*2*$6/width, $7, $9);}' \ | sort -k1,1 -k2,2n > cpgIsland.bed The unmasked track data is constructed from twoBitToFa -noMask output for the twoBitToFa command. Data access CpG islands and its associated tables can be explored interactively using the REST API, the Table Browser or the Data Integrator. All the tables can also be queried directly from our public MySQL servers, with more information available on our help page as well as on our blog. The source for the cpg_lh program can be obtained from src/utils/cpgIslandExt/. The cpg_lh program binary can be obtained from: http://hgdownload.soe.ucsc.edu/admin/exe/linux.x86_64/cpg_lh (choose "save file") Credits This track was generated using a modification of a program developed by G. Miklem and L. Hillier (unpublished). References Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261-82. PMID: 3656447 ctgPos2 Contigs Assembly Contigs Mapping and Sequencing Description This track is an alternate set of genbank identifier names for the chromosomes and assembled contigs. These names were taken directly from the following files at NCBI: Zv9/Primary_Assembly/localID2acc and Zv9/Primary_Assembly/assembled_chromosomes/chr2acc. gold Assembly Assembly from Fragments Mapping and Sequencing Description This track shows the Zebrafish Zv9 (Jul. 2010) assembly provided by The Wellcome Trust Sanger Institute. See also: Danio rerio Sequencing Project - FAQ, and: GRC Danio rerio genome overview. It contains scaffolds (supercontigs) totaling 1,412,464,843 bp. The assembly has been tied to the fingerprint contig (FPC) map (data freeze April 1, 2010), which provides a tiling path of sequenced clones. 1.41 Gb of sequence from 9,816 sequenced clones (8,276 finished and 1,090 unfinished) were used as a scaffold for the assembly. Gaps were filled with contigs from a whole genome shotgun (WGS) assembly of 6.5-7x coverage comprised of reads from a library created from a single Tuebingen doubled haploid zebrafish. Approximately 1.36 Gbp (96%) of the resulting integrated assembly were placed on chromosomes 1-25, including estimated gap sizes and 100 bp gaps inserted betweeen scaffolds. The complete sequence of the mitochondrion genome, which is shown as chrM in the Genome Browser, was obtained from GenBank, accession NC_002333.2. The entire assembly consists of chrM, 25 chromosomes, and 1,107 unplaced scaffolds that fall into two groups: Zv9_scaffold3453 - Zv9_scaffold3564 - sequences based on FPC contigs or linked to chromosomes via a marker (in 112 unmapped scaffolds) where scaffold3453 is the scaffold identifier. Zv9_NA1 - Zv9_NA999 - WGS contigs that could not be related to any FPC contig and could not be be placed on a chromosome (in 995 unmapped scaffolds) where NA1 is the scaffold identifier. The unplaced scaffolds contain 100 bp gaps that are shown in the Gap annotation. Components within this track are marked type "F" for finished sequences, type "W" for WGS contigs, and type "A" for active finishing. In dense mode, this track depicts the path through the draft and finished clones (aka the golden path) used to create the assembled sequence. Clone boundaries are distinguished by the use of alternating gold and brown coloration. Where gaps exist in the path, spaces are shown between the gold and brown blocks. If the relative order and orientation of the scaffolds between the two blocks is known, a line is drawn to bridge the blocks. For detailed information on the methods used to produce this assembly, see the Wellcome Trust Sanger Institute Danio rerio Sequencing Project website. Credits The Zv9 Zebrafish assembly was produced by The Wellcome Trust Sanger Institute, in collaboration with the Max Planck Institute for Developmental Biology, the Netherlands Institute for Developmental Biology (Hubrecht Laboratory), and Yi Zhou, Anthony DiBiase and Leonard Zon from the Boston Children's Hospital. augustusGene AUGUSTUS AUGUSTUS ab initio gene predictions v3.1 Genes and Gene Predictions Description This track shows ab initio predictions from the program AUGUSTUS (version 3.1). The predictions are based on the genome sequence alone. For more information on the different gene tracks, see our Genes FAQ. Methods Statistical signal models were built for splice sites, branch-point patterns, translation start sites, and the poly-A signal. Furthermore, models were built for the sequence content of protein-coding and non-coding regions as well as for the length distributions of different exon and intron types. Detailed descriptions of most of these different models can be found in Mario Stanke's dissertation. This track shows the most likely gene structure according to a Semi-Markov Conditional Random Field model. Alternative splicing transcripts were obtained with a sampling algorithm (--alternatives-from-sampling=true --sample=100 --minexonintronprob=0.2 --minmeanexonintronprob=0.5 --maxtracks=3 --temperature=2). The different models used by Augustus were trained on a number of different species-specific gene sets, which included 1000-2000 training gene structures. The --species option allows one to choose the species used for training the models. Different training species were used for the --species option when generating these predictions for different groups of assemblies. Assembly Group Training Species Fish zebrafish Birds chicken Human and all other vertebrates human Nematodes caenorhabditis Drosophila fly A. mellifera honeybee1 A. gambiae culex S. cerevisiae saccharomyces This table describes which training species was used for a particular group of assemblies. When available, the closest related training species was used. Credits Thanks to the Stanke lab for providing the AUGUSTUS program. The training for the chicken version was done by Stefanie König and the training for the human and zebrafish versions was done by Mario Stanke. References Stanke M, Diekhans M, Baertsch R, Haussler D. Using native and syntenically mapped cDNA alignments to improve de novo gene finding. Bioinformatics. 2008 Mar 1;24(5):637-44. PMID: 18218656 Stanke M, Waack S. Gene prediction with a hidden Markov model and a new intron submodel. Bioinformatics. 2003 Oct;19 Suppl 2:ii215-25. PMID: 14534192 cytoBandIdeo Chromosome Band (Ideogram) Ideogram for Orientation Mapping and Sequencing crisprRanges CRISPR Regions Genome regions processed to find CRISPR/Cas9 target sites (exons +/- 200 bp) Genes and Gene Predictions Description This track shows regions of the genome within 200 bp of transcribed regions and DNA sequences targetable by CRISPR RNA guides using the Cas9 enzyme from S. pyogenes (PAM: NGG). CRISPR target sites were annotated with predicted specificity (off-target effects) and predicted efficiency (on-target cleavage) by various algorithms through the tool CRISPOR. Display Conventions and Configuration The track "CRISPR Regions" shows the regions of the genome where target sites were analyzed, i.e. within 200 bp of transcribed regions as annotated by Ensembl transcript models. The track "CRISPR Targets" shows the target sites in these regions. The target sequence of the guide is shown with a thick (exon) bar. The PAM motif match (NGG) is shown with a thinner bar. Guides are colored to reflect both predicted specificity and efficiency. Specificity reflects the "uniqueness" of a 20mer sequence in the genome; the less unique a sequence is, the more likely it is to cleave other locations of the genome (off-target effects). Efficiency is the frequency of cleavage at the target site (on-target efficiency). Shades of gray stand for sites that are hard to target specifically, as the 20mer is not very unique in the genome: impossible to target: target site has at least one identical copy in the genome and was not scored hard to target: many similar sequences in the genome that alignment stopped, repeat? hard to target: target site was aligned but results in a low specificity score <= 50 (see below) Colors highlight targets that are specific in the genome (MIT specificity > 50) but have different predicted efficiencies: unable to calculate Doench/Fusi 2016 efficiency score low predicted cleavage: Doench/Fusi 2016 Efficiency percentile <= 30 medium predicted cleavage: Doench/Fusi 2016 Efficiency percentile > 30 and < 55 high predicted cleavage: Doench/Fusi 2016 Efficiency > 55 Mouse-over a target site to show predicted specificity and efficiency scores: The MIT Specificity score summarizes all off-targets into a single number from 0-100. The higher the number, the fewer off-target effects are expected. We recommend guides with an MIT specificity > 50. The efficiency score tries to predict if a guide leads to rather strong or weak cleavage. According to (Haeussler et al. 2016), the Doench 2016 Efficiency score should be used to select the guide with the highest cleavage efficiency when expressing guides from RNA PolIII Promoters such as U6. Scores are given as percentiles, e.g. "70%" means that 70% of mammalian guides have a score equal or lower than this guide. The raw score number is also shown in parentheses after the percentile. The Moreno-Mateos 2015 Efficiency score should be used instead of the Doench 2016 score when transcribing the guide in vitro with a T7 promoter, e.g. for injections in mouse, zebrafish or Xenopus embryos. The Moreno-Mateos score is given in percentiles and the raw value in parentheses, see the note above. Click onto features to show all scores and predicted off-targets with up to four mismatches. The Out-of-Frame score by Bae et al. 2014 is correlated with the probability that mutations induced by the guide RNA will disrupt the open reading frame. The authors recommend out-of-frame scores > 66 to create knock-outs with a single guide efficiently. Off-target sites are sorted by the CFD (Cutting Frequency Determination) score (Doench et al. 2016). The higher the CFD score, the more likely there is off-target cleavage at that site. Off-targets with a CFD score < 0.023 are not shown on this page, but are availble when following the link to the external CRISPOR tool. When compared against experimentally validated off-targets by Haeussler et al. 2016, the large majority of predicted off-targets with CFD scores < 0.023 were false-positives. Methods Relationship between predictions and experimental data Like most algorithms, the MIT specificity score is not always a perfect predictor of off-target effects. Despite low scores, many tested guides caused few and/or weak off-target cleavage when tested with whole-genome assays (Figure 2 from Haeussler et al. 2016), as shown below, and the published data contains few data points with high specificity scores. Overall though, the assays showed that the higher the specificity score, the lower the off-target effects. Similarly, efficiency scoring is not very accurate: guides with low scores can be efficient and vice versa. As a general rule, however, the higher the score, the less likely that a guide is very inefficient. The following histograms illustrate, for each type of score, how the share of inefficient guides drops with increasing efficiency scores: When reading this plot, keep in mind that both scores were evaluated on their own training data. Especially for the Moreno-Mateos score, the results are too optimistic, due to overfitting. When evaluated on independent datasets, the correlation of the prediction with other assays was around 25% lower, see Haeussler et al. 2016. At the time of writing, there is no independent dataset available yet to determine the Moreno-Mateos accuracy for each score percentile range. Track methods Exons as predicted by Ensembl Gene models were used, extended by 200 basepairs on each side, searched for the -NGG motif. Flanking 20mer guide sequences were aligned to the genome with BWA and scored with MIT Specificity scores using the command-line version of crispor.org. Non-unique guide sequences were skipped. Flanking sequences were extracted from the genome and input for Crispor efficiency scoring, available from the Crispor downloads page, which includes the Doench 2016, Moreno-Mateos 2015 and Bae 2014 algorithms, among others. Data Access The raw data can be explored interactively with the Table Browser. For automated analysis, the genome annotation is stored in a bigBed file that can be downloaded from our download server. The files for this track are called crispr.bb and crisprDetails.tab and are located in the /gbdb/danRer7/crispr directory of our downloads server. Individual regions or the whole genome annotation can be obtained using our tool bigBedToBed, which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain only features within a given range, e.g. bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg19/crisprRanges/crispr.bb -chrom=chr21 -start=0 -end=10000000 stdout The file crisprDetails.tab includes the details of the off-targets. The last column of the bigBed file is the offset of the respective line in crisprDetails.tab. E.g. if the last column is 14227033723, then the following command will extract the line with the corresponding off-target details: curl -s -r 14227033723-14227043723 http://hgdownload.soe.ucsc.edu/gbdb/hg19/crispr/crisprDetails.tab | head -n1. The off-target details can currently not be joined with the table browser. The file crisprDetails.tab is a tab-separated text file with two fields. The first field contains the numbers of off-targets for each mismatch, e.g. "0,0,1,3,49" means 0 off-targets at zero mismatches, 1 at two mismatches, 3 at three and 49 off-targets at four mismatches. The second field is a pipe-separated list of semicolon-separated tuples with the genome coordinates and the CFD score. E.g. "chr10;123376795+;42|chr5;148353274-;39" describes two off-targets, with the first at chr1:123376795 on the positive strand and a CFD score 0.42 Credits Track created by Maximilian Haeussler and Hiram Clawson, with helpful input from Jean-Paul Concordet (MNHN Paris) and Alberto Stolfi (NYU). References Haeussler M, Schönig K, Eckert H, Eschstruth A, Mianné J, Renaud JB, Schneider-Maunoury S, Shkumatava A, Teboul L, Kent J et al. Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR. Genome Biol. 2016 Jul 5;17(1):148. PMID: 27380939; PMC: PMC4934014 Bae S, Kweon J, Kim HS, Kim JS. Microhomology-based choice of Cas9 nuclease target sites. Nat Methods. 2014 Jul;11(7):705-6. PMID: 24972169 Doench JG, Fusi N, Sullender M, Hegde M, Vaimberg EW, Donovan KF, Smith I, Tothova Z, Wilen C, Orchard R et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat Biotechnol. 2016 Feb;34(2):184-91. PMID: 26780180; PMC: PMC4744125 Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. 2013 Sep;31(9):827-32. PMID: 23873081; PMC: PMC3969858 Moreno-Mateos MA, Vejnar CE, Beaudoin JD, Fernandez JP, Mis EK, Khokha MK, Giraldez AJ. CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo. Nat Methods. 2015 Oct;12(10):982-8. PMID: 26322839; PMC: PMC4589495 crispr CRISPR CRISPR/Cas9 Sp. Pyog. target sites Genes and Gene Predictions Description This track shows regions of the genome within 200 bp of transcribed regions and DNA sequences targetable by CRISPR RNA guides using the Cas9 enzyme from S. pyogenes (PAM: NGG). CRISPR target sites were annotated with predicted specificity (off-target effects) and predicted efficiency (on-target cleavage) by various algorithms through the tool CRISPOR. Display Conventions and Configuration The track "CRISPR Regions" shows the regions of the genome where target sites were analyzed, i.e. within 200 bp of transcribed regions as annotated by Ensembl transcript models. The track "CRISPR Targets" shows the target sites in these regions. The target sequence of the guide is shown with a thick (exon) bar. The PAM motif match (NGG) is shown with a thinner bar. Guides are colored to reflect both predicted specificity and efficiency. Specificity reflects the "uniqueness" of a 20mer sequence in the genome; the less unique a sequence is, the more likely it is to cleave other locations of the genome (off-target effects). Efficiency is the frequency of cleavage at the target site (on-target efficiency). Shades of gray stand for sites that are hard to target specifically, as the 20mer is not very unique in the genome: impossible to target: target site has at least one identical copy in the genome and was not scored hard to target: many similar sequences in the genome that alignment stopped, repeat? hard to target: target site was aligned but results in a low specificity score <= 50 (see below) Colors highlight targets that are specific in the genome (MIT specificity > 50) but have different predicted efficiencies: unable to calculate Doench/Fusi 2016 efficiency score low predicted cleavage: Doench/Fusi 2016 Efficiency percentile <= 30 medium predicted cleavage: Doench/Fusi 2016 Efficiency percentile > 30 and < 55 high predicted cleavage: Doench/Fusi 2016 Efficiency > 55 Mouse-over a target site to show predicted specificity and efficiency scores: The MIT Specificity score summarizes all off-targets into a single number from 0-100. The higher the number, the fewer off-target effects are expected. We recommend guides with an MIT specificity > 50. The efficiency score tries to predict if a guide leads to rather strong or weak cleavage. According to (Haeussler et al. 2016), the Doench 2016 Efficiency score should be used to select the guide with the highest cleavage efficiency when expressing guides from RNA PolIII Promoters such as U6. Scores are given as percentiles, e.g. "70%" means that 70% of mammalian guides have a score equal or lower than this guide. The raw score number is also shown in parentheses after the percentile. The Moreno-Mateos 2015 Efficiency score should be used instead of the Doench 2016 score when transcribing the guide in vitro with a T7 promoter, e.g. for injections in mouse, zebrafish or Xenopus embryos. The Moreno-Mateos score is given in percentiles and the raw value in parentheses, see the note above. Click onto features to show all scores and predicted off-targets with up to four mismatches. The Out-of-Frame score by Bae et al. 2014 is correlated with the probability that mutations induced by the guide RNA will disrupt the open reading frame. The authors recommend out-of-frame scores > 66 to create knock-outs with a single guide efficiently. Off-target sites are sorted by the CFD (Cutting Frequency Determination) score (Doench et al. 2016). The higher the CFD score, the more likely there is off-target cleavage at that site. Off-targets with a CFD score < 0.023 are not shown on this page, but are availble when following the link to the external CRISPOR tool. When compared against experimentally validated off-targets by Haeussler et al. 2016, the large majority of predicted off-targets with CFD scores < 0.023 were false-positives. Methods Relationship between predictions and experimental data Like most algorithms, the MIT specificity score is not always a perfect predictor of off-target effects. Despite low scores, many tested guides caused few and/or weak off-target cleavage when tested with whole-genome assays (Figure 2 from Haeussler et al. 2016), as shown below, and the published data contains few data points with high specificity scores. Overall though, the assays showed that the higher the specificity score, the lower the off-target effects. Similarly, efficiency scoring is not very accurate: guides with low scores can be efficient and vice versa. As a general rule, however, the higher the score, the less likely that a guide is very inefficient. The following histograms illustrate, for each type of score, how the share of inefficient guides drops with increasing efficiency scores: When reading this plot, keep in mind that both scores were evaluated on their own training data. Especially for the Moreno-Mateos score, the results are too optimistic, due to overfitting. When evaluated on independent datasets, the correlation of the prediction with other assays was around 25% lower, see Haeussler et al. 2016. At the time of writing, there is no independent dataset available yet to determine the Moreno-Mateos accuracy for each score percentile range. Track methods Exons as predicted by Ensembl Gene models were used, extended by 200 basepairs on each side, searched for the -NGG motif. Flanking 20mer guide sequences were aligned to the genome with BWA and scored with MIT Specificity scores using the command-line version of crispor.org. Non-unique guide sequences were skipped. Flanking sequences were extracted from the genome and input for Crispor efficiency scoring, available from the Crispor downloads page, which includes the Doench 2016, Moreno-Mateos 2015 and Bae 2014 algorithms, among others. Data Access The raw data can be explored interactively with the Table Browser. For automated analysis, the genome annotation is stored in a bigBed file that can be downloaded from our download server. The files for this track are called crispr.bb and crisprDetails.tab and are located in the /gbdb/danRer7/crispr directory of our downloads server. Individual regions or the whole genome annotation can be obtained using our tool bigBedToBed, which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain only features within a given range, e.g. bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg19/crispr/crispr.bb -chrom=chr21 -start=0 -end=10000000 stdout The file crisprDetails.tab includes the details of the off-targets. The last column of the bigBed file is the offset of the respective line in crisprDetails.tab. E.g. if the last column is 14227033723, then the following command will extract the line with the corresponding off-target details: curl -s -r 14227033723-14227043723 http://hgdownload.soe.ucsc.edu/gbdb/hg19/crispr/crisprDetails.tab | head -n1. The off-target details can currently not be joined with the table browser. The file crisprDetails.tab is a tab-separated text file with two fields. The first field contains the numbers of off-targets for each mismatch, e.g. "0,0,1,3,49" means 0 off-targets at zero mismatches, 1 at two mismatches, 3 at three and 49 off-targets at four mismatches. The second field is a pipe-separated list of semicolon-separated tuples with the genome coordinates and the CFD score. E.g. "chr10;123376795+;42|chr5;148353274-;39" describes two off-targets, with the first at chr1:123376795 on the positive strand and a CFD score 0.42 Credits Track created by Maximilian Haeussler and Hiram Clawson, with helpful input from Jean-Paul Concordet (MNHN Paris) and Alberto Stolfi (NYU). References Haeussler M, Schönig K, Eckert H, Eschstruth A, Mianné J, Renaud JB, Schneider-Maunoury S, Shkumatava A, Teboul L, Kent J et al. Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR. Genome Biol. 2016 Jul 5;17(1):148. PMID: 27380939; PMC: PMC4934014 Bae S, Kweon J, Kim HS, Kim JS. Microhomology-based choice of Cas9 nuclease target sites. Nat Methods. 2014 Jul;11(7):705-6. PMID: 24972169 Doench JG, Fusi N, Sullender M, Hegde M, Vaimberg EW, Donovan KF, Smith I, Tothova Z, Wilen C, Orchard R et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat Biotechnol. 2016 Feb;34(2):184-91. PMID: 26780180; PMC: PMC4744125 Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. 2013 Sep;31(9):827-32. PMID: 23873081; PMC: PMC3969858 Moreno-Mateos MA, Vejnar CE, Beaudoin JD, Fernandez JP, Mis EK, Khokha MK, Giraldez AJ. CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo. Nat Methods. 2015 Oct;12(10):982-8. PMID: 26322839; PMC: PMC4589495 crisprTargets CRISPR Targets CRISPR/Cas9 -NGG Targets Genes and Gene Predictions Description This track shows regions of the genome within 200 bp of transcribed regions and DNA sequences targetable by CRISPR RNA guides using the Cas9 enzyme from S. pyogenes (PAM: NGG). CRISPR target sites were annotated with predicted specificity (off-target effects) and predicted efficiency (on-target cleavage) by various algorithms through the tool CRISPOR. Display Conventions and Configuration The track "CRISPR Regions" shows the regions of the genome where target sites were analyzed, i.e. within 200 bp of transcribed regions as annotated by Ensembl transcript models. The track "CRISPR Targets" shows the target sites in these regions. The target sequence of the guide is shown with a thick (exon) bar. The PAM motif match (NGG) is shown with a thinner bar. Guides are colored to reflect both predicted specificity and efficiency. Specificity reflects the "uniqueness" of a 20mer sequence in the genome; the less unique a sequence is, the more likely it is to cleave other locations of the genome (off-target effects). Efficiency is the frequency of cleavage at the target site (on-target efficiency). Shades of gray stand for sites that are hard to target specifically, as the 20mer is not very unique in the genome: impossible to target: target site has at least one identical copy in the genome and was not scored hard to target: many similar sequences in the genome that alignment stopped, repeat? hard to target: target site was aligned but results in a low specificity score <= 50 (see below) Colors highlight targets that are specific in the genome (MIT specificity > 50) but have different predicted efficiencies: unable to calculate Doench/Fusi 2016 efficiency score low predicted cleavage: Doench/Fusi 2016 Efficiency percentile <= 30 medium predicted cleavage: Doench/Fusi 2016 Efficiency percentile > 30 and < 55 high predicted cleavage: Doench/Fusi 2016 Efficiency > 55 Mouse-over a target site to show predicted specificity and efficiency scores: The MIT Specificity score summarizes all off-targets into a single number from 0-100. The higher the number, the fewer off-target effects are expected. We recommend guides with an MIT specificity > 50. The efficiency score tries to predict if a guide leads to rather strong or weak cleavage. According to (Haeussler et al. 2016), the Doench 2016 Efficiency score should be used to select the guide with the highest cleavage efficiency when expressing guides from RNA PolIII Promoters such as U6. Scores are given as percentiles, e.g. "70%" means that 70% of mammalian guides have a score equal or lower than this guide. The raw score number is also shown in parentheses after the percentile. The Moreno-Mateos 2015 Efficiency score should be used instead of the Doench 2016 score when transcribing the guide in vitro with a T7 promoter, e.g. for injections in mouse, zebrafish or Xenopus embryos. The Moreno-Mateos score is given in percentiles and the raw value in parentheses, see the note above. Click onto features to show all scores and predicted off-targets with up to four mismatches. The Out-of-Frame score by Bae et al. 2014 is correlated with the probability that mutations induced by the guide RNA will disrupt the open reading frame. The authors recommend out-of-frame scores > 66 to create knock-outs with a single guide efficiently. Off-target sites are sorted by the CFD (Cutting Frequency Determination) score (Doench et al. 2016). The higher the CFD score, the more likely there is off-target cleavage at that site. Off-targets with a CFD score < 0.023 are not shown on this page, but are availble when following the link to the external CRISPOR tool. When compared against experimentally validated off-targets by Haeussler et al. 2016, the large majority of predicted off-targets with CFD scores < 0.023 were false-positives. Methods Relationship between predictions and experimental data Like most algorithms, the MIT specificity score is not always a perfect predictor of off-target effects. Despite low scores, many tested guides caused few and/or weak off-target cleavage when tested with whole-genome assays (Figure 2 from Haeussler et al. 2016), as shown below, and the published data contains few data points with high specificity scores. Overall though, the assays showed that the higher the specificity score, the lower the off-target effects. Similarly, efficiency scoring is not very accurate: guides with low scores can be efficient and vice versa. As a general rule, however, the higher the score, the less likely that a guide is very inefficient. The following histograms illustrate, for each type of score, how the share of inefficient guides drops with increasing efficiency scores: When reading this plot, keep in mind that both scores were evaluated on their own training data. Especially for the Moreno-Mateos score, the results are too optimistic, due to overfitting. When evaluated on independent datasets, the correlation of the prediction with other assays was around 25% lower, see Haeussler et al. 2016. At the time of writing, there is no independent dataset available yet to determine the Moreno-Mateos accuracy for each score percentile range. Track methods Exons as predicted by Ensembl Gene models were used, extended by 200 basepairs on each side, searched for the -NGG motif. Flanking 20mer guide sequences were aligned to the genome with BWA and scored with MIT Specificity scores using the command-line version of crispor.org. Non-unique guide sequences were skipped. Flanking sequences were extracted from the genome and input for Crispor efficiency scoring, available from the Crispor downloads page, which includes the Doench 2016, Moreno-Mateos 2015 and Bae 2014 algorithms, among others. Data Access The raw data can be explored interactively with the Table Browser. For automated analysis, the genome annotation is stored in a bigBed file that can be downloaded from our download server. The files for this track are called crispr.bb and crisprDetails.tab and are located in the /gbdb/danRer7/crispr directory of our downloads server. Individual regions or the whole genome annotation can be obtained using our tool bigBedToBed, which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain only features within a given range, e.g. bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg19/crisprTargets/crispr.bb -chrom=chr21 -start=0 -end=10000000 stdout The file crisprDetails.tab includes the details of the off-targets. The last column of the bigBed file is the offset of the respective line in crisprDetails.tab. E.g. if the last column is 14227033723, then the following command will extract the line with the corresponding off-target details: curl -s -r 14227033723-14227043723 http://hgdownload.soe.ucsc.edu/gbdb/hg19/crispr/crisprDetails.tab | head -n1. The off-target details can currently not be joined with the table browser. The file crisprDetails.tab is a tab-separated text file with two fields. The first field contains the numbers of off-targets for each mismatch, e.g. "0,0,1,3,49" means 0 off-targets at zero mismatches, 1 at two mismatches, 3 at three and 49 off-targets at four mismatches. The second field is a pipe-separated list of semicolon-separated tuples with the genome coordinates and the CFD score. E.g. "chr10;123376795+;42|chr5;148353274-;39" describes two off-targets, with the first at chr1:123376795 on the positive strand and a CFD score 0.42 Credits Track created by Maximilian Haeussler and Hiram Clawson, with helpful input from Jean-Paul Concordet (MNHN Paris) and Alberto Stolfi (NYU). References Haeussler M, Schönig K, Eckert H, Eschstruth A, Mianné J, Renaud JB, Schneider-Maunoury S, Shkumatava A, Teboul L, Kent J et al. Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR. Genome Biol. 2016 Jul 5;17(1):148. PMID: 27380939; PMC: PMC4934014 Bae S, Kweon J, Kim HS, Kim JS. Microhomology-based choice of Cas9 nuclease target sites. Nat Methods. 2014 Jul;11(7):705-6. PMID: 24972169 Doench JG, Fusi N, Sullender M, Hegde M, Vaimberg EW, Donovan KF, Smith I, Tothova Z, Wilen C, Orchard R et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat Biotechnol. 2016 Feb;34(2):184-91. PMID: 26780180; PMC: PMC4744125 Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. 2013 Sep;31(9):827-32. PMID: 23873081; PMC: PMC3969858 Moreno-Mateos MA, Vejnar CE, Beaudoin JD, Fernandez JP, Mis EK, Khokha MK, Giraldez AJ. CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo. Nat Methods. 2015 Oct;12(10):982-8. PMID: 26322839; PMC: PMC4589495 ensGene Ensembl Genes Ensembl Genes Genes and Gene Predictions Description These gene predictions were generated by Ensembl. For more information on the different gene tracks, see our Genes FAQ. Methods For a description of the methods used in Ensembl gene predictions, please refer to Hubbard et al. (2002), also listed in the References section below. Data access Ensembl Gene data can be explored interactively using the Table Browser or the Data Integrator. For local downloads, the genePred format files for danRer7 are available in our downloads directory as ensGene.txt.gz or in our genes download directory in GTF format. For programmatic access, the data can be queried from the REST API or directly from our public MySQL servers. Instructions on this method are available on our MySQL help page and on our blog. Previous versions of this track can be found on our archive download server. Credits We would like to thank Ensembl for providing these gene annotations. For more information, please see Ensembl's genome annotation page. References Hubbard T, Barker D, Birney E, Cameron G, Chen Y, Clark L, Cox T, Cuff J, Curwen V, Down T et al. The Ensembl genome database project. Nucleic Acids Res. 2002 Jan 1;30(1):38-41. PMID: 11752248; PMC: PMC99161 evaSnp4 EVA SNP Release 4 Short Genetic Variants from European Variant Archive Release 4 Variation and Repeats Description This track contains mappings of single nucleotide variants and small insertions and deletions (indels) from the European Variation Archive (EVA) Release 4 for the zebrafish danRer7 genome. The dbSNP database at NCBI no longer hosts non-human variants. Interpreting and Configuring the Graphical Display Variants are shown as single tick marks at most zoom levels. When viewing the track at or near base-level resolution, the displayed width of the SNP variant corresponds to the width of the variant in the reference sequence. Insertions are indicated by a single tick mark displayed between two nucleotides, single nucleotide polymorphisms are displayed as the width of a single base, and multiple nucleotide variants are represented by a block that spans two or more bases. The display is set to automatically collapse to dense visibility when there are more than 100k variants in the window. When the window size is more than 250k bp, the display is switched to density graph mode. Searching, details, and filtering Navigation to an individual variant can be accomplished by typing or copying the variant identifier (rsID) or the genomic coordinates into the Position/Search box on the Browser. A click on an item in the graphical display displays a page with data about that variant. Data fields include the Reference and Alternate Alleles, the class of the variant as reported by EVA, the source of the data, the amino acid change, if any, and the functional class as determined by UCSC's Variant Annotation Integrator. Variants can be filtered using the track controls to show subsets of the data by either EVA Sequence Ontology (SO) term, UCSC-generated functional effect, or by color, which bins the UCSC functional effects into general classes. Mouse-over Mousing over an item shows the ucscClass, which is the consequence according to the Variant Annotation Integrator, and the aaChange when one is available, which is the change in amino acid in HGVS.p terms. Items may have multiple ucscClasses, which will all be shown in the mouse-over in a comma-separated list. Likewise, multiple HGVS.p terms may be shown for each rsID separated by spaces describing all possible AA changes. Multiple items may appear due to different variant predictions on multiple gene transcripts. For all organisms the gene models used were the NCBI RefSeq curated when available, if not then ensembl genes, or finally UCSC mappings of RefSeq if neither of the previous models was possible. Track colors Variants are colored according to the most potentially deleterious functional effect prediction according to the Variant Annotation Integrator. Specific bins can be seen in the Methods section below. Color Variant Type Protein-altering variants and splice site variants Synonymous codon variants Non-coding transcript or Untranslated Region (UTR) variants Intergenic and intronic variants Sequence ontology (SO) Variants are classified by EVA into one of the following sequence ontology terms: substitution — A single nucleotide in the reference is replaced by another, alternate allele deletion — One or more nucleotides is deleted. The representation in the database is to display one additional nucleotide in both the Reference field (Ref) and the Alternate Allele field (Alt). E.g. a variant that is a deletion of an A maybe be represented as Ref = GA and Alt = G. insertion — One or more nucleotides is inserted. The representation in the database is to display one additional nucleotide in both the Reference field (Ref) and the Alternate Allele field (Alt). E.g. a variant that is an insertion of a T maybe be represented as Ref = G and Alt = GT delins — Similar to tandemRepeat, in that the runs of Ref and Alt Alleles are of different length, except that there is more than one type of nucleotide, e.g., Ref = CCAAAAACAAAAACA, Alt = ACAAAAAC. multipleNucleotideVariant — More than one nucleotide is substituted by an equal number of different nucleotides, e.g., Ref = AA, Alt = GC. sequence alteration — A parent term meant to signify a deviation from another sequence. Can be assigned to variants that have not been characterized yet. Methods Data were downloaded from the European Variation Archive EVA release 4 (2022-11-21) current_ids.vcf.gz files corresponding to the proper assembly. Chromosome names were converted to UCSC-style and the variants passed through the Variant Annotation Integrator to predict consequence. For every organism the NCBI RefSeq curated models were used when available, followed by ensembl genes, and finally UCSC mapping of RefSeq when neither of the previous models were possible. Variants were then colored according to their predicted consequence in the following fashion: Protein-altering variants and splice site variants - exon_loss_variant, frameshift_variant, inframe_deletion, inframe_insertion, initiator_codon_variant, missense_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, stop_gained, stop_lost, coding_sequence_variant, transcript_ablation Synonymous codon variants - synonymous_variant, stop_retained_variant Non-coding transcript or Untranslated Region (UTR) variants - 5_prime_UTR_variant, 3_prime_UTR_variant, complex_transcript_variant, non_coding_transcript_exon_variant Intergenic and intronic variants - upstream_gene_variant, downstream_gene_variant, intron_variant, intergenic_variant, NMD_transcript_variant, no_sequence_alteration Sequence Ontology ("SO:") terms were converted to the variant classes, then the files were converted to BED, and then bigBed format. No functional annotations were provided by the EVA (e.g., missense, nonsense, etc). These were computed using UCSC's Variant Annotation Integrator (Hinrichs, et al., 2016). Amino-acid substitutions for missense variants are based on RefSeq alignments of mRNA transcripts, which do not always match the amino acids predicted from translating the genomic sequence. Therefore, in some instances, the variant and the genomic nucleotide and associated amino acid may be reversed. E.g., a Pro > Arg change from the perspective of the mRNA would be Arg > Pro from the persepective the genomic sequence. Also, in bosTau9, galGal5, rheMac8, danRer10 and danRer11 the mitochondrial sequence was removed or renamed to match UCSC. For complete documentation of the processing of these tracks, read the EVA Release 4 MakeDoc. Data Access Note: It is not recommeneded to use LiftOver to convert SNPs between assemblies, and more information about how to convert SNPs between assemblies can be found on the following FAQ entry. The data can be explored interactively with the Table Browser, or the Data Integrator. For automated analysis, the data may be queried from our REST API. Please refer to our mailing list archives for questions, or our Data Access FAQ for more information. For automated download and analysis, this annotation is stored in a bigBed file that can be downloaded from our download server. The file for this track is called evaSnp4.bb. Individual regions or the whole genome annotation can be obtained using our tool bigBedToBed which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain only features within a given range, e.g. bigBedToBed https://hgdownload.soe.ucsc.edu/gbdb/danRer7/bbi/evaSnp4.bb -chrom=chr21 -start=0 -end=100000000 stdout Credits This track was produced from the European Variation Archive release 4 data. Consequences were predicted using UCSC's Variant Annotation Integrator and NCBI's RefSeq as well as ensembl gene models. References Cezard T, Cunningham F, Hunt SE, Koylass B, Kumar N, Saunders G, Shen A, Silva AF, Tsukanov K, Venkataraman S et al. The European Variation Archive: a FAIR resource of genomic variation for all species. Nucleic Acids Res. 2021 Oct 28:gkab960. doi:10.1093/nar/gkab960. Epub ahead of print. PMID: 34718739. PMID: PMC8728205. Hinrichs AS, Raney BJ, Speir ML, Rhead B, Casper J, Karolchik D, Kuhn RM, Rosenbloom KR, Zweig AS, Haussler D, Kent WJ. UCSC Data Integrator and Variant Annotation Integrator. Bioinformatics. 