simultaneous genome-wide inference of physical, genetic, regulatory, and functional pathway components同时全基因组物理推理,遗传、监管和功能通路组件.pdfVIP

Simultaneous Genome-Wide Inference of Physical, Genetic, Regulatory, and Functional Pathway Components 1,2 3 4 1,2 Christopher Y. Park , David C. Hess , Curtis Huttenhower *, Olga G. Troyanskaya * 1 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America, 2 Department of Computer Science, Princeton University, Princeton, New Jersey, United States of America, 3 Department of Biology, Santa Clara University, Santa Clara, California, United States of America, 4 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America Abstract Biomolecular pathways are built from diverse types of pairwise interactions, ranging from physical protein-protein interactions and modifications to indirect regulatory relationships. One goal of systems biology is to bridge three aspects of this complexity: the growing body of high-throughput data assaying these interactions; the specific interactions in which individual genes participate; and the genome-wide patterns of interactions in a system of interest. Here, we describe methodology for simultaneously predicting specific types of biomolecular interactions using high-throughput genomic data. This results in a comprehensive compendium of whole-genome networks for yeast, derived from ,3,500 experimental conditions and describing 30 interaction types, which range from general (e.g. physical or regulatory) to specific (e.g. phosphorylation or transcriptional regulation). We used these networks to investigate molecular pathways in carbon metabolism and cellular transport, proposing a novel co