Enhancer-Promoter Linkage Atlas for the Mouse Islet tissue generated with Enhlink. Insights into Type II Diabetes Mechanisms and Covariate-Specific Regulation

These atlases were generated using single-nucleus ATAC-seq datasets from mouse Islet and Adipose tissues. The aim of the single-cell study on the Islet and Adipose tissues was to understand the genetic-specific mechanisms involved in the development of type II diabetes. The researchers created cell-type specific enhancer-promoter atlases for both tissues, identifying which linkages were specific to the strain, diet, and sex and which intersected with the pcHI-C datasets generated from the same tissues.File descriptionsEach BEDPE file contains genomic links using the 6 first columns to define the enhancer (three first columns) and the promoter (the following three columns). Also, each file refers to a specific cell type written in the file name. The extension pchic refers to the links intersecting the ilset pcHI-C data. The extension unique refers to link unique within a cell type and not found in any of the other cell types.the extension 2ndOrder refers to covariate-specific links with the covariate ID described in one of the columns. Finally, the batch.tsv file describes the covariates associated with each promoter activity.MethodsWe independently processed each cell type of the tissue, considering library ID, sex, diet, and strain as covariates. We applied a p-value cutoff of 0.01 with the secondOrder option and used only 66% of the features, a maximum of 4 features, a depth of 2, and a downsampling size of 15,000 cells to obtain covariate-specific linkages for each tree. We generated a binary cell x promoter sparse matrix by setting 1 for a given gene g and cell c if at least one read from c fell into the promoter regions of g, and used the ATACMatUtils command with the -use_symbol option from the ATACdemultiplex package to create the matrix from the BED file containing the reads and barcode IDs. Finally, we used the enhtools software with the -intersect3 option to intersect the obtained linkage of each cell type with the pcHI-C links of either the Adipose or the Islet tissues.Softwarehttps://gitlab.com/Grouumf/enhlinktoolsCitationhttps://genomebiology.biomedcentral.com/articles/10.1186/s13059-024-03374-9