2016 May 1;32(9):1430-2. PMID: 26740527; PMC: PMC4848401 evaSnp5 EVA SNP Release 5 Short Genetic Variants from European Variant Archive Release 5 Variation and Repeats Description This track contains mappings of single nucleotide variants and small insertions and deletions (indels) from the European Variation Archive (EVA) Release 5 for the zebrafish danRer7 genome. The dbSNP database at NCBI no longer hosts non-human variants. Interpreting and Configuring the Graphical Display Variants are shown as single tick marks at most zoom levels. When viewing the track at or near base-level resolution, the displayed width of the SNP variant corresponds to the width of the variant in the reference sequence. Insertions are indicated by a single tick mark displayed between two nucleotides, single nucleotide polymorphisms are displayed as the width of a single base, and multiple nucleotide variants are represented by a block that spans two or more bases. The display is set to automatically collapse to dense visibility when there are more than 100k variants in the window. When the window size is more than 250k bp, the display is switched to density graph mode. Searching, details, and filtering Navigation to an individual variant can be accomplished by typing or copying the variant identifier (rsID) or the genomic coordinates into the Position/Search box on the Browser. A click on an item in the graphical display displays a page with data about that variant. Data fields include the Reference and Alternate Alleles, the class of the variant as reported by EVA, the source of the data, the amino acid change, if any, and the functional class as determined by UCSC's Variant Annotation Integrator. Variants can be filtered using the track controls to show subsets of the data by either EVA Sequence Ontology (SO) term, UCSC-generated functional effect, or by color, which bins the UCSC functional effects into general classes. Mouse-over Mousing over an item shows the ucscClass, which is the consequence according to the Variant Annotation Integrator, and the aaChange when one is available, which is the change in amino acid in HGVS.p terms. Items may have multiple ucscClasses, which will all be shown in the mouse-over in a comma-separated list. Likewise, multiple HGVS.p terms may be shown for each rsID separated by spaces describing all possible AA changes. Multiple items may appear due to different variant predictions on multiple gene transcripts. For all organisms the gene models used were the NCBI RefSeq curated when available, if not then ensembl genes, or finally UCSC mappings of RefSeq if neither of the previous models was possible. Track colors Variants are colored according to the most potentially deleterious functional effect prediction according to the Variant Annotation Integrator. Specific bins can be seen in the Methods section below. Color Variant Type Protein-altering variants and splice site variants Synonymous codon variants Non-coding transcript or Untranslated Region (UTR) variants Intergenic and intronic variants Sequence ontology (SO) Variants are classified by EVA into one of the following sequence ontology terms: substitution — A single nucleotide in the reference is replaced by another, alternate allele deletion — One or more nucleotides is deleted. The representation in the database is to display one additional nucleotide in both the Reference field (Ref) and the Alternate Allele field (Alt). E.g. a variant that is a deletion of an A maybe be represented as Ref = GA and Alt = G. insertion — One or more nucleotides is inserted. The representation in the database is to display one additional nucleotide in both the Reference field (Ref) and the Alternate Allele field (Alt). E.g. a variant that is an insertion of a T maybe be represented as Ref = G and Alt = GT delins — Similar to tandemRepeat, in that the runs of Ref and Alt Alleles are of different length, except that there is more than one type of nucleotide, e.g., Ref = CCAAAAACAAAAACA, Alt = ACAAAAAC. multipleNucleotideVariant — More than one nucleotide is substituted by an equal number of different nucleotides, e.g., Ref = AA, Alt = GC. sequence alteration — A parent term meant to signify a deviation from another sequence. Can be assigned to variants that have not been characterized yet. Methods Data were downloaded from the European Variation Archive EVA release 5 (2023-9-7) current_ids.vcf.gz files corresponding to the proper assembly. Chromosome names were converted to UCSC-style and the variants passed through the Variant Annotation Integrator to predict consequence. For every organism the NCBI RefSeq curated models were used when available, followed by ensembl genes, and finally UCSC mapping of RefSeq when neither of the previous models were possible. Variants were then colored according to their predicted consequence in the following fashion: Protein-altering variants and splice site variants - exon_loss_variant, frameshift_variant, inframe_deletion, inframe_insertion, initiator_codon_variant, missense_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, stop_gained, stop_lost, coding_sequence_variant, transcript_ablation Synonymous codon variants - synonymous_variant, stop_retained_variant Non-coding transcript or Untranslated Region (UTR) variants - 5_prime_UTR_variant, 3_prime_UTR_variant, complex_transcript_variant, non_coding_transcript_exon_variant Intergenic and intronic variants - upstream_gene_variant, downstream_gene_variant, intron_variant, intergenic_variant, NMD_transcript_variant, no_sequence_alteration Sequence Ontology ("SO:") terms were converted to the variant classes, then the files were converted to BED, and then bigBed format. No functional annotations were provided by the EVA (e.g., missense, nonsense, etc). These were computed using UCSC's Variant Annotation Integrator (Hinrichs, et al., 2016). Amino-acid substitutions for missense variants are based on RefSeq alignments of mRNA transcripts, which do not always match the amino acids predicted from translating the genomic sequence. Therefore, in some instances, the variant and the genomic nucleotide and associated amino acid may be reversed. E.g., a Pro > Arg change from the perspective of the mRNA would be Arg > Pro from the persepective the genomic sequence. Also, in bosTau9, galGal5, rheMac8, danRer10 and danRer11 the mitochondrial sequence was removed or renamed to match UCSC. For complete documentation of the processing of these tracks, read the EVA Release 5 MakeDoc. Data Access Note: It is not recommeneded to use LiftOver to convert SNPs between assemblies, and more information about how to convert SNPs between assemblies can be found on the following FAQ entry. The data can be explored interactively with the Table Browser, or the Data Integrator. For automated analysis, the data may be queried from our REST API. Please refer to our mailing list archives for questions, or our Data Access FAQ for more information. For automated download and analysis, this annotation is stored in a bigBed file that can be downloaded from our download server. The file for this track is called evaSnp5.bb. Individual regions or the whole genome annotation can be obtained using our tool bigBedToBed which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain only features within a given range, e.g. bigBedToBed https://hgdownload.soe.ucsc.edu/gbdb/danRer7/bbi/evaSnp5.bb -chrom=chr21 -start=0 -end=100000000 stdout Credits This track was produced from the European Variation Archive release 5 data. Consequences were predicted using UCSC's Variant Annotation Integrator and NCBI's RefSeq as well as ensembl gene models. References Cezard T, Cunningham F, Hunt SE, Koylass B, Kumar N, Saunders G, Shen A, Silva AF, Tsukanov K, Venkataraman S et al. The European Variation Archive: a FAIR resource of genomic variation for all species. Nucleic Acids Res. 2021 Oct 28:gkab960. doi:10.1093/nar/gkab960. Epub ahead of print. PMID: 34718739. PMID: PMC8728205. Hinrichs AS, Raney BJ, Speir ML, Rhead B, Casper J, Karolchik D, Kuhn RM, Rosenbloom KR, Zweig AS, Haussler D, Kent WJ. UCSC Data Integrator and Variant Annotation Integrator. Bioinformatics. 2016 May 1;32(9):1430-2. PMID: 26740527; PMC: PMC4848401 gap Gap Gap Locations Mapping and Sequencing Description This track depicts gaps in the draft assembly (Jul. 2010, Wellcome Trust Sanger Institute Zv9 (GCA_000002035.2)) of the zebrafish genome. Gaps are represented as black boxes in this track. If the relative order and orientation of the contigs on either side of the gap is supported by read pair data, it is a bridged gap and a white line is drawn through the black box representing the gap. This assembly contains the following principal types of gaps: fragment - gaps between the Whole Genome Shotgun contigs of a supercontig. (In this context, a contig is a set of overlapping sequence reads. A supercontig is a set of contigs ordered and oriented during the Whole Genome Shotgun process using paired-end reads.) These are represented by 100 Ns in the assembly. contig - gaps between supercontigs not linked by the fingerprint map, but instead by marker data. (In this context, the "Contig" gap type refers to a map contig, not a sequence contig.) These are represented by 100 Ns in the assembly for all chromosomes. gc5BaseBw GC Percent GC Percent in 5-Base Windows Mapping and Sequencing Description The GC percent track shows the percentage of G (guanine) and C (cytosine) bases in 5-base windows. High GC content is typically associated with gene-rich areas. This track may be configured in a variety of ways to highlight different apsects of the displayed information. Click the "Graph configuration help" link for an explanation of the configuration options. Credits The data and presentation of this graph were prepared by Hiram Clawson. genscan Genscan Genes Genscan Gene Predictions Genes and Gene Predictions Description This track shows predictions from the Genscan program written by Chris Burge. The predictions are based on transcriptional, translational and donor/acceptor splicing signals as well as the length and compositional distributions of exons, introns and intergenic regions. For more information on the different gene tracks, see our Genes FAQ. Display Conventions and Configuration This track follows the display conventions for gene prediction tracks. The track description page offers the following filter and configuration options: Color track by codons: Select the genomic codons option to color and label each codon in a zoomed-in display to facilitate validation and comparison of gene predictions. Go to the Coloring Gene Predictions and Annotations by Codon page for more information about this feature. Methods For a description of the Genscan program and the model that underlies it, refer to Burge and Karlin (1997) in the References section below. The splice site models used are described in more detail in Burge (1998) below. Credits Thanks to Chris Burge for providing the Genscan program. References Burge C. Modeling Dependencies in Pre-mRNA Splicing Signals. In: Salzberg S, Searls D, Kasif S, editors. Computational Methods in Molecular Biology. Amsterdam: Elsevier Science; 1998. p. 127-163. Burge C, Karlin S. Prediction of complete gene structures in human genomic DNA. J. Mol. Biol. 1997 Apr 25;268(1):78-94. PMID: 9149143 grcIncidentDb GRC Incident GRC Incident Database Mapping and Sequencing Description This track shows locations in the zebrafish assembly where assembly problems have been noted or resolved, as reported by the Genome Reference Consortium (GRC). If you would like to report an assembly problem, please use the GRC issue reporting system. Methods Data for this track are extracted from the GRC incident database from the specific species *_issues.gff3 file. The track is synchronized once daily to incorporate new updates. Credits The data and presentation of this track were prepared by Hiram Clawson. blastHg18KG Human Proteins Human Proteins Mapped by Chained tBLASTn Genes and Gene Predictions Description This track contains tBLASTn alignments of the peptides from the predicted and known genes identified in the hg18 UCSC Genes track. Methods First, the predicted proteins from the human UCSC Genes track were aligned with the human genome using the Blat program to discover exon boundaries. Next, the amino acid sequences that make up each exon were aligned with the zebrafish sequence using the tBLASTn program. Finally, the putative zebrafish exons were chained together using an organism-specific maximum gap size but no gap penalty. The single best exon chains extending over more than 60% of the query protein were included. Exon chains that extended over 60% of the query and matched at least 60% of the protein's amino acids were also included. Credits tBLASTn is part of the NCBI BLAST tool set. For more information on BLAST, see Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403-410. Blat was written by Jim Kent. The remaining utilities used to produce this track were written by Jim Kent or Brian Raney. ucscToINSDC INSDC Accession at INSDC - International Nucleotide Sequence Database Collaboration Mapping and Sequencing Description This track associates UCSC Genome Browser chromosome names to accession names from the International Nucleotide Sequence Database Collaboration (INSDC). The data were downloaded from the NCBI assembly database. Credits The data for this track was prepared by Hiram Clawson. nestedRepeats Interrupted Rpts Fragments of Interrupted Repeats Joined by RepeatMasker ID Variation and Repeats Description This track shows joined fragments of interrupted repeats extracted from the output of the RepeatMasker program which screens DNA sequences for interspersed repeats and low complexity DNA sequences using the Repbase Update library of repeats from the Genetic Information Research Institute (GIRI). Repbase Update is described in Jurka (2000) in the References section below. The detailed annotations from RepeatMasker are in the RepeatMasker track. This track shows fragments of original repeat insertions which have been interrupted by insertions of younger repeats or through local rearrangements. The fragments are joined using the ID column of RepeatMasker output. Display Conventions and Configuration In pack or full mode, each interrupted repeat is displayed as boxes (fragments) joined by horizontal lines, labeled with the repeat name. If all fragments are on the same strand, arrows are added to the horizontal line to indicate the strand. In dense or squish mode, labels and arrows are omitted and in dense mode, all items are collapsed to fit on a single row. Items are shaded according to the average identity score of their fragments. Usually, the shade of an item is similar to the shades of its fragments unless some fragments are much more diverged than others. The score displayed above is the average identity score, clipped to a range of 50% - 100% and then mapped to the range 0 - 1000 for shading in the browser. Methods UCSC has used the most current versions of the RepeatMasker software and repeat libraries available to generate these data. Note that these versions may be newer than those that are publicly available on the Internet. Data are generated using the RepeatMasker -s flag. Additional flags may be used for certain organisms. See the FAQ for more information. Credits Thanks to Arian Smit, Robert Hubley and GIRI for providing the tools and repeat libraries used to generate this track. References Smit AFA, Hubley R, Green P. RepeatMasker Open-3.0. http://www.repeatmasker.org. 1996-2010. Repbase Update is described in: Jurka J. Repbase Update: a database and an electronic journal of repetitive elements. Trends Genet. 2000 Sep;16(9):418-420. PMID: 10973072 For a discussion of repeats in mammalian genomes, see: Smit AF. Interspersed repeats and other mementos of transposable elements in mammalian genomes. Curr Opin Genet Dev. 1999 Dec;9(6):657-63. PMID: 10607616 Smit AF. The origin of interspersed repeats in the human genome. Curr Opin Genet Dev. 1996 Dec;6(6):743-8. PMID: 8994846 microsat Microsatellite Microsatellites - Di-nucleotide and Tri-nucleotide Repeats Variation and Repeats Description This track displays regions that are likely to be useful as microsatellite markers. These are sequences of at least 15 perfect di-nucleotide and tri-nucleotide repeats and tend to be highly polymorphic in the population. Methods The data shown in this track are a subset of the Simple Repeats track, selecting only those repeats of period 2 and 3, with 100% identity and no indels and with at least 15 copies of the repeat. The Simple Repeats track is created using the Tandem Repeats Finder. For more information about this program, see Benson (1999). Credits Tandem Repeats Finder was written by Gary Benson. References Benson G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res. 1999 Jan 15;27(2):573-80. PMID: 9862982; PMC: PMC148217 xenoMrna Other mRNAs Non-Zebrafish mRNAs from GenBank mRNA and EST Description This track displays translated blat alignments of vertebrate and invertebrate mRNA in GenBank from organisms other than zebrafish. Display Conventions and Configuration This track follows the display conventions for PSL alignment tracks. In dense display mode, the items that are more darkly shaded indicate matches of better quality. The strand information (+/-) for this track is in two parts. The first + indicates the orientation of the query sequence whose translated protein produced the match (here always 5' to 3', hence +). The second + or - indicates the orientation of the matching translated genomic sequence. Because the two orientations of a DNA sequence give different predicted protein sequences, there are four combinations. ++ is not the same as --, nor is +- the same as -+. The description page for this track has a filter that can be used to change the display mode, alter the color, and include/exclude a subset of items within the track. This may be helpful when many items are shown in the track display, especially when only some are relevant to the current task. To use the filter: Type a term in one or more of the text boxes to filter the mRNA display. For example, to apply the filter to all mRNAs expressed in a specific organ, type the name of the organ in the tissue box. To view the list of valid terms for each text box, consult the table in the Table Browser that corresponds to the factor on which you wish to filter. For example, the "tissue" table contains all the types of tissues that can be entered into the tissue text box. Multiple terms may be entered at once, separated by a space. Wildcards may also be used in the filter. If filtering on more than one value, choose the desired combination logic. If "and" is selected, only mRNAs that match all filter criteria will be highlighted. If "or" is selected, mRNAs that match any one of the filter criteria will be highlighted. Choose the color or display characteristic that should be used to highlight or include/exclude the filtered items. If "exclude" is chosen, the browser will not display mRNAs that match the filter criteria. If "include" is selected, the browser will display only those mRNAs that match the filter criteria. This track may also be configured to display codon coloring, a feature that allows the user to quickly compare mRNAs against the genomic sequence. For more information about this option, go to the Codon and Base Coloring for Alignment Tracks page. Several types of alignment gap may also be colored; for more information, go to the Alignment Insertion/Deletion Display Options page. Methods The mRNAs were aligned against the zebrafish genome using translated blat. When a single mRNA aligned in multiple places, the alignment having the highest base identity was found. Only those alignments having a base identity level within 1% of the best and at least 25% base identity with the genomic sequence were kept. Credits The mRNA track was produced at UCSC from mRNA sequence data submitted to the international public sequence databases by scientists worldwide. References Benson DA, Cavanaugh M, Clark K, Karsch-Mizrachi I, Lipman DJ, Ostell J, Sayers EW. GenBank. Nucleic Acids Res. 2013 Jan;41(Database issue):D36-42. PMID: 23193287; PMC: PMC3531190 Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL. GenBank: update. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D23-6. PMID: 14681350; PMC: PMC308779 Kent WJ. BLAT - the BLAST-like alignment tool. Genome Res. 2002 Apr;12(4):656-64. PMID: 11932250; PMC: PMC187518 xenoRefGene Other RefSeq Non-Zebrafish RefSeq Genes Genes and Gene Predictions Description This track shows known protein-coding and non-protein-coding genes for organisms other than zebrafish, taken from the NCBI RNA reference sequences collection (RefSeq). The data underlying this track are updated weekly. Display Conventions and Configuration This track follows the display conventions for gene prediction tracks. The color shading indicates the level of review the RefSeq record has undergone: predicted (light), provisional (medium), reviewed (dark). The item labels and display colors of features within this track can be configured through the controls at the top of the track description page. Label: By default, items are labeled by gene name. Click the appropriate Label option to display the accession name instead of the gene name, show both the gene and accession names, or turn off the label completely. Codon coloring: This track contains an optional codon coloring feature that allows users to quickly validate and compare gene predictions. To display codon colors, select the genomic codons option from the Color track by codons pull-down menu. For more information about this feature, go to the Coloring Gene Predictions and Annotations by Codon page. Hide non-coding genes: By default, both the protein-coding and non-protein-coding genes are displayed. If you wish to see only the coding genes, click this box. Methods The RNAs were aligned against the zebrafish genome using blat; those with an alignment of less than 15% were discarded. When a single RNA aligned in multiple places, the alignment having the highest base identity was identified. Only alignments having a base identity level within 0.5% of the best and at least 25% base identity with the genomic sequence were kept. Credits This track was produced at UCSC from RNA sequence data generated by scientists worldwide and curated by the NCBI RefSeq project. References Kent WJ. BLAT--the BLAST-like alignment tool. Genome Res. 2002 Apr;12(4):656-64. PMID: 11932250; PMC: PMC187518 Pruitt KD, Brown GR, Hiatt SM, Thibaud-Nissen F, Astashyn A, Ermolaeva O, Farrell CM, Hart J, Landrum MJ, McGarvey KM et al. RefSeq: an update on mammalian reference sequences. Nucleic Acids Res. 2014 Jan;42(Database issue):D756-63. PMID: 24259432; PMC: PMC3965018 Pruitt KD, Tatusova T, Maglott DR. NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D501-4. PMID: 15608248; PMC: PMC539979 ucscToRefSeq RefSeq Acc RefSeq Accession Mapping and Sequencing Description This track associates UCSC Genome Browser chromosome names to accession identifiers from the NCBI Reference Sequence Database (RefSeq). The data were downloaded from the NCBI assembly database. Credits The data for this track was prepared by Hiram Clawson. simpleRepeat Simple Repeats Simple Tandem Repeats by TRF Variation and Repeats Description This track displays simple tandem repeats (possibly imperfect repeats) located by Tandem Repeats Finder (TRF) which is specialized for this purpose. These repeats can occur within coding regions of genes and may be quite polymorphic. Repeat expansions are sometimes associated with specific diseases. Methods For more information about the TRF program, see Benson (1999). Credits TRF was written by Gary Benson. References Benson G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res. 1999 Jan 15;27(2):573-80. PMID: 9862982; PMC: PMC148217 intronEst Spliced ESTs Zebrafish ESTs That Have Been Spliced mRNA and EST Description This track shows alignments between zebrafish expressed sequence tags (ESTs) in GenBank and the genome that show signs of splicing when aligned against the genome. ESTs are single-read sequences, typically about 500 bases in length, that usually represent fragments of transcribed genes. To be considered spliced, an EST must show evidence of at least one canonical intron (i.e., the genomic sequence between EST alignment blocks must be at least 32 bases in length and have GT/AG ends). By requiring splicing, the level of contamination in the EST databases is drastically reduced at the expense of eliminating many genuine 3' ESTs. For a display of all ESTs (including unspliced), see the zebrafish EST track. Display Conventions and