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Causal network inference from gene transcriptional time-series response to glucocorticoids.

Publication ,  Journal Article
Lu, J; Dumitrascu, B; McDowell, IC; Jo, B; Barrera, A; Hong, LK; Leichter, SM; Reddy, TE; Engelhardt, BE
Published in: PLoS Comput Biol
January 2021

Gene regulatory network inference is essential to uncover complex relationships among gene pathways and inform downstream experiments, ultimately enabling regulatory network re-engineering. Network inference from transcriptional time-series data requires accurate, interpretable, and efficient determination of causal relationships among thousands of genes. Here, we develop Bootstrap Elastic net regression from Time Series (BETS), a statistical framework based on Granger causality for the recovery of a directed gene network from transcriptional time-series data. BETS uses elastic net regression and stability selection from bootstrapped samples to infer causal relationships among genes. BETS is highly parallelized, enabling efficient analysis of large transcriptional data sets. We show competitive accuracy on a community benchmark, the DREAM4 100-gene network inference challenge, where BETS is one of the fastest among methods of similar performance and additionally infers whether causal effects are activating or inhibitory. We apply BETS to transcriptional time-series data of differentially-expressed genes from A549 cells exposed to glucocorticoids over a period of 12 hours. We identify a network of 2768 genes and 31,945 directed edges (FDR ≤ 0.2). We validate inferred causal network edges using two external data sources: Overexpression experiments on the same glucocorticoid system, and genetic variants associated with inferred edges in primary lung tissue in the Genotype-Tissue Expression (GTEx) v6 project. BETS is available as an open source software package at https://github.com/lujonathanh/BETS.

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Published In

PLoS Comput Biol

DOI

EISSN

1553-7358

Publication Date

January 2021

Volume

17

Issue

1

Start / End Page

e1008223

Location

United States

Related Subject Headings

  • Transcriptome
  • Software
  • Models, Statistical
  • Machine Learning
  • Lung
  • Humans
  • Glucocorticoids
  • Computational Biology
  • Bioinformatics
  • Algorithms
 

Citation

APA
Chicago
ICMJE
MLA
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Lu, J., Dumitrascu, B., McDowell, I. C., Jo, B., Barrera, A., Hong, L. K., … Engelhardt, B. E. (2021). Causal network inference from gene transcriptional time-series response to glucocorticoids. PLoS Comput Biol, 17(1), e1008223. https://doi.org/10.1371/journal.pcbi.1008223
Lu, Jonathan, Bianca Dumitrascu, Ian C. McDowell, Brian Jo, Alejandro Barrera, Linda K. Hong, Sarah M. Leichter, Timothy E. Reddy, and Barbara E. Engelhardt. “Causal network inference from gene transcriptional time-series response to glucocorticoids.PLoS Comput Biol 17, no. 1 (January 2021): e1008223. https://doi.org/10.1371/journal.pcbi.1008223.
Lu J, Dumitrascu B, McDowell IC, Jo B, Barrera A, Hong LK, et al. Causal network inference from gene transcriptional time-series response to glucocorticoids. PLoS Comput Biol. 2021 Jan;17(1):e1008223.
Lu, Jonathan, et al. “Causal network inference from gene transcriptional time-series response to glucocorticoids.PLoS Comput Biol, vol. 17, no. 1, Jan. 2021, p. e1008223. Pubmed, doi:10.1371/journal.pcbi.1008223.
Lu J, Dumitrascu B, McDowell IC, Jo B, Barrera A, Hong LK, Leichter SM, Reddy TE, Engelhardt BE. Causal network inference from gene transcriptional time-series response to glucocorticoids. PLoS Comput Biol. 2021 Jan;17(1):e1008223.

Published In

PLoS Comput Biol

DOI

EISSN

1553-7358

Publication Date

January 2021

Volume

17

Issue

1

Start / End Page

e1008223

Location

United States

Related Subject Headings

  • Transcriptome
  • Software
  • Models, Statistical
  • Machine Learning
  • Lung
  • Humans
  • Glucocorticoids
  • Computational Biology
  • Bioinformatics
  • Algorithms