ATAC-seq signal intensity states for identifying cCREs This composite tracks display the discretized signal intensity levels for ATAC-seq generated by analyzing normalized ATAC-seq signals across cell types using IDEAS in the signal intensity state (IS) mode (Xiang et al. 2024). In this way, the continuous ATAC-seq signal is converted to four discrete states of signal strength, which were then processed to generate peak calls across cell types (see Figure on the track settings page for the super track). This method helps counteract excessive expansion of peak calls when combining them. The resulting peak calls correspond to regions of high accessibility for DNA in chromatin, which is a hallmark of regulatory regions. Hence, they are considered candidate CREs. The cCREs can be displayed using the companion track "cCREs".
In "dense" mode, the display shows the assignment of all genomic intervals to a discrete chromatin accessibility state. Intervals with no ATAC-seq signal significantly above background were assigned to state 0 and were colored white. The violet colored segments represent three states (1-3) with progressively higher signals indicated by deeper shades of violet. In "pack" or "full" mode, the genomic intervals are labeled with the state number.
The track names (short name and the end of the long name) give an abbreviation for the blood cell type and the biosamples from the Blueprint Consortium (replicates are from different donors) or the file id after downloading and processing other published data (100xxx). The cell types are HSC = hematopoietic stem cell, MPP = multipotent progenitor cell, LMPP = lymphoid-myeloid primed progenitor cell, CMP = common myeloid progenitor, MEP = megakaryocyte erythrocyte progenitor, GMP = granulocyte monocyte progenitor, CLP = common lymphoid progenitor, CD34_E = erythroblasts generated by in vitro differentiation of CD34+ HSCs, ERY = erythroblast, MK = megakaryocyte, EOS = eosinophil, MONp = primary monocyte, MONc = classical monocyte, NEU = neutrophil, B = B cell, NK = natural killer cell, T_CD4 = CD4+ T cell, T_CD8 = CD8+ T cell, HUDEP = immortalized human umbilical cord blood—derived erythroid progenitor cell lines expressing fetal globin genes (HUDEP1) or adult globin genes (HUDEP2), K562 = a human cancer cell line with some features of early megakaryocytic and erythroid cells. AVE is a track with state assignments based on the average signal for each epigenetic feature across cell types.
The use of IDEAS in the IS mode for peak calling on chromatin accessibility data was described in Xiang et al. 2021 and Xiang et al. 2024.
The data normalization and peak calls using IDEAS in the IS mode and generation of the joint metaclusters were done by Guanjue Xiang. The data downloads, re-mapping and processing, generation of the tracks displayed, and development of the track hub were done by Belinda Giardine.
Xiang G, Keller CA, Heuston E, Giardine BM, An L, Wixom AQ, Miller A, Cockburn A, Sauria MEG, Weaver K, Lichtenberg J, Göttgens B, Li Q, Bodine D, Mahony S, Taylor J, Blobel GA, Weiss MJ, Cheng Y, Yue F, Hughes J, Higgs DR, Zhang Y, Hardison RC. An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis. Genome Res. 2020 Mar;30(3):472-484. PMID: 32132109; PMCID: PMC7111515.
Xiang G, Keller CA, Giardine B, An L, Li Q, Zhang Y, Hardison RC. S3norm: simultaneous normalization of sequencing depth and signal-to-noise ratio in epigenomic data. Nucleic Acids Res. 2020 May 7;48(8):e43. doi:10.1093/nar/gkaa105. PMID: 32086521; PMCID: PMC7192629.
Xiang G, Giardine BM, Mahony S, Zhang Y, Hardison RC. S3V2-IDEAS: a package for normalizing, denoising and integrating epigenomic datasets across different cell types. Bioinformatics. 2021 Sep 29;37(18):3011-3013. doi:10.1093/bioinformatics/btab148. PMID: 33681991; PMCID: PMC8479670.
Xiang G, He X, Giardine BM, Isaac KJ, Taylor DJ, McCoy RC, Jansen C, Keller CA, Wixom AQ, Cockburn A, Miller A, Qi Q, He Y, Li Y, Lichtenberg J, Heuston EF, Anderson SM, Luan J, Vermunt MW, Yue F, Sauria MEG, Schatz MC, Taylor J, Göttgens B, Hughes JR, Higgs DR, Weiss MJ, Cheng Y, Blobel GA, Bodine DM, Zhang Y, Li Q, Mahony S, Hardison RC. Interspecies regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes. Genome Res. 2024 Aug 20;34(7):1089-1105. PMID: 38951027; PMCID: PMC11368181.
These data are available for use without restrictions.
Ross Hardison rch8@psu.edu