7a820a27de93e79180f99ae0e149585b5d1bb126 mspeir Tue Dec 23 16:02:10 2025 -0800 adding better species coloring description to rest of conservation tracks, refs #27217 diff --git src/hg/makeDb/trackDb/cat/felCat4/cons6way.html src/hg/makeDb/trackDb/cat/felCat4/cons6way.html index 0e8a3fbd753..92459756140 100644 --- src/hg/makeDb/trackDb/cat/felCat4/cons6way.html +++ src/hg/makeDb/trackDb/cat/felCat4/cons6way.html @@ -1,454 +1,456 @@ <H2>Description</H2> <P> This track shows multiple alignments of 6 mammal species and measurements of evolutionary conservation using two methods (<em>phastCons</em> and <em>phyloP</em>) from the <A HREF="http://compgen.cshl.edu/phast/" target=_BLANK> PHAST package</A>, for all 13 species. The multiple alignments were generated using multiz and other tools in the UCSC/<A HREF="http://www.bx.psu.edu/miller_lab/" TARGET=_blank>Penn State Bioinformatics</A> comparative genomics alignment pipeline. Conserved elements identified by phastCons are also displayed in this track. </P> <P> 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). </P> <P> 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. </P> <P> 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, placental mammals, and glires). Thus, in regions in which only glires appear in the alignment, all three sets of scores will be the same, but in regions in which additional species are available, the mammalian and/or vertebrate scores may differ from the glire scores. The alternative plots help to identify sequences that are under different evolutionary pressures in, say, glires and non-glires, or mammals and non-mammals. </P> The multiple alignments were generated using multiz and other tools in the UCSC/<A HREF="http://www.bx.psu.edu/miller_lab/" TARGET=_blank>Penn State Bioinformatics</A> comparative genomics alignment pipeline. The conservation measurements were created using the phastCons package from <A HREF="https://siepellab.labsites.cshl.edu/" TARGET=_blank> Adam Siepel</A> at Cold Spring Harbor Laboratory. </P> <P> UCSC has repeatmasked and aligned the low-coverage genome assemblies, and provides the sequence for download; however, we do not construct genome browsers for them. Missing sequence in the low-coverage assemblies is highlighted in the track display by regions of yellow when zoomed out and Ns displayed at base level (see <EM>Gap Annotation</EM>, below). </P> <P> <BLOCKQUOTE><TABLE BORDER=1 CELLPADDING=4 BORDERCOLOR="#aaaaaa"> <TR ALIGN=left><TH>Organism</TH><TH>Species</TH><TH>Release date</TH><TH>UCSC version</TH><TH>alignment type</TH></TR> <TR ALIGN=left><TD>Cat</TD><TD>Felis catus</TD><TD> Dec. 2008</TD><TD><A HREF="../cgi-bin/hgGateway?db=felCat4" TARGET=_blank>felCat4</A></TD><TD>reference species</TD></TR> <TR ALIGN=left><TD>Dog</TD><TD>Canis lupus familiaris</TD><TD> May 2005</TD><TD><A HREF="../cgi-bin/hgGateway?db=canFam2" TARGET=_blank>canFam2</A></TD><TD>Syntenic Net</TD></TR> <TR ALIGN=left><TD>Panda</TD><TD>Ailuropoda melanoleuca</TD><TD> Dec 2009</TD><TD><A HREF="../cgi-bin/hgGateway?db=ailMel1" TARGET=_blank>ailMel1</A></TD><TD>Reciprocal Best</TD></TR> <TR ALIGN=left><TD>Human</TD><TD>Homo sapiens</TD><TD> Feb. 2009</TD><TD> <A HREF="../cgi-bin/hgGateway?db=hg19" TARGET=_blank>hg19/GRCh37</A></TD><TD>Syntenic Net</TD></TR> <TR ALIGN=left><TD>Mouse</TD><TD>Mus musculus</TD><TD> July 2007</TD><TD><A HREF="../cgi-bin/hgGateway?db=mm9" TARGET=_blank>mm9</A></TD><TD>Syntenic Net</TD></TR> <TR ALIGN=left><TD>Opossum</TD><TD>Monodelphis domestica</TD><TD> Oct. 2006</TD><TD><A HREF="../cgi-bin/hgGateway?db=monDom5" TARGET=_blank>monDom5</A></TD><TD>Syntenic Net</TD></TR> </TABLE><BR> <B>Table 1.</B> <EM>Genome assemblies included in the 6-way Conservation track.</EM> </BLOCKQUOTE></P> Downloads for data in this track are available: <UL> <LI> <A HREF="http://hgdownload.soe.ucsc.edu/goldenPath/felCat4/multiz6way/">Multiz alignments</A> (MAF format), and phylogenetic trees <LI> <A HREF="http://hgdownload.soe.ucsc.edu/goldenPath/felCat4/phyloP6way/">PhyloP conservation</A> (WIG format) <LI> <A HREF="http://hgdownload.soe.ucsc.edu/goldenPath/felCat4/phastCons6way/">PhastCons conservation</A> (WIG format) </UL> <H2>Display Conventions and Configuration</H2> <P> The track configuration options allow the user to display either the vertebrate or placental mammal conservation scores, or both simultaneously. In full and pack display modes, conservation scores are displayed as a <EM>wiggle track</EM> (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 <A HREF="../goldenPath/help/hgWiggleTrackHelp.html" TARGET=_blank>Graph configuration help</A> link for an explanation of the configuration options.</P> <P> Pairwise alignments of each species to the $organism 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. </P> <P> Checkboxes on the track configuration page allow selection of the species to include in the pairwise display. +The names of selected species are colored according to their clade, +alternating between blue and green. Note that excluding species from the pairwise display does not alter the the conservation score display.