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.
Highlights
Finding a causal gene is a fundamental problem in genomic medicine
We present a novel application of a causal inference method as a straightforward approach to improve the statistical power in case-control single-cell analysis while adjusting for unwanted confounding effects existing across heterogeneous individuals
We have empirically shown that CoCoA-diff improved the downstream data analysis in extensive simulation experiments
Summary
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
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.