Connecting genotype to phenotype through integrated biochemical and statistical models
Institute for Systems Biology
April 17, 2014
Foege N130A, Wallace H. Coulter Seminar Room
To harness the power of genomics, it is essential to link genotype to phenotype through the construction of quantitative systems models. I will discuss approaches for the creation of such quantitative models that can simulate a variety of cellular functions. I will focus particularly on automated methods for integrating metabolic and gene regulatory networks such as our approach, Probabilistic Regulation of Metabolism (PROM). PROM is notable in that it represents the successful integration of a top-down reconstructed, statistically inferred regulatory network with a bottom-up reconstructed, biochemically detailed metabolic network, bridging two important classes of systems biology models that are rarely combined quantitatively. Additionally, I will discuss our new strategy — Gene Expression and Metabolism Integrated for Network Inference (GEMINI) — that is the first method that curates the inference of regulatory interactions from high throughput data using metabolic networks. This novel approach provides multiple layers of biological context to the problem of regulation. I will also present an approach for automated reconstruction of metabolic networks using genomics evidence, and show how evolutionary relationships and networks can be used synergistically to enhance both network reconstruction as well as gene annotation. Finally, I will describe our latest work simulating single-cell growth rates from molecular counts of proteins across cell populations, with associated experimental validation.
Nathan Price is Associate Director of the Institute for Systems Biology in Seattle, WA. Dr. Price is the recipient of numerous awards including the Howard Temin Pathway to Independence Award in Cancer Research from the National Institutes of Health, a National Science Foundation CAREER award, a Young Investigator Award from the Roy J. Carver Charitable Trust, and was named as one of the inaugural “Tomorrow’s Principal Investigators” by Genome Technology and, most recently, as a Camille-Dreyfus Teacher-Scholar. Dr. Price served on the National Academies-Institute of Medicine committee to set best practice guidelines to identify Omics-based Tests for Predicting Patient Outcomes in Clinical Trials. Dr. Price has served on the scientific advisory boards of a number of companies including TetraVitae Bioscience, Global Genomics Group, and Trelys. He serves on the editorial boards of Science Translational Medicine, BMC Systems Biology, Industrial Biotechnology, and Biotechnology Journal, and was Deputy Editor of PLOS Computational Biology from 2011-2014. He has served for several years on the Board of Directors and Scientific Advisory Board of the P4 Medicine Institute. Dr. Price is also Co-PI of ISB’s 100K Wellness study, which is a pioneering effort to predict and prevent disease before it happens.