Interactive analysis of single-cell epigenomic landscapes with ChromSCape

Abstract

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.

Machine learning for single cell genomics data analysis

“…Several DR methods for single-cell epigenomic data have also been proposed recently, either based on standard PCA models [16, 17], matrix factorization with latent Dirichlet allocation [18], or a VAE [19]. A recent benchmark highlights the importance of preprocessing, in particular how reads are binned into regions of interest and counted, for the success of these methods [20 • ].…”

DeepMAPS: Single-cell biological network inference using heterogeneous graph transformer

“…Considering the complexity of single-cell sequencing data, more and more webservers and dockers have been developed in the past three years [23][24][25][26][27][28][29][30][31][32][33][34][35] (Supplementary Table 6). However, most of these tools only provide minimal and basic functions such as cell clustering and differential gene analysis, and do not support the joint analysis of scMultiomics data, especially lack sufficient support for biological network inference.…”

“…Researchers who lack sufficient computational skills prefer to use webservers or dockers to lessen the programming burden of data analysis, and hence, a code-free and interactive platform for single-cell sequencing data analysis are urgently needed in the public domain. Considering the complexity of single-cell sequencing data, more and more webservers and dockers have been developed in the past three years [23][24][25][26][27][28][29][30][31][32][33][34][35] (Supplementary Table 6). However, most of these tools only provide minimal and basic functions such as cell clustering and differential gene analysis, and do not support the joint analysis of scMultiomics data, especially lack sufficient support for biological network inference.…”

Regulation of Transcription Factor NF-κB in Its Natural Habitat: The Nucleus

“…One reason is that most data have been obtained from large cell populations characterized by heterogeneous NF-κB activation patterns [ 95 ]. Comparative analysis of single-cell epigenomic landscapes, NF-κB activation, and transcriptional responses will thus enable determining the precise temporal order of regulatory events and allow establishing causal relations between the diverse regulatory steps [ 96 , 97 , 98 ]. Causal dependencies between NF-κB and chromatin functions will become better addressable by advanced loss-of-function approaches allowing the rapid (and reversible) inactivation of signaling proteins using conditional degrons [ 99 ] or causing the rapid relocalization of proteins using anchor-away systems or related techniques [ 100 ].…”