Configuration This track follows the display conventions for PSL alignment tracks. In dense display mode, darker shading indicates a larger number of aligned ESTs. The strand information (+/-) indicates the direction of the match between the EST and the matching genomic sequence. It bears no relationship to the direction of transcription of the RNA with which it might be associated. The description page for this track has a filter that can be used to change the display mode, alter the color, and include/exclude a subset of items within the track. This may be helpful when many items are shown in the track display, especially when only some are relevant to the current task. To use the filter: Type a term in one or more of the text boxes to filter the EST display. For example, to apply the filter to all ESTs expressed in a specific organ, type the name of the organ in the tissue box. To view the list of valid terms for each text box, consult the table in the Table Browser that corresponds to the factor on which you wish to filter. For example, the "tissue" table contains all the types of tissues that can be entered into the tissue text box. Multiple terms may be entered at once, separated by a space. Wildcards may also be used in the filter. If filtering on more than one value, choose the desired combination logic. If "and" is selected, only ESTs that match all filter criteria will be highlighted. If "or" is selected, ESTs that match any one of the filter criteria will be highlighted. Choose the color or display characteristic that should be used to highlight or include/exclude the filtered items. If "exclude" is chosen, the browser will not display ESTs that match the filter criteria. If "include" is selected, the browser will display only those ESTs that match the filter criteria. This track may also be configured to display base labeling, a feature that allows the user to display all bases in the aligning sequence or only those that differ from the genomic sequence. For more information about this option, go to the Base Coloring for Alignment Tracks page. Several types of alignment gap may also be colored; for more information, go to the Alignment Insertion/Deletion Display Options page. Methods To make an EST, RNA is isolated from cells and reverse transcribed into cDNA. Typically, the cDNA is cloned into a plasmid vector and a read is taken from the 5' and/or 3' primer. For most — but not all — ESTs, the reverse transcription is primed by an oligo-dT, which hybridizes with the poly-A tail of mature mRNA. The reverse transcriptase may or may not make it to the 5' end of the mRNA, which may or may not be degraded. In general, the 3' ESTs mark the end of transcription reasonably well, but the 5' ESTs may end at any point within the transcript. Some of the newer cap-selected libraries cover transcription start reasonably well. Before the cap-selection techniques emerged, some projects used random rather than poly-A priming in an attempt to retrieve sequence distant from the 3' end. These projects were successful at this, but as a side effect also deposited sequences from unprocessed mRNA and perhaps even genomic sequences into the EST databases. Even outside of the random-primed projects, there is a degree of non-mRNA contamination. Because of this, a single unspliced EST should be viewed with considerable skepticism. To generate this track, zebrafish ESTs from GenBank were aligned against the genome using blat. Note that the maximum intron length allowed by blat is 750,000 bases, which may eliminate some ESTs with very long introns that might otherwise align. When a single EST aligned in multiple places, the alignment having the highest base identity was identified. Only alignments having a base identity level within 0.5% of the best and at least 96% base identity with the genomic sequence are displayed in this track. Credits This track was produced at UCSC from EST sequence data submitted to the international public sequence databases by scientists worldwide. References Benson DA, Cavanaugh M, Clark K, Karsch-Mizrachi I, Lipman DJ, Ostell J, Sayers EW. GenBank. Nucleic Acids Res. 2013 Jan;41(Database issue):D36-42. PMID: 23193287; PMC: PMC3531190 Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL. GenBank: update. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D23-6. PMID: 14681350; PMC: PMC308779 Kent WJ. BLAT - the BLAST-like alignment tool. Genome Res. 2002 Apr;12(4):656-64. PMID: 11932250; PMC: PMC187518 tRNAs tRNA Genes Transfer RNA Genes Identified with tRNAscan-SE Genes and Gene Predictions Description This track displays tRNA genes predicted by using tRNAscan-SE v.1.23. tRNAscan-SE is an integrated program that uses tRNAscan (Fichant) and an A/B box motif detection algorithm (Pavesi) as pre-filters to obtain an initial list of tRNA candidates. The program then filters these candidates with a covariance model-based search program COVE (Eddy) to obtain a highly specific set of primary sequence and secondary structure predictions that represent 99-100% of true tRNAs with a false positive rate of fewer than 1 per 15 gigabases. Detailed tRNA annotations for eukaryotes, bacteria, and archaea are available at Genomic tRNA Database (GtRNAdb). What does the tRNAscan-SE score mean? Anything with a score above 20 bits is likely to be derived from a tRNA, although this does not indicate whether the tRNA gene still encodes a functional tRNA molecule (i.e. tRNA-derived SINES probably do not function in the ribosome in translation). Vertebrate tRNAs with scores of >60.0 (bits) are likely to encode functional tRNA genes, and those with scores below ~45 have sequence or structural features that indicate they probably are no longer involved in translation. tRNAs with scores between 45-60 bits are in the "grey" zone, and may or may not have all the required features to be functional. In these cases, tRNAs should be inspected carefully for loss of specific primary or secondary structure features (usually in alignments with other genes of the same isotype), in order to make a better educated guess. These rough score range guides are not exact, nor are they based on specific biochemical studies of atypical tRNA features, so please treat them accordingly. Please note that tRNA genes marked as "Pseudo" are low scoring predictions that are mostly pseudogenes or tRNA-derived elements. These genes do not usually fold into a typical cloverleaf tRNA secondary structure and the provided images of the predicted secondary structures may appear rotated. Credits Both tRNAscan-SE and GtRNAdb are maintained by the Lowe Lab at UCSC. Cove-predicted tRNA secondary structures were rendered by NAVIEW (c) 1988 Robert E. Bruccoleri. References When making use of these data, please cite the following articles: Chan PP, Lowe TM. GtRNAdb: a database of transfer RNA genes detected in genomic sequence. Nucleic Acids Res. 2009 Jan;37(Database issue):D93-7. PMID: 18984615; PMC: PMC2686519 Eddy SR, Durbin R. RNA sequence analysis using covariance models. Nucleic Acids Res. 1994 Jun 11;22(11):2079-88. PMID: 8029015; PMC: PMC308124 Fichant GA, Burks C. Identifying potential tRNA genes in genomic DNA sequences. J Mol Biol. 1991 Aug 5;220(3):659-71. PMID: 1870126 Lowe TM, Eddy SR. tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res. 1997 Mar 1;25(5):955-64. PMID: 9023104; PMC: PMC146525 Pavesi A, Conterio F, Bolchi A, Dieci G, Ottonello S. Identification of new eukaryotic tRNA genes in genomic DNA databases by a multistep weight matrix analysis of transcriptional control regions. Nucleic Acids Res. 1994 Apr 11;22(7):1247-56. PMID: 8165140; PMC: PMC523650 UMassChIP-SeqComposite UMass ChIP-Seq U Mass ChIP-Seq Expression and Regulation Description and Methods H3K4me1 and H3K4me3 binding at 24 hours post fertilization in the zebrafish embryo. Methylation of lysine 4 on histone H3 can serve as a landmark of cis regulatory elements in the genome. In particular, tri-methylation of lysine 4 (H3K4me3) usually marks promoters of active genes, while mono-methylation (H3K4me1) can be more widely distributed and associates with multiple regulatory elements, including enhancers and insulators. Given the increasing importance and value of the zebrafish as a model system, an initial assay of H3K4me1 and H3K4me3 binding in the zebrafish embryo at 24 hours post fertilization was undertaken, a time at which most of the organs systems have begun to develop. These data provide a valuable resource for preliminary identification of cis regulatory features in the zebrafish embryonic genome. Display Conventions and Configuration Signal - Density coverage of sequence tags for a given sample. Peaks - Genome coordinates of highest tag density within a hotspot; identified using MACS. Hotspots - Regions of enrichment for binding over input alone (p<1x10-5); identified using MACS. Methods For each ChIP, 200 wild-type zebrafish embryos staged at 24 hours post fertilization (hpf) were dissociated into single cell suspensions. Cells were cross-linked with a 1% formaldehyde/PBS solution for 10 minutes at room temperature. After adding glycine, the samples were centrifuged and pellets resuspended in lysis buffer. The samples were sonicated using a Microsonicator (Cole and Palmer Instruments) to a size distribution between 200-1,000 bp. Immunoprecipitation was performed using anti-H3K4me1 (ab8895, Abcam) or anti-H3K4me3 antibody (ab8580, Abcam) overnight at 4°C. Both antibody-treated and untreated samples were incubated with protein A agarose beads for one hour at 4°C and subsequently washed. Immunoprecipitated DNAs were purified using a PCR purification kit. DNA, from both antibody and input samples, was polished and A-tailed followed by ligation to Illumina adapters. Adaptor-ligated fragments were gel-purified and amplified by PCR, followed by a final gel purification. Single end 36 or 72 bp reads from adaptor-ligated libraries were obtained by deep sequencing on Illumina Genome Analyzers operated by the UMass Center for AIDS Research Deep Sequencing Core. Sequence tags were mapped to the zebrafish genome (Zv7) using Bowtie, and only tags with unique genomic coordinates and less than 2 bp of mismatch were included in subsequent analyses. The "Signal" track was generated by extending each uniquely mapped sequence tag to 250 bp in length, followed by coverage calculation for each position in a 250 bp moving window. To minimize file size of these annotation tracks, only genomic positions with at least 10 sequence tags were used to generate wiggle files. Regions of H3K4me1 or H3K4me3 enrichment over input (referred to hereafter as "hotspots") and "peaks" of binding within these enriched regions were determined using the Model-based Analysis of ChIP-Seq algorithm (MACS, version 1.4; (Zhang, et al. 2008) with the default settings and the following modified parameters: -f BED -w --single-wig --gsize 1700000000 --tsize 36 --bw 150). Verification Several of the identified peaks have been functionally validated using in vivo reporter assays in zebrafish. Credits These data were generated by the Lawson Lab. Aaron Aday generated the ChIP-Seq libraries. Computational analysis was performed by Abirami Lakshmanan and Dr. Julie Zhu. Contact: Nathan Lawson (Nathan.lawson@um-null-assmed.edu) References Aday AW, Zhu LJ, Lakshmanan A, Wang J, Lawson ND. Identification of cis regulatory features in the embryonic zebrafish genome through large-scale profiling of H3K4me1 and H3K4me3 binding sites. Dev Biol. 2011 Sep 15;357(2):450-62. PMID: 21435340; PMC: PMC3273848 Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, Nusbaum C, Myers RM, Brown M, Li W et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008;9(9):R137. PMID: 18798982; PMC: PMC2592715 UMassME3Hotspot UMassME3Hotspot U Mass ChIP-Seq H3K4me3 Binding Hot Spots at 24 hours Post Fertilization Expression and Regulation UMassME3Peak UMassME3Peak U Mass ChIP-Seq H3K4me3 Binding Peaks at 24 hours Post Fertilization Expression and Regulation UMassME3 UMassME3 U Mass ChIP-Seq H3K4me3 Binding at 24 hours Post Fertilization Expression and Regulation UMassME1Hotspot UMassME1Hotspot U Mass ChIP-Seq H3K4me1 Binding Hot Spots at 24 hours Post Fertilization Expression and Regulation UMassME1Peak UMassME1Peak U Mass ChIP-Seq H3K4me1 Binding Peaks at 24 hours Post Fertilization Expression and Regulation UMassME1 UMassME1 U Mass ChIP-Seq H3K4me1 Binding at 24 hours Post Fertilization Expression and Regulation UMassInput UMass ChIP-Seq U Mass ChIP-Seq Input Signal at 24 hours Post Fertilization Expression and Regulation uniprot UniProt UniProt SwissProt/TrEMBL Protein Annotations Genes and Gene Predictions Description This track shows protein sequences and annotations on them from the UniProt/SwissProt database, mapped to genomic coordinates. UniProt/SwissProt data has been curated from scientific publications by the UniProt staff, UniProt/TrEMBL data has been predicted by various computational algorithms. The annotations are divided into multiple subtracks, based on their "feature type" in UniProt. The first two subtracks below - one for SwissProt, one for TrEMBL - show the alignments of protein sequences to the genome, all other tracks below are the protein annotations mapped through these alignments to the genome. Track Name Description UCSC Alignment, SwissProt = curated protein sequences Protein sequences from SwissProt mapped to the genome. All other tracks are (start,end) SwissProt annotations on these sequences mapped through this alignment. Even protein sequences without a single curated annotation (splice isoforms) are visible in this track. Each UniProt protein has one main isoform, which is colored in dark. Alternative isoforms are sequences that do not have annotations on them and are colored in light-blue. They can be hidden with the TrEMBL/Isoform filter (see below). UCSC Alignment, TrEMBL = predicted protein sequences Protein sequences from TrEMBL mapped to the genome. All other tracks below are (start,end) TrEMBL annotations mapped to the genome using this track. This track is hidden by default. To show it, click its checkbox on the track configuration page. UniProt Signal Peptides Regions found in proteins destined to be secreted, generally cleaved from mature protein. UniProt Extracellular Domains Protein domains with the comment "Extracellular". UniProt Transmembrane Domains Protein domains of the type "Transmembrane". UniProt Cytoplasmic Domains Protein domains with the comment "Cytoplasmic". UniProt Polypeptide Chains Polypeptide chain in mature protein after post-processing. UniProt Regions of Interest Regions that have been experimentally defined, such as the role of a region in mediating protein-protein interactions or some other biological process. UniProt Domains Protein domains, zinc finger regions and topological domains. UniProt Disulfide Bonds Disulfide bonds. UniProt Amino Acid Modifications Glycosylation sites, modified residues and lipid moiety-binding regions. UniProt Amino Acid Mutations Mutagenesis sites and sequence variants. UniProt Protein Primary/Secondary Structure Annotations Beta strands, helices, coiled-coil regions and turns. UniProt Sequence Conflicts Differences between Genbank sequences and the UniProt sequence. UniProt Repeats Regions of repeated sequence motifs or repeated domains. UniProt Other Annotations All other annotations, e.g. compositional bias For consistency and convenience for users of mutation-related tracks, the subtrack "UniProt/SwissProt Variants" is a copy of the track "UniProt Variants" in the track group "Phenotype and Literature", or "Variation and Repeats", depending on the assembly. Display Conventions and Configuration Genomic locations of UniProt/SwissProt annotations are labeled with a short name for the type of annotation (e.g. "glyco", "disulf bond", "Signal peptide" etc.). A click on them shows the full annotation and provides a link to the UniProt/SwissProt record for more details. TrEMBL annotations are always shown in light blue, except in the Signal Peptides, Extracellular Domains, Transmembrane Domains, and Cytoplamsic domains subtracks. Mouse over a feature to see the full UniProt annotation comment. For variants, the mouse over will show the full name of the UniProt disease acronym. The subtracks for domains related to subcellular location are sorted from outside to inside of the cell: Signal peptide, extracellular, transmembrane, and cytoplasmic. In the "UniProt Modifications" track, lipoification sites are highlighted in dark blue, glycosylation sites in dark green, and phosphorylation in light green. Duplicate annotations are removed as far as possible: if a TrEMBL annotation has the same genome position and same feature type, comment, disease and mutated amino acids as a SwissProt annotation, it is not shown again. Two annotations mapped through different protein sequence alignments but with the same genome coordinates are only shown once. On the configuration page of this track, you can choose to hide any TrEMBL annotations. This filter will also hide the UniProt alternative isoform protein sequences because both types of information are less relevant to most users. Please contact us if you want more detailed filtering features. Note that for the human hg38 assembly and SwissProt annotations, there also is a public track hub prepared by UniProt itself, with genome annotations maintained by UniProt using their own mapping method based on those Gencode/Ensembl gene models that are annotated in UniProt for a given protein. For proteins that differ from the genome, UniProt's mapping method will, in most cases, map a protein and its annotations to an unexpected location (see below for details on UCSC's mapping method). Methods Briefly, UniProt protein sequences were aligned to the transcripts associated with the protein, the top-scoring alignments were retained, and the result was projected to the genome through a transcript-to-genome alignment. Depending on the genome, the transcript-genome alignments was either provided by the source database (NBCI RefSeq), created at UCSC (UCSC RefSeq) or derived from the transcripts (Ensembl/Augustus). The transcript set is NCBI RefSeq for hg38, UCSC RefSeq for hg19 (due to alt/fix haplotype misplacements in the NCBI RefSeq set on hg19). For other genomes, RefSeq, Ensembl and Augustus are tried, in this order. The resulting protein-genome alignments of this process are available in the file formats for liftOver or pslMap from our data archive (see "Data Access" section below). An important step of the mapping process protein -> transcript -> genome is filtering the alignment from protein to transcript. Due to differences between the UniProt proteins and the transcripts (proteins were made many years before the transcripts were made, and human genomes have variants), the transcript with the highest BLAST score when aligning the protein to all transcripts is not always the correct transcript for a protein sequence. Therefore, the protein sequence is aligned to only a very short list of one or sometimes more transcripts, selected by a three-step procedure: Use transcripts directly annotated by UniProt: for organisms that have a RefSeq transcript track, proteins are aligned to the RefSeq transcripts that are annotated by UniProt for this particular protein. Use transcripts for NCBI Gene ID annotated by UniProt: If no transcripts are annotated on the protein, or the annotated ones have been deprecated by NCBI, but a NCBI Gene ID is annotated, the RefSeq transcripts for this Gene ID are used. This can result in multiple matching transcripts for a protein. Use best matching transcript: If no NCBI Gene is annotated, then BLAST scores are used to pick the transcripts. There can be multiple transcripts for one protein, as their coding sequences can be identical. All transcripts within 1% of the highest observed BLAST score are used. For strategy 2 and 3, many of the transcripts found do not differ in coding sequence, so the resulting alignments on the genome will be identical. Therefore, any identical alignments are removed in a final filtering step. The details page of these alignments will contain a list of all transcripts that result in the same protein-genome alignment. On hg38, only a handful of edge cases (pseudogenes, very recently added proteins) remain in 2023 where strategy 3 has to be used. In other words, when an NCBI or UCSC RefSeq track is used for the mapping and to align a protein sequence to the correct transcript, we use a three stage process: If UniProt has annotated a given RefSeq transcript for a given protein sequence, the protein is aligned to this transcript. Any difference in the version suffix is tolerated in this comparison. If no transcript is annotated or the transcript cannot be found in the NCBI/UCSC RefSeq track, the UniProt-annotated NCBI Gene ID is resolved to a set of NCBI RefSeq transcript IDs via the most current version of NCBI genes tables. Only the top match of the resulting alignments and all others within 1% of its score are used for the mapping. If no transcript can be found after step (2), the protein is aligned to all transcripts, the top match, and all others within 1% of its score are used. This system was designed to resolve the problem of incorrect mappings of proteins, mostly on hg38, due to differences between the SwissProt sequences and the genome reference sequence, which has changed since the proteins were defined. The problem is most pronounced for gene families composed of either very repetitive or very similar proteins. To make sure that the alignments always go to the best chromosome location, all _alt and _fix reference patch sequences are ignored for the alignment, so the patches are entirely free of UniProt annotations. Please contact us if you have feedback on this process or example edge cases. We are not aware of a way to evaluate the results completely and in an automated manner. Proteins were aligned to transcripts with TBLASTN, converted to PSL, filtered with pslReps (93% query coverage, keep