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CoCoA-diff: counterfactual inference for single-cell gene expression analysis Park, Yongjin P.; Kellis, Manolis

Abstract

Finding a causal gene is a fundamental problem in genomic medicine. We present a causal inference framework, CoCoA-diff, that prioritizes disease genes by adjusting confounders without prior knowledge of control variables in single-cell RNA-seq data. We demonstrate that our method substantially improves statistical power in simulations and real-world data analysis of 70k brain cells collected for dissecting Alzheimer’s disease. We identify 215 differentially regulated causal genes in various cell types, including highly relevant genes with a proper cell type context. Genes found in different types enrich distinctive pathways, implicating the importance of cell types in understanding multifaceted disease mechanisms.

Item Metadata

Title
CoCoA-diff: counterfactual inference for single-cell gene expression analysis
Creator
Park, Yongjin P.; Kellis, Manolis
Publisher
BioMed Central
Date Issued
2021-08-17
Description
Finding a causal gene is a fundamental problem in genomic medicine. We present a causal inference framework, CoCoA-diff, that prioritizes disease genes by adjusting confounders without prior knowledge of control variables in single-cell RNA-seq data. We demonstrate that our method substantially improves statistical power in simulations and real-world data analysis of 70k brain cells collected for dissecting Alzheimer’s disease. We identify 215 differentially regulated causal genes in various cell types, including highly relevant genes with a proper cell type context. Genes found in different types enrich distinctive pathways, implicating the importance of cell types in understanding multifaceted disease mechanisms.
Subject
Causal inference; Single-cell RNA-seq; Counterfactual inference; Alzheimer’s disease
Genre
Article
Type
Text
Language
eng
Date Available
2021-08-31
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0401802
URI
http://hdl.handle.net/2429/79533
Affiliation
Medicine, Faculty of; Medicine, Department of; Pathology and Laboratory Medicine, Department of
Citation
Genome Biology. 2021 Aug 17;22(1):228
Publisher DOI
10.1186/s13059-021-02438-4
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s)
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)