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CisTopic: cis-regulatory topic modelling on single-cell ATAC-seq data

ABSTRACT: cisTopic: cis-regulatory topic modelling on single-cell ATAC-seq data

PROVIDER: PRJNA471732 | ENA |

REPOSITORIES: ENA

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cisTopic: cis-regulatory topic modelling on single-cell ATAC-seq data

Project description:We present cisTopic, a probabilistic framework to simultaneously discover co-accessible enhancers and stable cell states from sparse single-cell epigenomics data (http://github.com/aertslab/cistopic). On a compendium of single-cell ATAC-seq datasets from differentiating hematopoietic cells, brain, and transcription-factor perturbation dynamics, we demonstrate that topic modelling can be exploited for a robust identification of cell types, enhancers, and relevant transcription factors. cisTopic provides insight into the mechanisms underlying regulatory heterogeneity within cell populations.

2019-02-18 | GSE114557 | GEO

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Human gene regulatory evolution is driven by divergence in cis and trans

Project description:Gene regulation can evolve either by cis-acting local changes to regulatory element DNA sequences or by global changes to the trans-acting regulatory environment; however, the modes favored during recent human evolution are unknown. To date, studies investigating gene regulatory divergence between closely-related species have produced limited estimates on the relative contributions of cis and trans effects on DNA regulatory element activities at a global-scale. By leveraging a comparative ATAC-STARR-seq framework, we identified 10,779 regulatory regions with divergent activity in cis and 10,608 regulatory regions with divergent activity in trans between human and rhesus macaque lymphoblastoid cell lines (LCLs). This revealed substantially more trans effects than predicted and indicates trans-regulatory mechanisms play a larger role in human evolution than previously expected. We also discover that most species-specific regulatory elements (67%) diverge in both cis and trans, suggesting these two mechanisms jointly drive divergent regulatory activity in a single sequence.

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