DCI: learning causal differences between gene regulatory networks
Name
2020.05.13.093765v1.full.pdf
Description
Submitted version
Size
2 MB
Format
Adobe PDF
Checksum (MD5)
35d68cfcf059a689ca7bb027ea48a5ce
Author(s)
Belyaeva, Anastasiya
Squires, Chandler
Uhler, Caroline
Date Issued
2021
Journal
Bioinformatics
Publisher
Oxford University Press (OUP)
Citation
Belyaeva, Anastasiya, Squires, Chandler and Uhler, Caroline. 2021. "DCI: learning causal differences between gene regulatory networks." Bioinformatics, 37 (18).
Version
Original manuscript
Abstract
Abstract
Summary Designing interventions to control gene regulation necessitates modeling a gene regulatory network by a causal graph. Currently, large-scale gene expression datasets from different conditions, cell types, disease states, and developmental time points are being collected. However, application of classical causal inference algorithms to infer gene regulatory networks based on such data is still challenging, requiring high sample sizes and computational resources. Here, we describe an algorithm that efficiently learns the differences in gene regulatory mechanisms between different conditions. Our difference causal inference (DCI) algorithm infers changes (i.e. edges that appeared, disappeared, or changed weight) between two causal graphs given gene expression data from the two conditions. This algorithm is efficient in its use of samples and computation since it infers the differences between causal graphs directly without estimating each possibly large causal graph separately. We provide a user-friendly Python implementation of DCI and also enable the user to learn the most robust difference causal graph across different tuning parameters via stability selection. Finally, we show how to apply DCI to single-cell RNA-seq data from different conditions and cell states, and we also validate our algorithm by predicting the effects of interventions. Availability and implementation Python package freely available at http://uhlerlab.github.io/causaldag/dci. Supplementary information Supplementary data are available at Bioinformatics online.
Summary Designing interventions to control gene regulation necessitates modeling a gene regulatory network by a causal graph. Currently, large-scale gene expression datasets from different conditions, cell types, disease states, and developmental time points are being collected. However, application of classical causal inference algorithms to infer gene regulatory networks based on such data is still challenging, requiring high sample sizes and computational resources. Here, we describe an algorithm that efficiently learns the differences in gene regulatory mechanisms between different conditions. Our difference causal inference (DCI) algorithm infers changes (i.e. edges that appeared, disappeared, or changed weight) between two causal graphs given gene expression data from the two conditions. This algorithm is efficient in its use of samples and computation since it infers the differences between causal graphs directly without estimating each possibly large causal graph separately. We provide a user-friendly Python implementation of DCI and also enable the user to learn the most robust difference causal graph across different tuning parameters via stability selection. Finally, we show how to apply DCI to single-cell RNA-seq data from different conditions and cell states, and we also validate our algorithm by predicting the effects of interventions. Availability and implementation Python package freely available at http://uhlerlab.github.io/causaldag/dci. Supplementary information Supplementary data are available at Bioinformatics online.
MIT Department
Massachusetts Institute of Technology. Laboratory for Information and Decision Systems
Massachusetts Institute of Technology. Institute for Data, Systems, and Society
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1093/BIOINFORMATICS/BTAB167
