TY - JOUR T1 - Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis A1 - Hess, David C. A1 - Myers, Chad L. A1 - Huttenhower, Curtis A1 - Hibbs, Matthew A. A1 - Hayes, Alicia P. A1 - Paw, Jadine A1 - Clore, John J. A1 - Mendoza, Rosa M. A1 - Luis, Bryan San A1 - Nislow, Corey A1 - Giaever, Guri A1 - Costanzo, Michael A1 - Troyanskaya, Olga G. A1 - Caudy, Amy A. Y1 - 2009/03/20 N2 - Author Summary Mitochondria are the proverbial powerhouses of the cell, running the fundamental biochemical processes that produce energy from nutrients using oxygen. These processes are conserved in all eukaryotes, from humans to model organisms such as baker's yeast. In humans, mitochondrial dysfunction plays a role in a variety of diseases, including diabetes, neuromuscular disorders, and aging. In order to better understand fundamental mitochondrial biology, we studied genes involved in mitochondrial biogenesis in the yeast S. cerevisiae, discovering over 100 proteins with novel roles in this process. These experiments assigned function to 5% of the genes whose function was not known. In order to achieve this rapid rate of discovery, we developed a system incorporating highly quantitative experimental assays and an integrated, iterative process of computational protein function prediction. Beginning from relatively little prior knowledge, we found that computational predictions achieved about 60% accuracy and rapidly guided our laboratory work towards hundreds of promising candidate genes. Thus, in addition to providing a more thorough understanding of mitochondrial biology, this study establishes a framework for successfully integrating computation and experimentation to drive biological discovery. A companion manuscript, published in PLoS Computational Biology (doi:10.1371/journal.pcbi.1000322), discusses observations and conclusions important for the computational community. JF - PLOS Genetics JA - PLOS Genetics VL - 5 IS - 3 UR - https://doi.org/10.1371/journal.pgen.1000407 SP - e1000407 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pgen.1000407 ER -