01bc05ac9a282a6862111502f13601e513d5b60b max Tue Sep 8 06:16:04 2026 -0700 hg38 Fiber-seq: merge the methylation composite into the compendium The accessibility compendium and the separate Methylation composite covered the identical 41 samples, and cartDump.c assigns priority with the data element as the outer loop and the data type as the inner one. So one composite keeps a sample's six subtracks contiguous in the image, where two composites drew an accessibility block followed by a methylation block and comparing the two assays for one sample meant reading past every other sample. Both come off the same molecules in the same experiment, so side by side is the point. fiberSeqMeth is gone and its three data types moved in as cpg, cpgHap and cpgDiff, renamed because "hap" was already taken by the accessibility overlay and a data type name cannot contain an underscore. Subtracks now carry an explicit priority, sample outer and declared data type inner. Without one they fell back to a label sort, so a first visit showed a sample's data types as Peaks, CpG, Acc rather than in the order of the checkbox row above the table. Metadata columns renamed from camelCase to Accession, Sample_class, _Cell_type and _Sample. toTitleStyle() in facetedComposite.js renders an underscore as a space but does not split camelCase, so "sampleClass" appeared verbatim as a column heading. A literal space cannot be used instead: the saved sort order is a space-separated list of column names and the submit code drops any name containing whitespace, which would have made sorting silently fail to persist. Cell type is no longer faceted. A facet value is only offered when it occurs more than once, and 12 of the 14 cell types here are a single sample, so as a facet it drew two checkboxes and left 12 samples unreachable by any cell-type filter. It is a searchable column now, and Sample_class is the only facet until the lab gives us real HPRC metadata that would facet properly. Description page intro rewritten, and it now says the assay measures the same property as DNase-seq and ATAC-seq. refs #36210 diff --git src/hg/makeDb/trackDb/human/hg38/fiberSeq.html src/hg/makeDb/trackDb/human/hg38/fiberSeq.html index 0e8043303cc..b80a5e1dacb 100644 --- src/hg/makeDb/trackDb/human/hg38/fiberSeq.html +++ src/hg/makeDb/trackDb/human/hg38/fiberSeq.html @@ -1,89 +1,92 @@ <h2>Description</h2> <p> -Most of the DNA in a cell is wrapped around nucleosomes or bound by other proteins, and only -the stretches that are left open can be reached by the transcription factors that switch genes -on. Fiber-seq reads out that protein occupancy directly. Permeabilized cells are treated with -a non-specific N6-adenine methyltransferase, which methylates adenines wherever the DNA is -exposed and leaves protected adenines untouched, so each DNA molecule carries a stencil of the -proteins that were sitting on it. The molecules are then sequenced on a PacBio instrument, -which reports the base sequence, the added adenine methylation and the native CpG methylation -from the same read. Because the reads are long enough to carry heterozygous variants, they can -be assigned to one of the two parental chromosomes, giving a separate picture of chromatin for -each haplotype rather than an average of the two. +Fiber-seq maps which parts of each DNA molecule are bound by proteins and which are open. +Permeabilized cells are treated with a non-specific adenine methyltransferase that methylates +only exposed adenines, so nucleosomes and other bound proteins leave an unmethylated footprint +on each molecule. The DNA is then sequenced on a PacBio instrument, which reads the base +sequence, the added adenine methylation and the native CpG methylation from the same molecule. +Because the reads are long enough to span heterozygous variants, they can be phased to a +parental haplotype, giving a chromatin picture for each allele separately rather than an average +of the two. +</p> + +<p> +The accessibility this measures is the same property that DNase-seq and ATAC-seq measure, and +the tracks here can be read much as those are. The difference is that Fiber-seq reports it one +molecule at a time, so a value is a fraction of molecules rather than a pile of cut sites, and +it can be split by haplotype. </p> <p> This collection holds the Fiber-seq data from the Stergachis and Vollger labs for 41 samples, covering common cell lines and lymphoblastoid lines from individuals sequenced by the Human -Pangenome Reference Consortium and the Genome in a Bottle project. It contains three tracks: +Pangenome Reference Consortium and the Genome in a Bottle project. It contains two tracks: </p> <ul> <li><a href="hgTrackUi?g=fiberSeqAcc">Fiber-seq Acc</a> shows percent-accessible chromatin for seven widely used cell lines as a single overlay, so accessibility can be compared across cell types at a glance.</li> - <li><a href="hgTrackUi?g=fiberSeqCompendium">Fiber-seq Compendium</a> gives, for every one of - the 41 samples, the percent-accessible signal, the called FIRE regulatory element peaks - and a per-haplotype accessibility overlay. Samples are selected from a searchable table.</li> - <li><a href="hgTrackUi?g=fiberSeqMeth">Methylation</a> gives per-sample CpG methylation from - the same reads, both combined over the two chromosomes and split by haplotype, together - with the difference between haplotypes at several significance thresholds.</li> + <li><a href="hgTrackUi?g=fiberSeqCompendium">Fiber-seq Compendium</a> holds everything, for + every one of the 41 samples: the percent-accessible signal, the called FIRE regulatory + element peaks, CpG methylation, and per-haplotype versions of the accessibility and the + methylation. Samples are selected from a searchable table.</li> </ul> <p> Related data can be found in the <a href="hgTrackUi?g=dnaMethylation">DNA Methylation</a> collection, which holds methylation measured by other assays. </p> <h2>Display Conventions</h2> <p> -Each of the three tracks has its own display conventions and its own color scheme; see the -individual track description pages linked above. Signal tracks are scaled 0 to 100 percent -throughout, so a bar height means the same thing in every track and every sample. +Both tracks have their own display conventions and color schemes; see the individual track +description pages linked above. Signal tracks are scaled 0 to 100 percent throughout, so a bar +height means the same thing in every track and every sample. </p> <h2>Methods</h2> <p> The data were generated and processed by the Stergachis and Vollger labs. Details of the assay, the machine learning model that calls regulatory elements from single molecules, and the methylation calling are given on the individual track description pages. </p> <h2>Data Access</h2> <p> The individual track description pages linked above explain how to download the underlying bigWig and bigBed files and how to query them from scripts. </p> <h2>Credits</h2> <p> Thanks to Mitchell Vollger, Andrew Stergachis and Shane Neph at the University of Washington and the University of Utah for generating this data, for packaging it for the browser and for their help in arranging the tracks. </p> <h2>References</h2> <p> Vollger MR, Swanson EG, Neph SJ, Ranchalis J, Munson KM, Ho CH, Cheng YHH, Sedeño-Cortés AE, Fondrie WE, Bohaczuk SC <em>et al</em>. <a href="https://www.ncbi.nlm.nih.gov/pubmed/40501892" target="_blank"> A haplotype-resolved view of human gene regulation</a>. <em>bioRxiv</em>. 2025 Jun 2;. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/40501892" target="_blank">40501892</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157683/" target="_blank">PMC12157683</a> </p> <p> Stergachis AB, Debo BM, Haugen E, Churchman LS, Stamatoyannopoulos JA. <a href="https://www.ncbi.nlm.nih.gov/pubmed/32587015" target="_blank"> Single-molecule regulatory architectures captured by chromatin fiber sequencing</a>. <em>Science</em>. 2020 Jun 26;368(6498):1449-1454. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/32587015" target="_blank">32587015</a> </p>