</P> <P> 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.</P> <H3>Gap Annotation</H3> <P> The <EM>Display chains between alignments</EM> 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: <UL> <LI><B>Single line:</B> No bases in the aligned species. Possibly due to a lineage-specific insertion between the aligned blocks in the $organism genome or a lineage-specific deletion between the aligned blocks in the aligning species. <LI><B>Double line:</B> 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. <LI><B>Pale yellow coloring:</B> 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. </UL></P> <H3>Genomic Breaks</H3> <P> Discontinuities in the genomic context (chromosome, scaffold or region) of the aligned DNA in the aligning species are shown as follows: <UL> <LI> <B>Vertical blue bar:</B> Represents a discontinuity that persists indefinitely on either side, <em>e.g.</em> 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. <LI> <B>Green square brackets:</B> 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 $organism genome that aligns to a paralogous copy somewhere else in the aligned species, or other similar occurrence. </UL></P> <H3>Base Level</H3> <P> 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 $organism sequence at those alignment positions relative to the longest non-$organism 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 "+".</P> <P> 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: <UL> <LI> <B>No codon translation:</B> The gene annotation is not used; the bases are displayed without translation. <LI> <B>Use default species reading frames for translation:</B> The annotations from the genome displayed in the <EM>Default species to establish reading frame</EM> pull-down menu are used to translate all the aligned species present in the alignment. <LI> <B>Use reading frames for species if available, otherwise no translation:</B> Codon translation is performed only for those species where the region is annotated as protein coding. <LI><B>Use reading frames for species if available, otherwise use default species:</B> 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. </UL></P> <P> Codon translation uses the following gene tracks as the basis for translation, depending on the species chosen (<B>Table 2</B>). Species listed in the row labeled "None" do not have species-specific reading frames for gene translation. <BLOCKQUOTE><TABLE BORDER=1 CELLPADDING=4 BORDERCOLOR="#aaaaaa"> <TR ALIGN=left><TD><B>Gene Track</B></TD><TD><B>Species</B></TD></TR> <TR ALIGN=left><TD>N-SCAN Genes</TD><TD>Cat</TD></TR> <TR ALIGN=left><TD>Ensembl Genes</TD><TD>Dog, Opossum</TD></TR> <TR ALIGN=left><TD>Known Genes</TD><TD>human, mouse</TD></TR> </TABLE><BR> <B>Table 2.</B> <EM>Gene tracks used for codon translation.</EM> </BLOCKQUOTE></P> <H2>Methods</H2> <P> Pairwise alignments with the $organism 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.</P> <P> 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 <A HREF="http://hgdownload.soe.ucsc.edu/goldenPath/felCat4/multiz6way" TARGET=_blank>bulk download</A>. 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.</P> <h3> Phylogenetic Tree Model</h3> <P> Both <em>phastCons</em> and <em>phyloP</em> 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 <A HREF="http://hgdownload.soe.ucsc.edu/goldenPath/felCat4/phastCons6way/all.mod" TARGET=_blank>vertebrate tree model</A> for this track was generated using the <em>phyloFit</em> program from the PHAST package (REV model, EM algorithm, medium precision) using multiple alignments of 4-fold degenerate sites extracted from the 6way alignment (msa_view). The 4d sites were derived from the RefSeq (coding) gene set, filtered to select single-coverage long transcripts. </P> <h3> PhastCons Conservation </h3> <P> 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 <EM>et al</EM>. 2005.</P> <P> The phastCons parameters used were: --expected-length=45, --target-coverage=0.3 and --rho=0.3. </P> <h3> PhyloP Conservation </h3> <P> The phyloP program supports several different methods for computing p-values of conservation or acceleration, for individual nucleotides or larger elements (<a href="http://compgen.cshl.edu/phast/" target="_blank"> http://compgen.cshl.edu/phast/</a>). 