Journal Article

Interactive analysis of single-cell epigenomic landscapes with ChromSCape

Deloger, Marc, Kirchmeier, Pia, Servant, Nicolas, Vallot, Céline, Marsolier, Justine, Prompsy, Pacôme

2020

Overview

Chromatin modifications orchestrate the dynamic regulation of gene expression during development and in disease. Bulk approaches have characterized the wide repertoire of histone modifications across cell types, detailing their role in shaping cell identity. However, these population-based methods do not capture cell-to-cell heterogeneity of chromatin landscapes, limiting our appreciation of the role of chromatin in dynamic biological processes. Recent technological developments enable the mapping of histone marks at single-cell resolution, opening up perspectives to characterize the heterogeneity of chromatin marks in complex biological systems over time. Yet, existing tools used to analyze bulk histone modifications profiles are not fit for the low coverage and sparsity of single-cell epigenomic datasets. Here, we present ChromSCape, a user-friendly interactive Shiny/R application distributed as a Bioconductor package, that processes single-cell epigenomic data to assist the biological interpretation of chromatin landscapes within cell populations. ChromSCape analyses the distribution of repressive and active histone modifications as well as chromatin accessibility landscapes from single-cell datasets. Using ChromSCape, we deconvolve chromatin landscapes within the tumor micro-environment, identifying distinct H3K27me3 landscapes associated with cell identity and breast tumor subtype. Bulk approaches fail to capture the cell-to-cell heterogeneity of chromatin landscapes, while single-cell approaches provide low coverage datasets. Here, the authors present ChromSCape, a user-friendly interactive application that processes single-cell epigenomic data to assist the biological interpretation of chromatin landscapes within cell populations, as demonstrated in the context of cancer.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45/15 / 45/62 / 631/114 / 631/114/2164 / 631/208/200 / 631/337/100/2285 / 631/67/1347 / Animals / Bioinformatics / Biological activity / Breast cancer / Breast Neoplasms - genetics / Chromatin / Chromatin - genetics / Chromatin - metabolism / Chromatin Immunoprecipitation / Computational Biology - methods / Computer Science / Datasets / Epigenomics - methods / Female / Gene expression / Heterogeneity / Histones / Histones - genetics / Histones - metabolism / Humanities and Social Sciences / Humans / Mice, Nude / multidisciplinary / Populations / Protein Processing, Post-Translational / Science / Science (multidisciplinary) / Single-Cell Analysis - methods / Software / Tumor Microenvironment / Tumors / User-Computer Interface / Workflow / Xenograft Model Antitumor Assays