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. 2023 Sep 5;14:5400. doi: 10.1038/s41467-023-41228-3

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — a Connect T2D downregulated ATAC peaks to downregulated genes from RePACT analyses through multiomic integration (T2D upregulated peak-gene pair in Supplementary Fig. 4). Leftmost panel: heatmap of peaks losing accessibility along T2D trajectory; peak locations (hg19) are on the left of each row. Peaks highlighted in red show intra-donor heterogeneity. Second panel shows the peak-gene connections. Green lines: peaks within 10 kb of the TSS; orange lines: distal peak-gene pairs supported by Hi-C loops. Third panel: the distance of each peak-TSS connection. Rightmost panel: heatmap of T2D downregulated genes. Red-highlighted gene names indicate intra-donor heterogeneous genes. b Enrichment analysis between T2D trajectory genes and T2D-trajectory peaks. Color intensity indicates the odds ratio. P values (two-sided Fisher’s exact test) and the numbers of genes are shown in the squares. c A subnetwork of predicted T2D downregulated genes controlled by HNF1A (Methods). Green lines: peaks within 10 kb of the TSS; orange lines: distal peak-gene pairs supported by Hi-C loops. Maroon: both proximal and distal peaks. d Genome browser snapshot of TTR locus (chr18:29,169,915-29,180,800) which is a putative HNF1A target. e qPCR validation of selected HNF1A targets following HNF1A knock-down. P-values are from two-sided paired t-test. ∗∗∗p < 0.0005, ∗∗p < 0.005, ∗p < 0.05 (three biological replicates each, HNF1A has four biological replicates. Each biological replicate is the average of three technical replicates). Data are presented as mean values +/− SEM.