title: Inferring protein modulation from gene expression data using conditional mutual information.
abstract: Systematic, high-throughput dissection of causal post-translational regulatory dependencies, on a genome wide basis, is still one of the great challenges of biology. Due to its complexity, however, only a handful of computational algorithms have been developed for this task. Here we present CINDy (Conditional Inference of Network Dynamics), a novel algorithm for the genome-wide, context specific inference of regulatory dependencies between signaling protein and transcription factor activity, from gene expression data. The algorithm uses a novel adaptive partitioning methodology to accurately estimate the full Condition Mutual Information (CMI) between a transcription factor and its targets, given the expression of a signaling protein. We show that CMI analysis is optimally suited to dissecting post-translational dependencies. Indeed, when tested against a gold standard dataset of experimentally validated protein-protein interactions in signal transduction networks, CINDy significantly outperforms previous methods, both in terms of sensitivity and precision.
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, United States of America; Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, United States of America.
authors.forename: Federico M
authors.initials: FM
authors.lastname: Giorgi
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, United States of America; Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, United States of America.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Lopez
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, United States of America; Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, United States of America.
authors.forename: Jung H
authors.initials: JH
authors.lastname: Woo
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, United States of America; Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, United States of America.
authors.forename: Brygida
authors.initials: B
authors.lastname: Bisikirska
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, United States of America; Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, United States of America; Columbia Genome Center, High Throughput Screening facility, Columbia University, New York, New York, United States of America; Department of Biomedical Informatics, Columbia University, New York, New York, United States of America; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, United States of America; Institute for Cancer Genetics, Columbia University, New York, New York, United States of America; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York, United States of America.
authors.forename: Andrea
authors.initials: A
authors.lastname: Califano
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, United States of America; Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, United States of America.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Bansal
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D049490:Systems Biology
chemical_list: D011506:Proteins; D012333:RNA, Messenger