title: Reconstruction of Gene Regulatory Networks based on Repairing Sparse Low-rank Matrices.
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.
authors.affiliation: Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720 USA.
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720 USA.
authors.forename: Roel
authors.initials: R
authors.lastname: Dobbe
authors.affiliation: Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720 USA.
authors.forename: Palak
authors.initials: P
authors.lastname: Bhushan
authors.affiliation: Department of Biomedical Engineering and the Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Joe W
authors.initials: JW
authors.lastname: Gray
authors.affiliation: Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720 USA; Faculty Scientist, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 USA.
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Tomlin
mesh_terms: D000465:Algorithms; D001943:Breast Neoplasms / Q000235:genetics; D005260:Female; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D049490:Systems Biology / Q000379:methods*