alignments within top 1% score), lifted to genome positions with pslMap and filtered again with pslReps. UniProt annotations were obtained from the UniProt XML file. The UniProt annotations were then mapped to the genome through the alignment described above using the pslMap program. This approach draws heavily on the LS-SNP pipeline by Mark Diekhans. Like all Genome Browser source code, the main script used to build this track can be found on Github. Older releases This track is automatically updated on an ongoing basis, every 2-3 months. The current version name is always shown on the track details page, it includes the release of UniProt, the version of the transcript set and a unique MD5 that is based on the protein sequences, the transcript sequences, the mapping file between both and the transcript-genome alignment. The exact transcript that was used for the alignment is shown when clicking a protein alignment in one of the two alignment tracks. For reproducibility of older analysis results and for manual inspection, previous versions of this track are available for browsing in the form of the UCSC UniProt Archive Track Hub (click this link to connect the hub now). The underlying data of all releases of this track (past and current) can be obtained from our downloads server, including the UniProt protein-to-genome alignment. Data Access The raw data of the current track can be explored interactively with the Table Browser, or the Data Integrator. For automated analysis, the genome annotation is stored in a bigBed file that can be downloaded from the download server. The exact filenames can be found in the track configuration file. Annotations can be converted to ASCII text by our tool bigBedToBed which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain only features within a given range, for example: bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/danRer7/uniprot/unipStruct.bb -chrom=chr6 -start=0 -end=1000000 stdout Please refer to our mailing list archives for questions, or our Data Access FAQ for more information. Lifting from UniProt to genome coordinates in pipelines To facilitate mapping protein coordinates to the genome, we provide the alignment files in formats that are suitable for our command line tools. Our command line programs liftOver or pslMap can be used to map coordinates on protein sequences to genome coordinates. The filenames are unipToGenome.over.chain.gz (liftOver) and unipToGenomeLift.psl.gz (pslMap). Example commands: wget -q https://hgdownload.soe.ucsc.edu/goldenPath/archive/hg38/uniprot/2022_03/unipToGenome.over.chain.gz wget -q https://hgdownload.soe.ucsc.edu/admin/exe/linux.x86_64/liftOver chmod a+x liftOver echo 'Q99697 1 10 annotationOnProtein' > prot.bed liftOver prot.bed unipToGenome.over.chain.gz genome.bed cat genome.bed Credits This track was created by Maximilian Haeussler at UCSC, with a lot of input from Chris Lee, Mark Diekhans and Brian Raney, feedback from the UniProt staff, Alejo Mujica, Regeneron Pharmaceuticals and Pia Riestra, GeneDx. Thanks to UniProt for making all data available for download. References UniProt Consortium. Reorganizing the protein space at the Universal Protein Resource (UniProt). Nucleic Acids Res. 2012 Jan;40(Database issue):D71-5. PMID: 22102590; PMC: PMC3245120 Yip YL, Scheib H, Diemand AV, Gattiker A, Famiglietti LM, Gasteiger E, Bairoch A. The Swiss-Prot variant page and the ModSNP database: a resource for sequence and structure information on human protein variants. Hum Mutat. 2004 May;23(5):464-70. PMID: 15108278 unipConflict Seq. Conflicts UniProt Sequence Conflicts Genes and Gene Predictions unipRepeat Repeats UniProt Repeats Genes and Gene Predictions unipStruct Structure UniProt Protein Primary/Secondary Structure Annotations Genes and Gene Predictions unipOther Other Annot. UniProt Other Annotations Genes and Gene Predictions unipMut Mutations UniProt Amino Acid Mutations Genes and Gene Predictions unipModif AA Modifications UniProt Amino Acid Modifications Genes and Gene Predictions unipDomain Domains UniProt Domains Genes and Gene Predictions unipDisulfBond Disulf. Bonds UniProt Disulfide Bonds Genes and Gene Predictions unipChain Chains UniProt Mature Protein Products (Polypeptide Chains) Genes and Gene Predictions unipLocCytopl Cytoplasmic UniProt Cytoplasmic Domains Genes and Gene Predictions unipLocTransMemb Transmembrane UniProt Transmembrane Domains Genes and Gene Predictions unipInterest Interest UniProt Regions of Interest Genes and Gene Predictions unipLocExtra Extracellular UniProt Extracellular Domain Genes and Gene Predictions unipLocSignal Signal Peptide UniProt Signal Peptides Genes and Gene Predictions unipAliTrembl TrEMBL Aln. UCSC alignment of TrEMBL proteins to genome Genes and Gene Predictions unipAliSwissprot SwissProt Aln. UCSC alignment of SwissProt proteins to genome (dark blue: main isoform, light blue: alternative isoforms) Genes and Gene Predictions pubsBingBlat Web Sequences DNA Sequences in Web Pages Indexed by Bing.com / Microsoft Research Literature Description This track is powered by Bing! and Microsoft Research. UCSC collaborators at Microsoft Research (Bob Davidson, David Heckerman) implemented a DNA sequence detector and processed thirty days of web crawler updates, which covers roughly 40 billion webpages. The results were mapped with BLAT to the genome. Display Convention and Configuration The track indicates the location of sequences on web pages mapped to the genome, labelled with the web page URL. If the web page includes invisible meta data, then the first author and a year of publication is shown instead of the URL. All matches of one web page are grouped ("chained") together. Web page titles are shown when you move the mouse cursor over the features. Thicker parts of the features (exons) represent matching sequences, connected by thin lines to matches from the same web page within 30 kbp. The subtrack "individual sequence matches" activates automatically when the user clicks a sequence match and follows the link "Show sequence matches individually" from the details page. Mouse-overs show flanking text around the sequence, and clicking features links to BLAT alignments. - --> Methods All file types (PDFs and various Microsoft Office formats) were converted to text. The results were processed to find groups of words that look like DNA/RNA sequences. These were then mapped with BLAT to the human genome using the same software as used in the Publication track. Credits DNA sequence detection by Bob Davidson at Microsoft Research. HTML parsing and sequence mapping by Maximilian Haeussler at UCSC. References Aerts S, Haeussler M, van Vooren S, Griffith OL, Hulpiau P, Jones SJ, Montgomery SB, Bergman CM, Open Regulatory Annotation Consortium. Text-mining assisted regulatory annotation. Genome Biol. 2008;9(2):R31. PMID: 18271954; PMC: PMC2374703 Haeussler M, Gerner M, Bergman CM. Annotating genes and genomes with DNA sequences extracted from biomedical articles. Bioinformatics. 2011 Apr 1;27(7):980-6. PMID: 21325301; PMC: PMC3065681 Van Noorden R. Trouble at the text mine. Nature. 2012 Mar 7;483(7388):134-5. est Zebrafish ESTs Zebrafish ESTs Including Unspliced mRNA and EST Description This track shows alignments between zebrafish expressed sequence tags (ESTs) in GenBank and the genome. ESTs are single-read sequences, typically about 500 bases in length, that usually represent fragments of transcribed genes. Display Conventions and Configuration This track follows the display conventions for PSL alignment tracks. In dense display mode, the items that are more darkly shaded indicate matches of better quality. The strand information (+/-) indicates the direction of the match between the EST and the matching genomic sequence. It bears no relationship to the direction of transcription of the RNA with which it might be associated. The description page for this track has a filter that can be used to change the display mode, alter the color, and include/exclude a subset of items within the track. This may be helpful when many items are shown in the track display, especially when only some are relevant to the current task. To use the filter: Type a term in one or more of the text boxes to filter the EST display. For example, to apply the filter to all ESTs expressed in a specific organ, type the name of the organ in the tissue box. To view the list of valid terms for each text box, consult the table in the Table Browser that corresponds to the factor on which you wish to filter. For example, the "tissue" table contains all the types of tissues that can be entered into the tissue text box. Multiple terms may be entered at once, separated by a space. Wildcards may also be used in the filter. If filtering on more than one value, choose the desired combination logic. If "and" is selected, only ESTs that match all filter criteria will be highlighted. If "or" is selected, ESTs that match any one of the filter criteria will be highlighted. Choose the color or display characteristic that should be used to highlight or include/exclude the filtered items. If "exclude" is chosen, the browser will not display ESTs that match the filter criteria. If "include" is selected, the browser will display only those ESTs that match the filter criteria. This track may also be configured to display base labeling, a feature that allows the user to display all bases in the aligning sequence or only those that differ from the genomic sequence. For more information about this option, go to the Base Coloring for Alignment Tracks page. Several types of alignment gap may also be colored; for more information, go to the Alignment Insertion/Deletion Display Options page. Methods To make an EST, RNA is isolated from cells and reverse transcribed into cDNA. Typically, the cDNA is cloned into a plasmid vector and a read is taken from the 5' and/or 3' primer. For most — but not all — ESTs, the reverse transcription is primed by an oligo-dT, which hybridizes with the poly-A tail of mature mRNA. The reverse transcriptase may or may not make it to the 5' end of the mRNA, which may or may not be degraded. In general, the 3' ESTs mark the end of transcription reasonably well, but the 5' ESTs may end at any point within the transcript. Some of the newer cap-selected libraries cover transcription start reasonably well. Before the cap-selection techniques emerged, some projects used random rather than poly-A priming in an attempt to retrieve sequence distant from the 3' end. These projects were successful at this, but as a side effect also deposited sequences from unprocessed mRNA and perhaps even genomic sequences into the EST databases. Even outside of the random-primed projects, there is a degree of non-mRNA contamination. Because of this, a single unspliced EST should be viewed with considerable skepticism. To generate this track, zebrafish ESTs from GenBank were aligned against the genome using blat. Note that the maximum intron length allowed by blat is 750,000 bases, which may eliminate some ESTs with very long introns that might otherwise align. When a single EST aligned in multiple places, the alignment having the highest base identity was identified. Only alignments having a base identity level within 0.5% of the best and at least 96% base identity with the genomic sequence were kept. Credits This track was produced at UCSC from EST sequence data submitted to the international public sequence databases by scientists worldwide. References Benson DA, Cavanaugh M, Clark K, Karsch-Mizrachi I, Lipman DJ, Ostell J, Sayers EW. GenBank. Nucleic Acids Res. 2013 Jan;41(Database issue):D36-42. PMID: 23193287; PMC: PMC3531190 Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL. GenBank: update. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D23-6. PMID: 14681350; PMC: PMC308779 Kent WJ. BLAT - the BLAST-like alignment tool. Genome Res. 2002 Apr;12(4):656-64. PMID: 11932250; PMC: PMC187518 mrna Zebrafish mRNAs Zebrafish mRNAs from GenBank mRNA and EST Description The mRNA track shows alignments between zebrafish mRNAs in GenBank and the genome. Display Conventions and Configuration This track follows the display conventions for PSL alignment tracks. In dense display mode, the items that are more darkly shaded indicate matches of better quality. The description page for this track has a filter that can be used to change the display mode, alter the color, and include/exclude a subset of items within the track. This may be helpful when many items are shown in the track display, especially when only some are relevant to the current task. To use the filter: Type a term in one or more of the text boxes to filter the mRNA display. For example, to apply the filter to all mRNAs expressed in a specific organ, type the name of the organ in the tissue box. To view the list of valid terms for each text box, consult the table in the Table Browser that corresponds to the factor on which you wish to filter. For example, the "tissue" table contains all the types of tissues that can be entered into the tissue text box. Multiple terms may be entered at once, separated by a space. Wildcards may also be used in the filter. If filtering on more than one value, choose the desired combination logic. If "and" is selected, only mRNAs that match all filter criteria will be highlighted. If "or" is selected, mRNAs that match any one of the filter criteria will be highlighted. Choose the color or display characteristic that should be used to highlight or include/exclude the filtered items. If "exclude" is chosen, the browser will not display mRNAs that match the filter criteria. If "include" is selected, the browser will display only those mRNAs that match the filter criteria. This track may also be configured to display codon coloring, a feature that allows the user to quickly compare mRNAs against the genomic sequence. For more information about this option, go to the Codon and Base Coloring for Alignment Tracks page. Several types of alignment gap may also be colored; for more information, go to the Alignment Insertion/Deletion Display Options page. Methods GenBank zebrafish mRNAs were aligned against the genome using the blat program. When a single mRNA aligned in multiple places, the alignment having the highest base identity was found. Only alignments having a base identity level within 0.5% of the best and at least 96% base identity with the genomic sequence were kept. Credits The mRNA track was produced at UCSC from mRNA sequence data submitted to the international public sequence databases by scientists worldwide. References Benson DA, Cavanaugh M, Clark K, Karsch-Mizrachi I, Lipman DJ, Ostell J, Sayers EW. GenBank. Nucleic Acids Res. 2013 Jan;41(Database issue):D36-42. PMID: 23193287; PMC: PMC3531190 Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL. GenBank: update. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D23-6. PMID: 14681350; PMC: PMC308779 Kent WJ. BLAT - the BLAST-like alignment tool. Genome Res. 2002 Apr;12(4):656-64. PMID: 11932250; PMC: PMC187518 mgcFullMrna ZGC Genes Zebrafish Gene Collection Full ORF mRNAs Genes and Gene Predictions Description This track shows alignments of zebrafish mRNAs from the Zebrafish Gene Collection (ZGC) having full-length open reading frames (ORFs) to the genome. This is a subproject of the Mammalian Gene Collection (MGC) project. The goal of the Mammalian Gene Collection is to provide researchers with unrestricted access to sequence-validated full-length protein-coding cDNA clones for human, mouse, and rat genes. Display Conventions and Configuration The track follows the display conventions for gene prediction tracks. An optional codon coloring feature is available for quick validation and comparison of gene predictions. To display codon colors, select the genomic codons option from the Color track by codons pull-down menu. For more information about this feature, go to the Coloring Gene Predictions and Annotations by Codon page. Methods GenBank zebrafish ZGC mRNAs identified as having full-length ORFs were aligned against the genome using blat. When a single mRNA aligned in multiple places, the alignment having the highest base identity was found. Only alignments having a base identity level within 1% of the best and at least 95% base identity with the genomic sequence were kept. Credits The zebrafish ZGC full-length mRNA track was produced at UCSC from mRNA sequence data submitted to GenBank by the Zebrafish Gene Collection project. References Mammalian Gene Collection project references. Kent WJ. BLAT - the BLAST-like alignment tool. Genome Res. 2002 Apr;12(4):656-64. PMID: 11932250; PMC: PMC187518 cons8way Conservation Multiz Alignment & Conservation (8 Species) Comparative Genomics Description This track shows multiple alignments of 8 vertebrate species and measurements of evolutionary conservation using two methods (phastCons and phyloP) from the PHAST package, for all species (vertebrate) and a subset of fish species. The multiple alignments were generated using multiz and other tools in the UCSC/Penn State Bioinformatics comparative genomics alignment pipeline. Conserved elements identified by phastCons are also displayed in this track. PhastCons (which has been used in previous Conservation tracks) is a hidden Markov model-based method that estimates the probability that each nucleotide belongs to a conserved element, based on the multiple alignment. It considers not just each individual alignment column, but also its flanking columns. By contrast, phyloP separately measures conservation at individual columns, ignoring the effects of their neighbors. As a consequence, the phyloP plots have a less smooth appearance than the phastCons plots, with more "texture" at individual sites. The two methods have different strengths and weaknesses. PhastCons is sensitive to "runs" of conserved sites, and is therefore effective for picking out conserved elements. PhyloP, on the other hand, is more appropriate for evaluating signatures of selection at particular nucleotides or classes of nucleotides (e.g., third codon positions, or first positions of miRNA target sites). Another important difference is that phyloP can measure acceleration (faster evolution than expected under neutral drift) as well as conservation (slower than expected evolution). In the phyloP plots, sites predicted to be conserved are assigned positive scores (and shown in blue), while sites predicted to be fast-evolving are assigned negative scores (and shown in red). The absolute values of the scores represent -log p-values under a null hypothesis of neutral evolution. The phastCons scores, by contrast, represent probabilities of negative selection and range between 0 and 1. Both phastCons and phyloP treat alignment gaps and unaligned nucleotides as missing data, and both were run with the same parameters for each species set (vertebrates and fish). Thus, in regions in which only fish appear in the alignment, both sets of scores will be the same, but in regions in which additional species are available, the vertebrate scores may differ from the fish scores. The alternative plots help to identify sequences that are under different evolutionary pressures in, say, fish and non-fish. The species aligned for this track include the mammal, amphibian, and fish clades. Compared to the previous 6-vertebrate alignment (danRer6), this track includes 2 additional species (fugu, medaka). (Table 1). Missing sequence in the assemblies is highlighted in the track display by regions of yellow when zoomed out and Ns displayed at base level (see Gap Annotation, below). OrganismSpeciesRelease dateUCSC versionalignment type ZebrafishDanio rerio Jul. 2010danRer7reference species MedakaOryzias latipes Oct. 2005oryLat2MAF Net SticklebackGasterosteus aculeatus Feb. 2006gasAcu1MAF Net TetraodonTetraodon nigroviridis Mar. 2007tetNig2MAF Net FuguTakifugu rubripes Oct. 2004fr2MAF Net X. tropicalisXenopus tropicalis Aug. 2005xenTro2MAF Net MouseMus musculus July 2007mm9MAF Net HumanHomo sapiens Feb. 2009 hg19/GRCh37MAF Net Table 1. Genome assemblies included in the 8-way Conservation track. Downloads for data in this track are available: Multiz alignments (MAF format), and phylogenetic trees PhyloP conservation (WIG format) PhastCons conservation (WIG format) Display Conventions and Configuration The track configuration options allow the user to display either the vertebrate or fish conservation scores, or both simultaneously. In full and pack display modes, conservation scores are displayed as a wiggle track (histogram) in which the height reflects the size of the score. The conservation wiggles can be configured in a variety of ways to highlight different aspects of the displayed information. Click the Graph configuration help link for an explanation of the configuration options. Pairwise alignments of each species to the zebrafish genome are displayed below the conservation histogram as a grayscale density plot (in pack mode) or as a wiggle (in full mode) that indicates alignment quality. In dense display mode, conservation is shown in grayscale using darker values to indicate higher levels of overall conservation as scored by phastCons. Checkboxes on the track configuration page allow selection of the species to include in the pairwise display. Configuration buttons are available to select all of the species (Set all), deselect all of the species (Clear all), or use the default settings (Set defaults). By default, the all 8 species are included in the pairwise display: zebrafish, medaka, stickleback, tetraodon, fugu, x. tropicalis (frog), mouse, human. Note that excluding species from the pairwise display does not alter the the conservation score display. To view detailed information about the alignments at a specific position, zoom the display in to 30,000 or fewer bases, then click on the alignment. Gap Annotation The Display chains between alignments configuration option enables display of gaps between alignment blocks in the pairwise alignments in a manner