Time-lagged Ordered Lasso for network inference

Phan Nguyen, Rosemary Braun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Accurate gene regulatory networks can be used to explain the emergence of different phenotypes, disease mechanisms, and other biological functions. Many methods have been proposed to infer networks from gene expression data but have been hampered by problems such as low sample size, inaccurate constraints, and incomplete characterizations of regulatory dynamics. Since expression regulation is dynamic, time-course data can be used to infer causality, but these datasets tend to be short or sparsely sampled. In addition, temporal methods typically assume that the expression of a gene at a time point depends on the expression of other genes at only the immediately preceding time point, while other methods include additional time points without any constraints to account for their temporal distance. These limitations can contribute to inaccurate networks with many missing and anomalous links. Results: We adapted the time-lagged Ordered Lasso, a regularized regression method with temporal monotonicity constraints, for de novo reconstruction. We also developed a semi-supervised method that embeds prior network information into the Ordered Lasso to discover novel regulatory dependencies in existing pathways. R code is available at https://github.com/pn51/laggedOrderedLassoNetwork. Conclusions: We evaluated these approaches on simulated data for a repressilator, time-course data from past DREAM challenges, and a HeLa cell cycle dataset to show that they can produce accurate networks subject to the dynamics and assumptions of the time-lagged Ordered Lasso regression.

Original languageEnglish (US)
Article number545
JournalBMC bioinformatics
Volume19
Issue number1
DOIs
StatePublished - Dec 29 2018

Keywords

  • Gene network reconstruction
  • Gene regulation
  • Lasso
  • Network inference
  • Penalized regression
  • Regularization
  • Time course data

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

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