Reconstruction of Gene Regulatory Networks Based on Repairing Sparse Low-Rank Matrices

Young Hwan Chang, Roel Dobbe, Palak Bhushan, Joe Gray, Claire J. Tomlin

Research output: Contribution to journalArticle

Abstract

With the growth of high-throughput proteomic data, in particular time series gene expression data from various perturbations, a general question that has arisen is how to organize inherently heterogenous data into meaningful structures. Since biological systems such as breast cancer tumors respond differently to various treatments, little is known about exactly how these gene regulatory networks (GRNs) operate under different stimuli. Challenges due to the lack of knowledge not only occur in modeling the dynamics of a GRN but also cause bias or uncertainties in identifying parameters or inferring the GRN structure. This paper describes a new algorithm which enables us to estimate bias error due to the effect of perturbations and correctly identify the common graph structure among biased inferred graph structures. To do this, we retrieve common dynamics of the GRN subject to various perturbations. We refer to the task as 'repairing' inspired by 'image repairing' in computer vision. The method can automatically correctly repair the common graph structure across perturbed GRNs, even without precise information about the effect of the perturbations. We evaluate the method on synthetic data sets and demonstrate an application to the DREAM data sets and discuss its implications to experiment design.

Original languageEnglish (US)
Article number7182286
Pages (from-to)767-777
Number of pages11
JournalIEEE/ACM Transactions on Computational Biology and Bioinformatics
Volume13
Issue number4
DOIs
StatePublished - Jul 1 2016

Keywords

  • gene regulatory network
  • repairing
  • System identification

ASJC Scopus subject areas

  • Biotechnology
  • Genetics
  • Applied Mathematics

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