similar to the Chain track display. The following conventions are used: Single line: No bases in the aligned species. Possibly due to a lineage-specific insertion between the aligned blocks in the zebrafish genome or a lineage-specific deletion between the aligned blocks in the aligning species. Double line: Aligning species has one or more unalignable bases in the gap region. Possibly due to excessive evolutionary distance between species or independent indels in the region between the aligned blocks in both species. Pale yellow coloring: Aligning species has Ns in the gap region. Reflects uncertainty in the relationship between the DNA of both species, due to lack of sequence in relevant portions of the aligning species. Genomic Breaks Discontinuities in the genomic context (chromosome, scaffold or region) of the aligned DNA in the aligning species are shown as follows: Vertical blue bar: Represents a discontinuity that persists indefinitely on either side, e.g. a large region of DNA on either side of the bar comes from a different chromosome in the aligned species due to a large scale rearrangement. Green square brackets: Enclose shorter alignments consisting of DNA from one genomic context in the aligned species nested inside a larger chain of alignments from a different genomic context. The alignment within the brackets may represent a short misalignment, a lineage-specific insertion of a transposon in the zebrafish genome that aligns to a paralogous copy somewhere else in the aligned species, or other similar occurrence. Base Level When zoomed-in to the base-level display, the track shows the base composition of each alignment. The numbers and symbols on the Gaps line indicate the lengths of gaps in the zebrafish sequence at those alignment positions relative to the longest non-zebrafish sequence. If there is sufficient space in the display, the size of the gap is shown. If the space is insufficient and the gap size is a multiple of 3, a "*" is displayed; other gap sizes are indicated by "+". Codon translation is available in base-level display mode if the displayed region is identified as a coding segment. To display this annotation, select the species for translation from the pull-down menu in the Codon Translation configuration section at the top of the page. Then, select one of the following modes: No codon translation: The gene annotation is not used; the bases are displayed without translation. Use default species reading frames for translation: The annotations from the genome displayed in the Default species to establish reading frame pull-down menu are used to translate all the aligned species present in the alignment. Use reading frames for species if available, otherwise no translation: Codon translation is performed only for those species where the region is annotated as protein coding. Use reading frames for species if available, otherwise use default species: Codon translation is done on those species that are annotated as being protein coding over the aligned region using species-specific annotation; the remaining species are translated using the default species annotation. Codon translation uses the following gene tracks as the basis for translation, depending on the species chosen (Table 2). Species listed in the row labeled "None" do not have species-specific reading frames for gene translation. Gene TrackSpecies Known Geneshuman, mouse Ensembl Genes v60 zebrafish, medaka, stickleback, tetraodon, fugu, x. tropicalis (frog) Table 2. Gene tracks used for codon translation. Methods Pairwise alignments with the zebrafish genome were generated for each species using lastz from repeat-masked genomic sequence. Pairwise alignments were then linked into chains using a dynamic programming algorithm that finds maximally scoring chains of gapless subsections of the alignments organized in a kd-tree. The scoring matrix and parameters for pairwise alignment and chaining were tuned for each species based on phylogenetic distance from the reference. High-scoring chains were then placed along the genome, with gaps filled by lower-scoring chains, to produce an alignment net. For more information about the chaining and netting process and parameters for each species, see the description pages for the Chain and Net tracks. The resulting best-in-genome pairwise alignments were progressively aligned using multiz/autoMZ, following the tree topology diagrammed above, to produce multiple alignments. The multiple alignments were post-processed to add annotations indicating alignment gaps, genomic breaks, and base quality of the component sequences. The annotated multiple alignments, in MAF format, are available for bulk download. An alignment summary table containing an entry for each alignment block in each species was generated to improve track display performance at large scales. Framing tables were constructed to enable visualization of codons in the multiple alignment display. Phylogenetic Tree Model Both phastCons and phyloP are phylogenetic methods that rely on a tree model containing the tree topology, branch lengths representing evolutionary distance at neutrally evolving sites, the background distribution of nucleotides, and a substitution rate matrix. The vertebrate tree model for this track was generated using the phyloFit program from the PHAST package (REV model, EM algorithm, medium precision) using multiple alignments of 4-fold degenerate sites extracted from the 8way alignment (msa_view). The 4d sites were derived from the RefSeq (coding) gene set, filtered to select single-coverage long transcripts. The fish subset tree model was extracted from the vertebrate model. PhastCons Conservation The phastCons program computes conservation scores based on a phylo-HMM, a type of probabilistic model that describes both the process of DNA substitution at each site in a genome and the way this process changes from one site to the next (Felsenstein and Churchill 1996, Yang 1995, Siepel and Haussler 2005). PhastCons uses a two-state phylo-HMM, with a state for conserved regions and a state for non-conserved regions. The value plotted at each site is the posterior probability that the corresponding alignment column was "generated" by the conserved state of the phylo-HMM. These scores reflect the phylogeny (including branch lengths) of the species in question, a continuous-time Markov model of the nucleotide substitution process, and a tendency for conservation levels to be autocorrelated along the genome (i.e., to be similar at adjacent sites). The general reversible (REV) substitution model was used. Unlike many conservation-scoring programs, phastCons does not rely on a sliding window of fixed size; therefore, short highly-conserved regions and long moderately conserved regions can both obtain high scores. More information about phastCons can be found in Siepel et al. 2005. The phastCons parameters used were: --expected-length=45, --target-coverage=0.3 and --rho=0.3 in both the veterbrate and fish subset operations. PhyloP Conservation The phyloP program supports several different methods for computing p-values of conservation or acceleration, for individual nucleotides or larger elements ( http://compgen.cshl.edu/phast/). Here it was used to produce separate scores at each base (--wig-scores option), considering all branches of the phylogeny rather than a particular subtree or lineage (i.e., the --subtree option was not used). The scores were computed by performing a likelihood ratio test at each alignment column (--method LRT), and scores for both conservation and acceleration were produced (--mode CONACC). Conserved Elements The conserved elements were predicted by running phastCons with the --most-conserved (== --viterbi) option. The predicted elements are segments of the alignment that are likely to have been "generated" by the conserved state of the phylo-HMM. Each element is assigned a log-odds score equal to its log probability under the conserved model minus its log probability under the non-conserved model. The "score" field associated with this track contains transformed log-odds scores, taking values between 0 and 1000. (The scores are transformed using a monotonic function of the form a * log(x) + b.) The raw log odds scores are retained in the "name" field and can be seen on the details page or in the browser when the track's display mode is set to "pack" or "full". Credits This track was created using the following programs: Alignment tools: lastz (formerly blastz) and multiz by Minmei Hou, Scott Schwartz and Webb Miller of the Penn State Bioinformatics Group Chaining and Netting: axtChain, chainNet by Jim Kent at UCSC Conservation scoring: phastCons, phyloP, phyloFit, tree_doctor, msa_view and other programs in PHAST by Adam Siepel at Cold Spring Harbor Laboratory (original development done at the Haussler lab at UCSC). MAF Annotation tools: mafAddIRows by Brian Raney, UCSC; mafAddQRows by Richard Burhans, Penn State; genePredToMafFrames by Mark Diekhans, UCSC Tree image generator: phyloPng by Galt Barber, UCSC Conservation track display: Kate Rosenbloom, Hiram Clawson (wiggle display), and Brian Raney (gap annotation and codon framing) at UCSC The phylogenetic tree is based on Murphy et al. (2001) and general consensus in the vertebrate phylogeny community as of March 2007. References Phylo-HMMs, phastCons, and phyloP: Felsenstein J, Churchill GA. A Hidden Markov Model approach to variation among sites in rate of evolution. Mol Biol Evol. 1996 Jan;13(1):93-104. PMID: 8583911 Pollard KS, Hubisz MJ, Rosenbloom KR, Siepel A. Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res. 2010 Jan;20(1):110-21. PMID: 19858363; PMC: PMC2798823 Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S, et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 2005 Aug;15(8):1034-50. PMID: 16024819; PMC: PMC1182216 Siepel A, Haussler D. Phylogenetic Hidden Markov Models. In: Nielsen R, editor. Statistical Methods in Molecular Evolution. New York: Springer; 2005. pp. 325-351. Yang Z. A space-time process model for the evolution of DNA sequences. Genetics. 1995 Feb;139(2):993-1005. PMID: 7713447; PMC: PMC1206396 Chain/Net: Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9. PMID: 14500911; PMC: PMC208784 Multiz: Blanchette M, Kent WJ, Riemer C, Elnitski L, Smit AF, Roskin KM, Baertsch R, Rosenbloom K, Clawson H, Green ED, et al. Aligning multiple genomic sequences with the threaded blockset aligner. Genome Res. 2004 Apr;14(4):708-15. PMID: 15060014; PMC: PMC383317 Lastz (formerly Blastz): Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002:115-26. PMID: 11928468 Harris RS. Improved pairwise alignment of genomic DNA. Ph.D. Thesis. Pennsylvania State University, USA. 2007. Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-mouse alignments with BLASTZ. Genome Res. 2003 Jan;13(1):103-7. PMID: 12529312; PMC: PMC430961 Phylogenetic Tree: Murphy WJ, Eizirik E, O'Brien SJ, Madsen O, Scally M, Douady CJ, Teeling E, Ryder OA, Stanhope MJ, de Jong WW, Springer MS. Resolution of the early placental mammal radiation using Bayesian phylogenetics. Science. 2001 Dec 14;294(5550):2348-51. PMID: 11743200 cons8wayViewalign Multiz Alignments Multiz Alignment & Conservation (8 Species) Comparative Genomics multiz8way Multiz Align Multiz Alignments & Conservation (8 species) Comparative Genomics cons8wayViewphastcons Element Conservation (phastCons) Multiz Alignment & Conservation (8 Species) Comparative Genomics phastCons8way Vertebrate Cons Vertebrate Conservation by PhastCons (8 species) Comparative Genomics phastCons8wayFish Fish Cons Fish Conservation by PhastCons (5 species) Comparative Genomics cons8wayViewelements Conserved Elements Multiz Alignment & Conservation (8 Species) Comparative Genomics phastConsElements8way Vertebrate El Vertebrate Conserved Elements (8 species) Comparative Genomics phastConsElements8wayFish Fish El Fish Conserved Elements (5 species) Comparative Genomics cons8wayViewphyloP Basewise Conservation (phyloP) Multiz Alignment & Conservation (8 Species) Comparative Genomics phyloP8way Vertebrate Cons Vertebrate Basewise Conservation by PhyloP (8 species) Comparative Genomics phyloP8wayFish Fish Cons Fish Basewise Conservation by PhyloP (5 species) Comparative Genomics fishChainNet Fish Chain/Net Fish Genomes, Chain and Net Alignments Comparative Genomics Description Chain Track The chain track shows alignments of zebrafish (Jul. 2010 (Zv9/danRer7)/danRer7) to other genomes using a gap scoring system that allows longer gaps than traditional affine gap scoring systems. It can also tolerate gaps in both zebrafish and the other genome simultaneously. These "double-sided" gaps can be caused by local inversions and overlapping deletions in both species. The chain track displays boxes joined together by either single or double lines. The boxes represent aligning regions. Single lines indicate gaps that are largely due to a deletion in the other assembly or an insertion in the zebrafish assembly. Double lines represent more complex gaps that involve substantial sequence in both species. This may result from inversions, overlapping deletions, an abundance of local mutation, or an unsequenced gap in one species. In cases where multiple chains align over a particular region of the other genome, the chains with single-lined gaps are often due to processed pseudogenes, while chains with double-lined gaps are more often due to paralogs and unprocessed pseudogenes. In the "pack" and "full" display modes, the individual feature names indicate the chromosome, strand, and location (in thousands) of the match for each matching alignment. Net Track The net track shows the best zebrafish/other chain for every part of the other genome. It is useful for finding orthologous regions and for studying genome rearrangement. The zebrafish sequence used in this annotation is from the Jul. 2010 (Zv9/danRer7) (danRer7) assembly. Display Conventions and Configuration Chain Track By default, the chains to chromosome-based assemblies are colored based on which chromosome they map to in the aligning organism. To turn off the coloring, check the "off" button next to: Color track based on chromosome. To display only the chains of one chromosome in the aligning organism, enter the name of that chromosome (e.g. chr4) in the box next to: Filter by chromosome. Net Track In full display mode, the top-level (level 1) chains are the largest, highest-scoring chains that span this region. In many cases gaps exist in the top-level chain. When possible, these are filled in by other chains that are displayed at level 2. The gaps in level 2 chains may be filled by level 3 chains and so forth. In the graphical display, the boxes represent ungapped alignments; the lines represent gaps. Click on a box to view detailed information about the chain as a whole; click on a line to display information about the gap. The detailed information is useful in determining the cause of the gap or, for lower level chains, the genomic rearrangement. Individual items in the display are categorized as one of four types (other than gap): Top - the best, longest match. Displayed on level 1. Syn - line-ups on the same chromosome as the gap in the level above it. Inv - a line-up on the same chromosome as the gap above it, but in the opposite orientation. NonSyn - a match to a chromosome different from the gap in the level above. Methods Chain track The genome sequences were aligned with lastz. The resulting alignments were converted into axt format using the lavToAxt program. The axt alignments were fed into axtChain, which organizes all alignments between a single zebrafish chromosome and a single chromosome from the other genome into a group and creates a kd-tree out of the gapless subsections (blocks) of the alignments. A dynamic program was then run over the kd-trees to find the maximally scoring chains of these blocks. The following matrix was used:  ACGT A90-330-236-356 C-330100-318-236 G-236-318100-330 T-356-236-33090 Chains scoring below a minimum score of '2000' were discarded; the remaining chains are displayed in this track. The linear gap matrix used with axtChain: -linearGap=medium tableSize 11 smallSize 111 position 1 2 3 11 111 2111 12111 32111 72111 152111 252111 qGap 350 425 450 600 900 2900 22900 57900 117900 217900 317900 tGap 350 425 450 600 900 2900 22900 57900 117900 217900 317900 bothGap 750 825 850 1000 1300 3300 23300 58300 118300 218300 318300 See also: lastz parameters used in these alignments, and chain minimum score and gap parameters used in these alignments. Net track Chains were derived from lastz alignments, using the methods described above for the chain track, and sorted with the highest-scoring chains in the genome ranked first. The program chainNet was then used to place the chains one at a time, trimming them as necessary to fit into sections not already covered by a higher-scoring chain. During this process, a natural hierarchy emerged in which a chain that filled a gap in a higher-scoring chain was placed underneath that chain. The program netSyntenic was used to fill in information about the relationship between higher- and lower-level chains, such as whether a lower-level chain was syntenic or inverted relative to the higher-level chain. The program netClass was then used to fill in how much of the gaps and chains contained Ns (sequencing gaps) in one or both species and how much was filled with transposons inserted before and after the two organisms diverged. Credits Lastz (previously known as blastz) was developed at Pennsylvania State University by Minmei Hou, Scott Schwartz, Zheng Zhang, and Webb Miller with advice from Ross Hardison. The axtChain program was developed at the University of California at Santa Cruz by Jim Kent with advice from Webb Miller and David Haussler. The browser display and database storage of the chains and nets were created by Robert Baertsch and Jim Kent. The chainNet, netSyntenic, and netClass programs were developed at the University of California Santa Cruz by Jim Kent. References Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002;:115-26. Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9. Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-Mouse Alignments with BLASTZ. Genome Res. 2003 Jan;13(1):103-7. fishChainNetViewnet Nets Fish Genomes, Chain and Net Alignments Comparative Genomics netTetNig2 Tetraodon Net Tetraodon (Mar. 2007 (Genoscope 8.0/tetNig2)) Alignment Net Comparative Genomics netGasAcu1 Stickleback Net Stickleback (Feb. 2006 (Broad/gasAcu1)) Alignment Net Comparative Genomics netOryLat2 Medaka Net Medaka (Oct. 2005 (NIG/UT MEDAKA1/oryLat2)) Alignment Net Comparative Genomics netFr3 Fugu Net Fugu (Oct. 2011 (FUGU5/fr3)) Alignment Net Comparative Genomics fishChainNetViewchain Chains Fish Genomes, Chain and Net Alignments Comparative Genomics chainTetNig2 Tetraodon Chain Tetraodon (Mar. 2007 (Genoscope 8.0/tetNig2)) Chained Alignments Comparative Genomics chainGasAcu1 Stickleback Chain Stickleback (Feb. 2006 (Broad/gasAcu1)) Chained Alignments Comparative Genomics chainOryLat2 Medaka Chain Medaka (Oct. 2005 (NIG/UT MEDAKA1/oryLat2)) Chained Alignments Comparative Genomics chainFr3 Fugu Chain Fugu (Oct. 2011 (FUGU5/fr3)) Chained Alignments Comparative Genomics vertebrateChainNet Vertebrate Chain/Net Vertebrate Genomes, Chain and Net Alignments Comparative Genomics Description Chain Track The chain track shows alignments of zebrafish (Jul. 2010 (Zv9/danRer7)/danRer7) to other genomes using a gap scoring system that allows longer gaps than traditional affine gap scoring systems. It can also tolerate gaps in both zebrafish and the other genome simultaneously. These "double-sided" gaps can be caused by local inversions and overlapping deletions in both species. The chain track displays boxes joined together by either single or double lines. The boxes represent aligning regions. Single lines indicate gaps that are largely due to a deletion in the other assembly or an insertion in the zebrafish assembly. Double lines represent more complex gaps that involve substantial sequence in both species. This may result from inversions, overlapping deletions, an abundance of local mutation, or an unsequenced gap in one species. In cases where multiple chains align over a particular region of the other genome, the chains with single-lined gaps are often due to processed pseudogenes, while chains with double-lined gaps are more often due to paralogs and unprocessed pseudogenes. In the "pack" and "full" display modes, the individual feature names indicate the chromosome, strand, and location (in thousands) of the match for each matching alignment. Net Track The net track shows the best zebrafish/other chain for every part of the other genome. It is useful for finding orthologous regions and for studying genome rearrangement. The zebrafish sequence used in this annotation is from the Jul. 2010 (Zv9/danRer7) (danRer7) assembly. Display Conventions and Configuration Chain Track By default, the chains to chromosome-based assemblies are colored based on which chromosome they map to in the aligning organism. To turn off the coloring, check the "off" button next to: Color track based on chromosome. To display only the chains of one chromosome in the aligning organism, enter the name of that chromosome (e.g. chr4) in the box next to: Filter by chromosome. Net Track In full display mode, the top-level (level 1) chains are the largest, highest-scoring chains that span this region. In many cases gaps exist in the top-level chain. When possible, these are filled in by other chains that are displayed at level 2. The gaps in level 2 chains may be filled by level 3 chains and so forth. In the graphical display, the boxes represent ungapped alignments; the lines represent gaps. Click on a box to view detailed information about the chain as a whole; click on a line to display information about the gap. The detailed information is useful in determining the cause of the gap or, for lower level chains, the genomic rearrangement. Individual items in the display are categorized as one of four types (other than gap): Top - the best, longest match. Displayed on level 1. Syn - line-ups on the same chromosome as the gap in the level above it. Inv - a line-up on the same chromosome as the gap above it, but in the opposite orientation. NonSyn - a match to a chromosome different from the gap in the level above. Methods Chain track The genome sequences were aligned with lastz. The resulting alignments were converted into axt format using the lavToAxt program. The axt alignments were fed into axtChain, which organizes all alignments between a single zebrafish chromosome and a single chromosome from the other genome into a group and creates a kd-tree out of the gapless subsections (blocks) of the alignments. A dynamic program was then run over the kd-trees to find the maximally scoring chains of these blocks. The following matrix was used:  ACGT A90-330-236-356 C-330100-318-236 G-236-318100-330 T-356-236-33090 Chains scoring below a minimum score of '5000' were discarded; the remaining chains are displayed in this track. The linear gap matrix used with axtChain: -linearGap=loose tablesize 11 smallSize 111 position 1 2 3 11 111 2111 12111 32111 72111 152111 252111 qGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 tGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 bothGap 625 660 700 750 900 1400 4000 8000 16000 32000 57000 See also: lastz parameters used in these alignments, and chain minimum score and gap parameters used in these alignments. Net track Chains were derived from lastz alignments, using the methods described above for the chain track, and sorted with the highest-scoring chains in the genome ranked first. The program chainNet was then used to place the chains one at a time, trimming them as necessary to fit into sections not already covered by a higher-scoring chain. During this process, a natural hierarchy emerged in which a chain that filled a gap in a higher-scoring chain was placed underneath that chain. The program netSyntenic was used to fill in information about the relationship between higher- and lower-level chains, such as whether a lower-level chain was syntenic or inverted relative to the higher-level chain. The program netClass was then used to fill in how much of the gaps and chains contained Ns (sequencing gaps) in one or both species and how much was filled with transposons inserted before and after the two organisms diverged. Credits Lastz (previously known as blastz) was developed at Pennsylvania State University by Minmei Hou, Scott Schwartz, Zheng Zhang, and Webb Miller with advice from Ross Hardison. The axtChain program was developed at the University of California at Santa Cruz by Jim Kent with advice from Webb Miller and David Haussler. The browser display and database storage of the chains and nets were created by Robert Baertsch and Jim Kent. The chainNet, netSyntenic, and netClass programs were developed at the University of California Santa Cruz by Jim Kent. References Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002;:115-26. Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9. Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-Mouse Alignments with BLASTZ. Genome Res. 2003 Jan;13(1):103-7. vertebrateChainNetViewnet Nets Vertebrate Genomes, Chain and Net Alignments Comparative Genomics netXenTro3 X. tropicalis Net X. tropicalis (Nov. 2009 (JGI 4.2/xenTro3)) Alignment Net Comparative Genomics netMm10 Mouse Net Mouse (Dec. 2011 (GRCm38/mm10)) Alignment Net Comparative Genomics netHg19 Human Net Human (Feb. 2009 (GRCh37/hg19)) Alignment Net Comparative Genomics vertebrateChainNetViewchain Chains Vertebrate Genomes, Chain and Net Alignments Comparative Genomics chainXenTro3 X. tropicalis Chain X. tropicalis (Nov. 2009 (JGI 4.2/xenTro3)) Chained Alignments Comparative Genomics chainMm10 Mouse Chain Mouse (Dec. 2011 (GRCm38/mm10)) Chained Alignments Comparative Genomics chainHg19 Human Chain Human (Feb. 2009 (GRCh37/hg19)) Chained Alignments Comparative Genomics chainNetMelGal1 Turkey Chain/Net Turkey (Dec. 2009 (TGC Turkey_2.01/melGal1)), Chain and Net Alignments Comparative Genomics Description This track shows regions of the genome that are alignable to other genomes ("chain" subtracks) or in synteny ("net" subtracks). The alignable parts are shown with thick blocks that look like exons. Non-alignable parts between these are shown like introns. Chain Track The chain track shows alignments of turkey (Dec. 2009 (TGC Turkey_2.01/melGal1)) to the zebrafish genome using a gap scoring system that allows longer gaps than traditional affine gap scoring systems. It can also tolerate gaps in both turkey and zebrafish simultaneously. These "double-sided" gaps can be caused by local inversions and overlapping deletions in both species. The chain track displays boxes joined together by either single or double lines. The boxes represent aligning regions. Single lines indicate gaps that are largely due to a deletion in the turkey assembly or an insertion in the zebrafish assembly. Double lines represent more complex gaps that involve substantial sequence in both species. This may result from inversions, overlapping deletions, an abundance of local mutation, or an unsequenced gap in one species. In cases where multiple chains align over a particular region of the zebrafish genome, the chains with single-lined gaps are often due to processed pseudogenes, while chains with double-lined gaps are more often due to paralogs and unprocessed pseudogenes. In the "pack" and "full" display modes, the individual feature names indicate the chromosome, strand, and location (in thousands) of the match for each matching alignment. Net Track The net track shows the best turkey/zebrafish chain for every part of the zebrafish genome. It is useful for finding syntenic regions, possibly orthologs, and for studying genome rearrangement. The turkey sequence used in this annotation is from the Dec. 2009 (TGC Turkey_2.01/melGal1) assembly. Display Conventions and Configuration Chain Track By default, the chains to chromosome-based assemblies are colored based on which chromosome they map to in the aligning organism. To turn off the coloring, check the "off" button next to: Color track based on chromosome. To display only the chains of one chromosome in the aligning organism, enter the name of that chromosome (e.g. chr4) in box next to: Filter by chromosome. Net Track In full display mode, the top-level (level 1) chains are the largest, highest-scoring chains that span this region. In many cases gaps exist in the top-level chain. When possible, these are filled in by other chains that are displayed at level 2. The gaps in level 2 chains may be filled by level 3 chains and so forth. In the graphical display, the boxes represent ungapped alignments; the lines represent gaps. Click on a box to view detailed information about the chain as a whole; click on a line to display information about the gap. The detailed information is useful in determining the cause of the gap or, for lower level chains, the genomic rearrangement. Individual items in the display are categorized as one of four types (other than gap): Top - the best, longest match. Displayed on level 1. Syn - line-ups on the same chromosome as the gap in the level above it. Inv - a line-up on the same chromosome as the gap above it, but in the opposite orientation. NonSyn - a match to a chromosome different from the gap in the level above. Methods Chain track Transposons that have been inserted since the turkey/zebrafish split were removed from the assemblies. The abbreviated genomes were aligned with lastz, and the transposons were added back in. The resulting alignments were converted into axt format using the lavToAxt program. The axt alignments were fed into axtChain, which organizes all alignments between a single turkey chromosome and a single zebrafish chromosome into a group and creates a kd-tree out of the gapless subsections (blocks) of the alignments. A dynamic program was then run over the kd-trees to find the maximally scoring chains of these blocks. The following matrix was used:  ACGT A91-114-31-123 C-114100-125-31 G-31-125100-114 T-123-31-11491 Chains scoring below a minimum score of "5000" were discarded; the remaining chains are displayed in this track. The linear gap matrix used with axtChain: -linearGap=loose tablesize 11 smallSize 111 position 1 2 3 11 111 2111 12111 32111 72111 152111 252111 qGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 tGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 bothGap 625 660 700 750 900 1400 4000 8000 16000 32000 57000 Net track Chains were derived from lastz alignments, using the methods described on the chain tracks description pages, and sorted with the highest-scoring chains in the genome ranked first. The program chainNet was then used to place the chains one at a time, trimming them as necessary to fit into sections not already covered by a higher-scoring chain. During this process, a natural hierarchy emerged in which a chain that filled a gap in a higher-scoring chain was placed underneath that chain. The program netSyntenic was used to fill in information about the relationship between higher- and lower-level chains, such as whether a lower-level chain was syntenic or inverted relative to the higher-level chain. The program netClass was then used to fill in how much of the gaps and chains contained Ns (sequencing gaps) in one or both species and how much was filled with transposons inserted before and after the two organisms diverged. Credits Lastz (previously known as blastz) was developed at Pennsylvania State University by Minmei Hou, Scott Schwartz, Zheng Zhang, and Webb Miller with advice from Ross Hardison. Lineage-specific repeats were identified by Arian Smit and his RepeatMasker program. The axtChain program was developed at the University of California at Santa Cruz by Jim Kent with advice from Webb Miller and David Haussler. The browser display and database storage of the chains and nets were created by Robert Baertsch and Jim Kent. The chainNet, netSyntenic, and netClass programs were developed at the University of California Santa Cruz by Jim Kent. References Harris, R.S. (2007) Improved pairwise alignment of genomic DNA Ph.D. Thesis, The Pennsylvania State University Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002:115-26. PMID: 11928468 Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9. PMID: 14500911; PMC: PMC208784 Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-mouse alignments with BLASTZ. Genome Res. 2003 Jan;13(1):103-7. PMID: 12529312; PMC: PMC430961 chainNetMelGal1Viewnet Net Turkey (Dec. 2009 (TGC Turkey_2.01/melGal1)), Chain and Net Alignments Comparative Genomics netMelGal1 Turkey Net Turkey (Dec. 2009 (TGC Turkey_2.01/melGal1)) Alignment Net Comparative Genomics Description This track shows regions of the genome that are alignable to other genomes ("chain" subtracks) or in synteny ("net" subtracks). The alignable parts are shown with thick blocks that look like exons. Non-alignable parts between these are shown like introns. Chain Track The chain track shows alignments of turkey (Dec. 2009 (TGC Turkey_2.01/melGal1)) to the zebrafish genome using a gap scoring system that allows longer gaps than traditional affine gap scoring systems. It can also tolerate gaps in both turkey and zebrafish simultaneously. These "double-sided" gaps can be caused by local inversions and overlapping deletions in both species. The chain track displays boxes joined together by either single or double lines. The boxes represent aligning regions. Single lines indicate gaps that are largely due to a deletion in the turkey assembly or an insertion in the zebrafish assembly. Double lines represent more complex gaps that involve substantial sequence in both species. This may result from inversions, overlapping deletions, an abundance of local mutation, or an unsequenced gap in one species. In cases where multiple chains align over a particular region of the zebrafish genome, the chains with single-lined gaps are often due to processed pseudogenes, while chains with double-lined gaps are more often due to paralogs and unprocessed pseudogenes. In the "pack" and "full" display modes, the individual feature names indicate the chromosome, strand, and location (in thousands) of the match for each matching alignment. Net Track The net track shows the best turkey/zebrafish chain for every part of the zebrafish genome. It is useful for finding syntenic regions, possibly orthologs, and for studying genome rearrangement. The turkey sequence used in this annotation is from the Dec. 2009 (TGC Turkey_2.01/melGal1) assembly. Display Conventions and Configuration Chain Track By default, the chains to chromosome-based assemblies are colored based on which chromosome they map to in the aligning organism. To turn off the coloring, check the "off" button next to: Color track based on chromosome. To display only the chains of one chromosome in the aligning organism, enter the name of that chromosome (e.g. chr4) in box next to: Filter by chromosome. Net Track In full display mode, the top-level (level 1) chains are the largest, highest-scoring chains that span this region. In many cases gaps exist in the top-level chain. When possible, these are filled in by other chains that are displayed at level 2. The gaps in level 2 chains may be filled by level 3 chains and so forth. In the graphical display, the boxes represent ungapped alignments; the lines represent gaps. Click on a box to view detailed information about the chain as a whole; click on a line to display information about the gap. The detailed information is useful in determining the cause of the gap or, for lower level chains, the genomic rearrangement. Individual items in the display are categorized as one of four types (other than gap): Top - the best, longest match. Displayed on level 1. Syn - line-ups on the same chromosome as the gap in the level above it. Inv - a line-up on the same chromosome as the gap above it, but in the opposite orientation. NonSyn - a match to a chromosome different from the gap in the level above. Methods Chain track Transposons that have been inserted since the turkey/zebrafish split were removed from the assemblies. The abbreviated genomes were aligned with lastz, and the transposons were added back in. The resulting alignments were converted into axt format using the lavToAxt program. The axt alignments were fed into axtChain, which organizes all alignments between a single turkey chromosome and a single zebrafish chromosome into a group and creates a kd-tree out of the gapless subsections (blocks) of the alignments. A dynamic program was then run over the kd-trees to find the maximally scoring chains of these blocks. The following matrix was used:  ACGT A91-114-31-123 C-114100-125-31 G-31-125100-114 T-123-31-11491 Chains scoring below a minimum score of "5000" were discarded; the remaining chains are displayed in this track. The linear gap matrix used with axtChain: -linearGap=loose tablesize 11 smallSize 111 position 1 2 3 11 111 2111 12111 32111 72111 152111 252111 qGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 tGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 bothGap 625 660 700 750 900 1400 4000 8000 16000 32000 57000 Net track Chains were derived from lastz alignments, using the methods described on the chain tracks description pages, and sorted with the highest-scoring chains in the genome ranked first. The program chainNet was then used to place the chains one at a time, trimming them as necessary to fit into sections not already covered by a higher-scoring chain. During this process, a natural hierarchy emerged in which a chain that filled a gap in a higher-scoring chain was placed underneath that chain. The program netSyntenic was used to fill in information about the relationship between higher- and lower-level chains, such as whether a lower-level chain was syntenic or inverted relative to the higher-level chain. The program netClass was then used to fill in how much of the gaps and chains contained Ns (sequencing gaps) in one or both species and how much was filled with transposons inserted before and after the two organisms diverged. Credits Lastz (previously known as blastz) was developed at Pennsylvania State University by Minmei Hou, Scott Schwartz, Zheng Zhang, and Webb Miller with advice from Ross Hardison. Lineage-specific repeats were identified by Arian Smit and his RepeatMasker program. The axtChain program was developed at the University of California at Santa Cruz by Jim Kent with advice from Webb Miller and David Haussler. The browser display and database storage of the chains and nets were created by Robert Baertsch and Jim Kent. The chainNet, netSyntenic, and netClass programs were developed at the University of California Santa Cruz by Jim Kent. References Harris, R.S. (2007) Improved pairwise alignment of genomic DNA Ph.D. Thesis, The Pennsylvania State University Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002:115-26. PMID: 11928468 Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9. PMID: 14500911; PMC: PMC208784 Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-mouse alignments with BLASTZ. Genome Res. 2003 Jan;13(1):103-7. PMID: 12529312; PMC: PMC430961 chainNetMelGal1Viewchain Chain Turkey (Dec. 2009 (TGC Turkey_2.01/melGal1)), Chain and Net Alignments Comparative Genomics chainMelGal1 Turkey Chain Turkey (Dec. 2009 (TGC Turkey_2.01/melGal1)) Chained Alignments Comparative Genomics Description This track shows regions of the genome that are alignable to other genomes ("chain" subtracks) or in synteny ("net" subtracks). The alignable parts are shown with thick blocks that look like exons. Non-alignable parts between these are shown like introns. Chain Track The chain track shows alignments of turkey (Dec. 2009 (TGC Turkey_2.01/melGal1)) to the zebrafish genome using a gap scoring system that allows longer gaps than traditional affine gap scoring systems. It can also tolerate gaps in both turkey and zebrafish simultaneously. These "double-sided" gaps can be caused by local inversions and overlapping deletions in both species. The chain track displays boxes joined together by either single or double lines. The boxes represent aligning regions. Single lines indicate gaps that are largely due to a deletion in the turkey assembly or an insertion in the zebrafish assembly. Double lines represent more complex gaps that involve substantial sequence in both species. This may result from inversions, overlapping deletions, an abundance of local mutation, or an unsequenced gap in one species. In cases where multiple chains align over a particular region of the zebrafish genome, the chains with single-lined gaps are often due to processed pseudogenes, while chains with double-lined gaps are more often due to paralogs and unprocessed pseudogenes. In the "pack" and "full" display modes, the individual feature names indicate the chromosome, strand, and location (in thousands) of the match for each matching alignment. Net Track The net track shows the best turkey/zebrafish chain for every part of the zebrafish genome. It is useful for finding syntenic regions, possibly orthologs, and for studying genome rearrangement. The turkey sequence used in this annotation is from the Dec. 2009 (TGC Turkey_2.01/melGal1) assembly. Display Conventions and Configuration Chain Track By default, the chains to chromosome-based assemblies are colored based on which chromosome they map to in the aligning organism. To turn off the coloring, check the "off" button next to: Color track based on chromosome. To display only the chains of one chromosome in the aligning organism, enter the name of that chromosome (e.g. chr4) in box next to: Filter by chromosome. Net Track In full display mode, the top-level (level 1) chains are the largest, highest-scoring chains that span this region. In many cases gaps exist in the top-level chain. When possible, these are filled in by other chains that are displayed at level 2. The gaps in level 2 chains may be filled by level 3 chains and so forth. In the graphical display, the boxes represent ungapped alignments; the lines represent gaps. Click on a box to view detailed information about the chain as a whole; click on a line to display information about the gap. The detailed information is useful in determining the cause of the gap or, for lower level chains, the genomic rearrangement. Individual items in the display are categorized as one of four types (other than gap): Top - the best, longest match. Displayed on level 1. Syn - line-ups on the same chromosome as the gap in the level above it. Inv - a line-up on the same chromosome as the gap above it, but in the opposite orientation. NonSyn - a match to a chromosome different from the gap in the level above. Methods Chain track Transposons that have been inserted since the turkey/zebrafish split were removed from the assemblies. The abbreviated genomes were aligned with lastz, and the transposons were added back in. The resulting alignments were converted into axt format using the lavToAxt program. The axt alignments were fed into axtChain, which organizes all alignments between a single turkey chromosome and a single zebrafish chromosome into a group and creates a kd-tree out of the gapless subsections (blocks) of the alignments. A dynamic program was then run over the kd-trees to find the maximally scoring chains of these blocks. The following matrix was used:  ACGT A91-114-31-123 C-114100-125-31 G-31-125100-114 T-123-31-11491 Chains scoring below a minimum score of "5000" were discarded; the remaining chains are displayed in this track. The linear gap matrix used with axtChain: -linearGap=loose tablesize 11 smallSize 111 position 1 2 3 11 111 2111 12111 32111 72111 152111 252111 qGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 tGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 bothGap 625 660 700 750 