MOCHA: Advanced statistical modeling of scATAC-seq data enables functional genomic inference in large human disease cohorts
Rachid Zaim, S.; Pebworth, M.-P.; McGrath, I.; Okada, L.; Weiss, M.; Reading, J.; Czartoski, J. L.; Torgerson, T.; McElrath, M. J.; Bumol, T. F.; Skene, P. J.; Li, X.-j.
Show abstract
Single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) has been increasingly used to study gene regulation. However, major analytical gaps limit its utility in studying gene regulatory programs in complex diseases. We developed MOCHA (Model-based single cell Open CHromatin Analysis) with major advances over existing analysis tools, including: 1) improved identification of sample-specific open chromatin, 2) proper handling of technical drop-out with zero-inflated methods, 3) mitigation of false positives in single cell analysis, 4) identification of alternative transcription-starting-site regulation, and 5) transcription factor-gene network construction from longitudinal scATAC-seq data. These advances provide a robust framework to study gene regulatory programs in human disease. We benchmarked MOCHA with four state-of-the-art tools to demonstrate its advances. We also constructed cross-sectional and longitudinal gene regulatory networks, identifying potential mechanisms of COVID-19 response. MOCHA provides researchers with a robust analytical tool for functional genomic inference from scATAC-seq data.
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