Semi-supervised network inference using simulated gene expression dynamics

Phan Nguyen*, Rosemary Braun

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Motivation Inferring the structure of gene regulatory networks from high-Throughput datasets remains an important and unsolved problem. Current methods are hampered by problems such as noise, low sample size, and incomplete characterizations of regulatory dynamics, leading to networks with missing and anomalous links. Integration of prior network information (e.g. from pathway databases) has the potential to improve reconstructions. Results We developed a semi-supervised network reconstruction algorithm that enables the synthesis of information from partially known networks with time course gene expression data. We adapted partial least square-variable importance in projection (VIP) for time course data and used reference networks to simulate expression data from which null distributions of VIP scores are generated and used to estimate edge probabilities for input expression data. By using simulated dynamics to generate reference distributions, this approach incorporates previously known regulatory relationships and links the network to the dynamics to form a semi-supervised approach that discovers novel and anomalous connections. We applied this approach to data from a sleep deprivation study with KEGG pathways treated as prior networks, as well as to synthetic data from several DREAM challenges, and find that it is able to recover many of the true edges and identify errors in these networks, suggesting its ability to derive posterior networks that accurately reflect gene expression dynamics. Availability and implementation R code is available at https://github.com/pn51/postPLSR. Contact rbraun@northwestern.edu Supplementary informationSupplementary dataare available at Bioinformatics online.

Original languageEnglish (US)
Pages (from-to)1148-1156
Number of pages9
JournalBioinformatics
Volume34
Issue number7
DOIs
StatePublished - Apr 1 2018

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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