900 1400 4000 8000 16000 32000 57000 Net track Chains were derived from lastz alignments, using the methods described on the chain tracks description pages, and sorted with the highest-scoring chains in the genome ranked first. The program chainNet was then used to place the chains one at a time, trimming them as necessary to fit into sections not already covered by a higher-scoring chain. During this process, a natural hierarchy emerged in which a chain that filled a gap in a higher-scoring chain was placed underneath that chain. The program netSyntenic was used to fill in information about the relationship between higher- and lower-level chains, such as whether a lower-level chain was syntenic or inverted relative to the higher-level chain. The program netClass was then used to fill in how much of the gaps and chains contained Ns (sequencing gaps) in one or both species and how much was filled with transposons inserted before and after the two organisms diverged. Credits Lastz (previously known as blastz) was developed at Pennsylvania State University by Minmei Hou, Scott Schwartz, Zheng Zhang, and Webb Miller with advice from Ross Hardison. Lineage-specific repeats were identified by Arian Smit and his RepeatMasker program. The axtChain program was developed at the University of California at Santa Cruz by Jim Kent with advice from Webb Miller and David Haussler. The browser display and database storage of the chains and nets were created by Robert Baertsch and Jim Kent. The chainNet, netSyntenic, and netClass programs were developed at the University of California Santa Cruz by Jim Kent. References Harris, R.S. (2007) Improved pairwise alignment of genomic DNA Ph.D. Thesis, The Pennsylvania State University Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002:115-26. PMID: 11928468 Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9. PMID: 14500911; PMC: PMC208784 Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-mouse alignments with BLASTZ. Genome Res. 2003 Jan;13(1):103-7. PMID: 12529312; PMC: PMC430961 chainNetPanTro3 Chimp Chain/Net Chimp (Oct. 2010 (CGSC 2.1.3/panTro3)), Chain and Net Alignments Comparative Genomics Description This track shows regions of the genome that are alignable to other genomes ("chain" subtracks) or in synteny ("net" subtracks). The alignable parts are shown with thick blocks that look like exons. Non-alignable parts between these are shown like introns. Chain Track The chain track shows alignments of chimp (Oct. 2010 (CGSC 2.1.3/panTro3)) to the zebrafish genome using a gap scoring system that allows longer gaps than traditional affine gap scoring systems. It can also tolerate gaps in both chimp and zebrafish simultaneously. These "double-sided" gaps can be caused by local inversions and overlapping deletions in both species. The chain track displays boxes joined together by either single or double lines. The boxes represent aligning regions. Single lines indicate gaps that are largely due to a deletion in the chimp assembly or an insertion in the zebrafish assembly. Double lines represent more complex gaps that involve substantial sequence in both species. This may result from inversions, overlapping deletions, an abundance of local mutation, or an unsequenced gap in one species. In cases where multiple chains align over a particular region of the zebrafish genome, the chains with single-lined gaps are often due to processed pseudogenes, while chains with double-lined gaps are more often due to paralogs and unprocessed pseudogenes. In the "pack" and "full" display modes, the individual feature names indicate the chromosome, strand, and location (in thousands) of the match for each matching alignment. Net Track The net track shows the best chimp/zebrafish chain for every part of the zebrafish genome. It is useful for finding syntenic regions, possibly orthologs, and for studying genome rearrangement. The chimp sequence used in this annotation is from the Oct. 2010 (CGSC 2.1.3/panTro3) assembly. Display Conventions and Configuration Chain Track By default, the chains to chromosome-based assemblies are colored based on which chromosome they map to in the aligning organism. To turn off the coloring, check the "off" button next to: Color track based on chromosome. To display only the chains of one chromosome in the aligning organism, enter the name of that chromosome (e.g. chr4) in box next to: Filter by chromosome. Net Track In full display mode, the top-level (level 1) chains are the largest, highest-scoring chains that span this region. In many cases gaps exist in the top-level chain. When possible, these are filled in by other chains that are displayed at level 2. The gaps in level 2 chains may be filled by level 3 chains and so forth. In the graphical display, the boxes represent ungapped alignments; the lines represent gaps. Click on a box to view detailed information about the chain as a whole; click on a line to display information about the gap. The detailed information is useful in determining the cause of the gap or, for lower level chains, the genomic rearrangement. Individual items in the display are categorized as one of four types (other than gap): Top - the best, longest match. Displayed on level 1. Syn - line-ups on the same chromosome as the gap in the level above it. Inv - a line-up on the same chromosome as the gap above it, but in the opposite orientation. NonSyn - a match to a chromosome different from the gap in the level above. Methods Chain track Transposons that have been inserted since the chimp/zebrafish split were removed from the assemblies. The abbreviated genomes were aligned with lastz, and the transposons were added back in. The resulting alignments were converted into axt format using the lavToAxt program. The axt alignments were fed into axtChain, which organizes all alignments between a single chimp chromosome and a single zebrafish chromosome into a group and creates a kd-tree out of the gapless subsections (blocks) of the alignments. A dynamic program was then run over the kd-trees to find the maximally scoring chains of these blocks. The following matrix was used:  ACGT A91-90-25-100 C-90100-100-25 G-25-100100-90 T-100-25-9091 Chains scoring below a minimum score of "5000" were discarded; the remaining chains are displayed in this track. The linear gap matrix used with axtChain: -linearGap=loose tablesize 11 smallSize 111 position 1 2 3 11 111 2111 12111 32111 72111 152111 252111 qGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 tGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 bothGap 625 660 700 750 900 1400 4000 8000 16000 32000 57000 Net track Chains were derived from lastz alignments, using the methods described on the chain tracks description pages, and sorted with the highest-scoring chains in the genome ranked first. The program chainNet was then used to place the chains one at a time, trimming them as necessary to fit into sections not already covered by a higher-scoring chain. During this process, a natural hierarchy emerged in which a chain that filled a gap in a higher-scoring chain was placed underneath that chain. The program netSyntenic was used to fill in information about the relationship between higher- and lower-level chains, such as whether a lower-level chain was syntenic or inverted relative to the higher-level chain. The program netClass was then used to fill in how much of the gaps and chains contained Ns (sequencing gaps) in one or both species and how much was filled with transposons inserted before and after the two organisms diverged. Credits Lastz (previously known as blastz) was developed at Pennsylvania State University by Minmei Hou, Scott Schwartz, Zheng Zhang, and Webb Miller with advice from Ross Hardison. Lineage-specific repeats were identified by Arian Smit and his RepeatMasker program. The axtChain program was developed at the University of California at Santa Cruz by Jim Kent with advice from Webb Miller and David Haussler. The browser display and database storage of the chains and nets were created by Robert Baertsch and Jim Kent. The chainNet, netSyntenic, and netClass programs were developed at the University of California Santa Cruz by Jim Kent. References Harris, R.S. (2007) Improved pairwise alignment of genomic DNA Ph.D. Thesis, The Pennsylvania State University Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002:115-26. PMID: 11928468 Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9. PMID: 14500911; PMC: PMC208784 Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-mouse alignments with BLASTZ. Genome Res. 2003 Jan;13(1):103-7. PMID: 12529312; PMC: PMC430961 chainNetPanTro3Viewnet Net Chimp (Oct. 2010 (CGSC 2.1.3/panTro3)), Chain and Net Alignments Comparative Genomics netPanTro3 Chimp Net Chimp (Oct. 2010 (CGSC 2.1.3/panTro3)) Alignment net Comparative Genomics Description This track shows regions of the genome that are alignable to other genomes ("chain" subtracks) or in synteny ("net" subtracks). The alignable parts are shown with thick blocks that look like exons. Non-alignable parts between these are shown like introns. Chain Track The chain track shows alignments of chimp (Oct. 2010 (CGSC 2.1.3/panTro3)) to the zebrafish genome using a gap scoring system that allows longer gaps than traditional affine gap scoring systems. It can also tolerate gaps in both chimp and zebrafish simultaneously. These "double-sided" gaps can be caused by local inversions and overlapping deletions in both species. The chain track displays boxes joined together by either single or double lines. The boxes represent aligning regions. Single lines indicate gaps that are largely due to a deletion in the chimp assembly or an insertion in the zebrafish assembly. Double lines represent more complex gaps that involve substantial sequence in both species. This may result from inversions, overlapping deletions, an abundance of local mutation, or an unsequenced gap in one species. In cases where multiple chains align over a particular region of the zebrafish genome, the chains with single-lined gaps are often due to processed pseudogenes, while chains with double-lined gaps are more often due to paralogs and unprocessed pseudogenes. In the "pack" and "full" display modes, the individual feature names indicate the chromosome, strand, and location (in thousands) of the match for each matching alignment. Net Track The net track shows the best chimp/zebrafish chain for every part of the zebrafish genome. It is useful for finding syntenic regions, possibly orthologs, and for studying genome rearrangement. The chimp sequence used in this annotation is from the Oct. 2010 (CGSC 2.1.3/panTro3) assembly. Display Conventions and Configuration Chain Track By default, the chains to chromosome-based assemblies are colored based on which chromosome they map to in the aligning organism. To turn off the coloring, check the "off" button next to: Color track based on chromosome. To display only the chains of one chromosome in the aligning organism, enter the name of that chromosome (e.g. chr4) in box next to: Filter by chromosome. Net Track In full display mode, the top-level (level 1) chains are the largest, highest-scoring chains that span this region. In many cases gaps exist in the top-level chain. When possible, these are filled in by other chains that are displayed at level 2. The gaps in level 2 chains may be filled by level 3 chains and so forth. In the graphical display, the boxes represent ungapped alignments; the lines represent gaps. Click on a box to view detailed information about the chain as a whole; click on a line to display information about the gap. The detailed information is useful in determining the cause of the gap or, for lower level chains, the genomic rearrangement. Individual items in the display are categorized as one of four types (other than gap): Top - the best, longest match. Displayed on level 1. Syn - line-ups on the same chromosome as the gap in the level above it. Inv - a line-up on the same chromosome as the gap above it, but in the opposite orientation. NonSyn - a match to a chromosome different from the gap in the level above. Methods Chain track Transposons that have been inserted since the chimp/zebrafish split were removed from the assemblies. The abbreviated genomes were aligned with lastz, and the transposons were added back in. The resulting alignments were converted into axt format using the lavToAxt program. The axt alignments were fed into axtChain, which organizes all alignments between a single chimp chromosome and a single zebrafish chromosome into a group and creates a kd-tree out of the gapless subsections (blocks) of the alignments. A dynamic program was then run over the kd-trees to find the maximally scoring chains of these blocks. The following matrix was used:  ACGT A91-90-25-100 C-90100-100-25 G-25-100100-90 T-100-25-9091 Chains scoring below a minimum score of "5000" were discarded; the remaining chains are displayed in this track. The linear gap matrix used with axtChain: -linearGap=loose tablesize 11 smallSize 111 position 1 2 3 11 111 2111 12111 32111 72111 152111 252111 qGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 tGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 bothGap 625 660 700 750 900 1400 4000 8000 16000 32000 57000 Net track Chains were derived from lastz alignments, using the methods described on the chain tracks description pages, and sorted with the highest-scoring chains in the genome ranked first. The program chainNet was then used to place the chains one at a time, trimming them as necessary to fit into sections not already covered by a higher-scoring chain. During this process, a natural hierarchy emerged in which a chain that filled a gap in a higher-scoring chain was placed underneath that chain. The program netSyntenic was used to fill in information about the relationship between higher- and lower-level chains, such as whether a lower-level chain was syntenic or inverted relative to the higher-level chain. The program netClass was then used to fill in how much of the gaps and chains contained Ns (sequencing gaps) in one or both species and how much was filled with transposons inserted before and after the two organisms diverged. Credits Lastz (previously known as blastz) was developed at Pennsylvania State University by Minmei Hou, Scott Schwartz, Zheng Zhang, and Webb Miller with advice from Ross Hardison. Lineage-specific repeats were identified by Arian Smit and his RepeatMasker program. The axtChain program was developed at the University of California at Santa Cruz by Jim Kent with advice from Webb Miller and David Haussler. The browser display and database storage of the chains and nets were created by Robert Baertsch and Jim Kent. The chainNet, netSyntenic, and netClass programs were developed at the University of California Santa Cruz by Jim Kent. References Harris, R.S. (2007) Improved pairwise alignment of genomic DNA Ph.D. Thesis, The Pennsylvania State University Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002:115-26. PMID: 11928468 Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9. PMID: 14500911; PMC: PMC208784 Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-mouse alignments with BLASTZ. Genome Res. 2003 Jan;13(1):103-7. PMID: 12529312; PMC: PMC430961 chainNetPanTro3Viewchain Chain Chimp (Oct. 2010 (CGSC 2.1.3/panTro3)), Chain and Net Alignments Comparative Genomics chainPanTro3 Chimp Chain Chimp (Oct. 2010 (CGSC 2.1.3/panTro3)) Chained Alignments Comparative Genomics Description This track shows regions of the genome that are alignable to other genomes ("chain" subtracks) or in synteny ("net" subtracks). The alignable parts are shown with thick blocks that look like exons. Non-alignable parts between these are shown like introns. Chain Track The chain track shows alignments of chimp (Oct. 2010 (CGSC 2.1.3/panTro3)) to the zebrafish genome using a gap scoring system that allows longer gaps than traditional affine gap scoring systems. It can also tolerate gaps in both chimp and zebrafish simultaneously. These "double-sided" gaps can be caused by local inversions and overlapping deletions in both species. The chain track displays boxes joined together by either single or double lines. The boxes represent aligning regions. Single lines indicate gaps that are largely due to a deletion in the chimp assembly or an insertion in the zebrafish assembly. Double lines represent more complex gaps that involve substantial sequence in both species. This may result from inversions, overlapping deletions, an abundance of local mutation, or an unsequenced gap in one species. In cases where multiple chains align over a particular region of the zebrafish genome, the chains with single-lined gaps are often due to processed pseudogenes, while chains with double-lined gaps are more often due to paralogs and unprocessed pseudogenes. In the "pack" and "full" display modes, the individual feature names indicate the chromosome, strand, and location (in thousands) of the match for each matching alignment. Net Track The net track shows the best chimp/zebrafish chain for every part of the zebrafish genome. It is useful for finding syntenic regions, possibly orthologs, and for studying genome rearrangement. The chimp sequence used in this annotation is from the Oct. 2010 (CGSC 2.1.3/panTro3) assembly. Display Conventions and Configuration Chain Track By default, the chains to chromosome-based assemblies are colored based on which chromosome they map to in the aligning organism. To turn off the coloring, check the "off" button next to: Color track based on chromosome. To display only the chains of one chromosome in the aligning organism, enter the name of that chromosome (e.g. chr4) in box next to: Filter by chromosome. Net Track In full display mode, the top-level (level 1) chains are the largest, highest-scoring chains that span this region. In many cases gaps exist in the top-level chain. When possible, these are filled in by other chains that are displayed at level 2. The gaps in level 2 chains may be filled by level 3 chains and so forth. In the graphical display, the boxes represent ungapped alignments; the lines represent gaps. Click on a box to view detailed information about the chain as a whole; click on a line to display information about the gap. The detailed information is useful in determining the cause of the gap or, for lower level chains, the genomic rearrangement. Individual items in the display are categorized as one of four types (other than gap): Top - the best, longest match. Displayed on level 1. Syn - line-ups on the same chromosome as the gap in the level above it. Inv - a line-up on the same chromosome as the gap above it, but in the opposite orientation. NonSyn - a match to a chromosome different from the gap in the level above. Methods Chain track Transposons that have been inserted since the chimp/zebrafish split were removed from the assemblies. The abbreviated genomes were aligned with lastz, and the transposons were added back in. The resulting alignments were converted into axt format using the lavToAxt program. The axt alignments were fed into axtChain, which organizes all alignments between a single chimp chromosome and a single zebrafish chromosome into a group and creates a kd-tree out of the gapless subsections (blocks) of the alignments. A dynamic program was then run over the kd-trees to find the maximally scoring chains of these blocks. The following matrix was used:  ACGT A91-90-25-100 C-90100-100-25 G-25-100100-90 T-100-25-9091 Chains scoring below a minimum score of "5000" were discarded; the remaining chains are displayed in this track. The linear gap matrix used with axtChain: -linearGap=loose tablesize 11 smallSize 111 position 1 2 3 11 111 2111 12111 32111 72111 152111 252111 qGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 tGap 325 360 400 450 600 1100 3600 7600 15600 31600 56600 bothGap 625 660 700 750 900 1400 4000 8000 16000 32000 57000 Net track Chains were derived from lastz alignments, using the methods described on the chain tracks description pages, and sorted with the highest-scoring chains in the genome ranked first. The program chainNet was then used to place the chains one at a time, trimming them as necessary to fit into sections not already covered by a higher-scoring chain. During this process, a natural hierarchy emerged in which a chain that filled a gap in a higher-scoring chain was placed underneath that chain. The program netSyntenic was used to fill in information about the relationship between higher- and lower-level chains, such as whether a lower-level chain was syntenic or inverted relative to the higher-level chain. The program netClass was then used to fill in how much of the gaps and chains contained Ns (sequencing gaps) in one or both species and how much was filled with transposons inserted before and after the two organisms diverged. Credits Lastz (previously known as blastz) was developed at Pennsylvania State University by Minmei Hou, Scott Schwartz, Zheng Zhang, and Webb Miller with advice from Ross Hardison. Lineage-specific repeats were identified by Arian Smit and his RepeatMasker program. The axtChain program was developed at the University of California at Santa Cruz by Jim Kent with advice from Webb Miller and David Haussler. The browser display and database storage of the chains and nets were created by Robert Baertsch and Jim Kent. The chainNet, netSyntenic, and netClass programs were developed at the University of California Santa Cruz by Jim Kent. References Harris, R.S. (2007) Improved pairwise alignment of genomic DNA Ph.D. Thesis, The Pennsylvania State University Chiaromonte F, Yap VB, Miller W. Scoring pairwise genomic sequence alignments. Pac Symp Biocomput. 2002:115-26. PMID: 11928468 Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9. PMID: 14500911; PMC: PMC208784 Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-mouse alignments with BLASTZ. Genome Res. 2003 Jan;13(1):103-7. PMID: 12529312; PMC: PMC430961