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). </P> <h3> Conserved Elements </h3> <P> 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". </P> <H2>Credits</H2> <P> This track was created using the following programs: <UL> <LI> Alignment tools: lastz (formerly blastz) and multiz by Minmei Hou, Scott Schwartz and Webb Miller of the <A HREF="http://www.bx.psu.edu/miller_lab/" TARGET=_blank>Penn State Bioinformatics Group</A> <LI> Chaining and Netting: axtChain, chainNet by Jim Kent at UCSC <LI> Conservation scoring: phastCons, phyloP, phyloFit, tree_doctor, msa_view and other programs in PHAST by <A HREF="https://siepellab.labsites.cshl.edu/" TARGET=_blank>Adam Siepel</A> at Cold Spring Harbor Laboratory (original development done at the Haussler lab at UCSC). <LI> MAF Annotation tools: mafAddIRows by Brian Raney, UCSC; mafAddQRows by Richard Burhans, Penn State; genePredToMafFrames by Mark Diekhans, UCSC <LI> Tree image generator: phyloPng by Galt Barber, UCSC <LI> Conservation track display: Kate Rosenbloom, Hiram Clawson (wiggle display), and Brian Raney (gap annotation and codon framing) at UCSC </UL> </P> <P>The phylogenetic tree is based on Murphy <EM>et al</EM>. (2001) and general consensus in the vertebrate phylogeny community as of March 2007. </P> <H2>References</H2> <H3>Phylo-HMMs, phastCons, and phyloP:</H3> <p> Felsenstein J, Churchill GA. <a href="https://academic.oup.com/mbe/article/13/1/93/1055515" target="_blank">A Hidden Markov Model approach to variation among sites in rate of evolution</a>. <em>Mol Biol Evol</em>. 1996 Jan;13(1):93-104. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/8583911" target="_blank">8583911</a> </p> <p> Pollard KS, Hubisz MJ, Rosenbloom KR, Siepel A. <a href="https://genome.cshlp.org/content/20/1/110.long" target="_blank"> Detection of nonneutral substitution rates on mammalian phylogenies</a>. <em>Genome Res</em>. 2010 Jan;20(1):110-21. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/19858363" target="_blank">19858363</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798823/" target="_blank">PMC2798823</a> </p> <p> Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S, <em>et al.</em> <a href="https://genome.cshlp.org/content/15/8/1034" target="_blank">Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes</a>. <em>Genome Res</em>. 2005 Aug;15(8):1034-50. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/16024819" target="_blank">16024819</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182216/" target="_blank">PMC1182216</a> </p> <p> Siepel A, Haussler D. <a href="http://compgen.cshl.edu/~acs/phylohmm.pdf" target="_blank">Phylogenetic Hidden Markov Models</a>. In: Nielsen R, editor. Statistical Methods in Molecular Evolution. New York: Springer; 2005. pp. 325-351. </p> <p> Yang Z. <a href="https://www.genetics.org/content/139/2/993" target="_blank">A space-time process model for the evolution of DNA sequences</a>. <em>Genetics</em>. 1995 Feb;139(2):993-1005. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/7713447" target="_blank">7713447</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1206396/" target="_blank">PMC1206396</a> </p> <H3>Chain/Net:</H3> <p> Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. <a href="https://www.pnas.org/content/100/20/11484" target="_blank">Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes</a>. <em>Proc Natl Acad Sci U S A</em>. 2003 Sep 30;100(20):11484-9. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/14500911" target="_blank">14500911</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC208784/" target="_blank">PMC208784</a> </p> <H3>Multiz:</H3> <p> Blanchette M, Kent WJ, Riemer C, Elnitski L, Smit AF, Roskin KM, Baertsch R, Rosenbloom K, Clawson H, Green ED, <em>et al.</em> <a href="https://genome.cshlp.org/content/14/4/708.abstract" target="_blank">Aligning multiple genomic sequences with the threaded blockset aligner</a>. <em>Genome Res</em>. 2004 Apr;14(4):708-15. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/15060014" target="_blank">15060014</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC383317/" target="_blank">PMC383317</a> </p> <H3>Lastz (formerly Blastz):</H3> <p> Chiaromonte F, Yap VB, Miller W. <a href="http://psb.stanford.edu/psb-online/proceedings/psb02/chiaromonte.pdf" target="_blank">Scoring pairwise genomic sequence alignments</a>. <em>Pac Symp Biocomput</em>. 2002:115-26. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/11928468" target="_blank">11928468</a> </p> <p> Harris RS. <a href="http://www.bx.psu.edu/~rsharris/rsharris_phd_thesis_2007.pdf" target="_blank">Improved pairwise alignment of genomic DNA</a>. <em>Ph.D. Thesis</em>. Pennsylvania State University, USA. 2007. </p> <p> Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. <a href="https://genome.cshlp.org/content/13/1/103.abstract" target="_blank">Human-mouse alignments with BLASTZ</a>. <em>Genome Res</em>. 2003 Jan;13(1):103-7. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/12529312" target="_blank">12529312</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC430961/" target="_blank">PMC430961</a> </p> <H3>Phylogenetic Tree:</H3> <p> Murphy WJ, Eizirik E, O'Brien SJ, Madsen O, Scally M, Douady CJ, Teeling E, Ryder OA, Stanhope MJ, de Jong WW, Springer MS. <a href="https://science.sciencemag.org/content/294/5550/2348" target="_blank">Resolution of the early placental mammal radiation using Bayesian phylogenetics</a>. <em>Science</em>. 2001 Dec 14;294(5550):2348-51. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/11743200" target="_blank">11743200</a> </p>