17b7d3c37be41135afaf8e91e365e3847af96ca5 lrnassar Mon Jun 22 10:56:56 2026 -0700 Add TAD (topologically associating domains) track set on hg19, hg38, mm10, mm39. refs #21599 New "tads" superTrack collecting published TAD calls, alpha-gated via include tad.ra alpha in each assembly's trackDb.ra. hg38 (all five sources): Dixon 2012 domains, Schmitt 2016 boundaries, McArthur & Capra 2021 boundary stability, ENCODE contact domains (faceted composite over 117 biosamples), and 3D Genome Browser 2.0 domains (faceted composite over 464 datasets). hg19: the three sources with hg19-compatible data (Dixon, Schmitt, McArthur). mm10/mm39 (domains only; the boundary sources have no mouse data): Dixon, ENCODE (faceted, 16 biosamples), and 3D Genome Browser (faceted, 30 datasets); mm39 lifted from mm10, lift noted in the long labels. Faceted composites are organ-colored from a TAD-owned organ_colors.json symlinked into /gbdb/<asm>/bbi/tad/. Build scripts and autoSql are version-controlled under makeDb/scripts/tad/ and symlinked into the per-source build dirs. Provenance and fetch for every dataset are documented in the makedocs (doc/hg38/tad.txt, doc/mm10/tad.txt, doc/mm39/tad.txt, and the hg19 TAD section in doc/hg19.txt). diff --git src/hg/makeDb/trackDb/human/hg38/tads.html src/hg/makeDb/trackDb/human/hg38/tads.html new file mode 100644 index 00000000000..f171171d054 --- /dev/null +++ src/hg/makeDb/trackDb/human/hg38/tads.html @@ -0,0 +1,112 @@ +<h2>Description</h2> +<p> +This track set displays <b>topologically associating domains (TADs)</b> and TAD +<b>boundaries</b> in the human genome, assembled from several published Hi-C studies. +TADs are self-interacting regions of the genome, typically hundreds of kilobases +to about a megabase, and themselves nested, with smaller contact domains contained within +larger top-level TADs. Their boundaries (frequently bound by CTCF and cohesin) insulate +neighboring regions and constrain enhancer-promoter contacts. Disruption of a TAD boundary +can rewire gene regulation and cause disease, and TADs are widely used to nominate candidate +target genes for non-coding variants. +</p> +<p>The set contains five complementary sources:</p> +<ul> + <li><b>Dixon 2012 TADs</b> – the original TAD <em>domains</em> in hESC and IMR90 + cells (lifted from hg18).</li> + <li><b>ENCODE contact domains</b> – uniformly called TAD <em>domains</em> across 117 + ENCODE human biosamples (hg38 only), browsable by a faceted selector (organ, biosample + type, assay). These are finer-resolution (5 kb) sub-TAD contact domains.</li> + <li><b>3D Genome Browser domains</b> – TAD <em>domains</em> across 464 human + Hi-C/Micro-C datasets (normal and cancer, baseline and perturbation), exactly as + called and published by the 3D Genome Browser, browsable by a faceted selector + (organ, cell type, assay, condition, treatment, year, study).</li> + <li><b>Schmitt 2016 boundaries</b> – TAD <em>boundaries</em> across 21 human + tissues and cell lines.</li> + <li><b>TAD boundary stability</b> – how recurrent each boundary is across 37 + cell-type maps (McArthur & Capra 2021).</li> +</ul> + +<h2>How to Use These Tracks</h2> +<p> +The <b>domain</b> tracks (Dixon, ENCODE, 3D Genome Browser) answer "are my variant +and a candidate gene in the same TAD?" and help prioritize target genes at +non-coding GWAS loci. The <b>boundary</b> tracks (Schmitt, stability) answer "does my +structural variant disrupt an insulating boundary?" and help interpret +the regulatory impact of deletions, duplications, and inversions. Because the domain tracks +are nested (ENCODE calls smaller sub-TAD contact domains; Dixon and the 3D Genome Browser +call larger top-level TADs), "which TAD?" is answered at different scales by +different tracks. +</p> + +<h2>Display Conventions and Configuration</h2> +<p> +Each source is shown as a separate track because TAD calls are <b>not directly +comparable across studies</b>: different algorithms (directionality index/HMM, +insulation score, Arrowhead) and resolutions (5–100 kb) produce different calls +of the same underlying biology. <b>Domains</b> are drawn as boxes spanning each +self-interacting region; <b>boundaries</b> are drawn as the short bins that divide +adjacent domains. Because calls are made on binned data, domain edges are uncertain to +roughly the caller's bin size (from a few kilobases for the ENCODE 5 kb calls up to about +±50 kb for the 100 kb stability bins), and the bin width of a boundary feature +reflects this localization precision, not a measured physical width. Domains do not +tile the genome end to end; the gaps between domain boxes are inter-domain or unorganized +regions, not display artifacts. The <b>ENCODE</b> and <b>3D Genome Browser</b> tracks each +contain many biosamples and are browsable with a faceted selector on their track +configuration pages; a small default set is shown and the rest are enabled through the +facets. +</p> + +<h2>Methods</h2> +<p> +See the individual subtrack description pages for full methods, source publications, and +assembly/liftOver details for each dataset. In brief: Dixon domains were called with the +directionality-index HMM at 40 kb; Schmitt boundaries with the insulation-score method at +40 kb; ENCODE contact domains with Arrowhead (Juicer) on the ENCODE uniform Hi-C +pipeline; the 3D Genome Browser domains are that resource's own per-dataset TAD calls +(25 kb) across 464 human datasets, shown verbatim (format normalization only); and the +boundary-stability track counts, per 100 kb window, how many of 37 re-processed cell-type +maps share a boundary (McArthur & Capra 2021). +</p> + +<h2>Data Access</h2> +<p> +The raw data can be explored interactively with the +<a href="hgTables" target="_blank">Table Browser</a> or the +<a href="hgIntegrator" target="_blank">Data Integrator</a>. For programmatic access, the +track can be accessed using the Genome Browser's +<a href="https://genome.ucsc.edu/goldenPath/help/api.html" target="_blank">REST API</a>. +The underlying bigBed files can be downloaded from our +<a href="https://hgdownload.soe.ucsc.edu/gbdb/$db/bbi/tad/" target="_blank">download server</a>. +</p> + +<h2>References</h2> +<p> +Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B. +Topological domains in mammalian genomes identified by analysis of chromatin +interactions. <em>Nature</em>. 2012;485(7398):376-80. +<a href="https://doi.org/10.1038/nature11082" target="_blank">doi:10.1038/nature11082</a> +</p> +<p> +McArthur E, Capra JA. Topologically associating domain boundaries that are stable across +diverse cell types are evolutionarily constrained and enriched for heritability. +<em>Am J Hum Genet</em>. 2021;108(2):269-283. +<a href="https://doi.org/10.1016/j.ajhg.2021.01.001" target="_blank">doi:10.1016/j.ajhg.2021.01.001</a> +</p> +<p> +Rao SS, Huntley MH, Durand NC, Stamenova EK, <em>et al.</em> +A 3D map of the human genome at kilobase resolution reveals principles of chromatin +looping. <em>Cell</em>. 2014;159(7):1665-80. +<a href="https://doi.org/10.1016/j.cell.2014.11.021" target="_blank">doi:10.1016/j.cell.2014.11.021</a> +</p> +<p> +Schmitt AD, Hu M, Jung I, Xu Z, <em>et al.</em> +A Compendium of Chromatin Contact Maps Reveals Spatially Active Regions in the Human +Genome. <em>Cell Rep</em>. 2016;17(8):2042-2059. +<a href="https://doi.org/10.1016/j.celrep.2016.10.061" target="_blank">doi:10.1016/j.celrep.2016.10.061</a> +</p> +<p> +Yu S, Fu Y, Wong JH, Wang J, Zhao H, Zhao J, Yue F. +The 3D Genome Browser 2.0: an enhanced online platform for visualizing and analyzing 3D +genome architecture. <em>Nucleic Acids Res</em>. 2026;54(D1):D48-D54. +<a href="https://doi.org/10.1093/nar/gkaf1109" target="_blank">doi:10.1093/nar/gkaf1109</a> +</p>