title: Environmental Interactions and Epistasis Are Revealed in the Proteomic Responses to Complex Stimuli.
abstract: Ultimately, the genotype of a cell and its interaction with the environment determine the cell's biochemical state. While the cell's response to a single stimulus has been studied extensively, a conceptual framework to model the effect of multiple environmental stimuli applied concurrently is not as well developed. In this study, we developed the concepts of environmental interactions and epistasis to explain the responses of the S. cerevisiae proteome to simultaneous environmental stimuli. We hypothesize that, as an abstraction, environmental stimuli can be treated as analogous to genetic elements. This would allow modeling of the effects of multiple stimuli using the concepts and tools developed for studying gene interactions. Mirroring gene interactions, our results show that environmental interactions play a critical role in determining the state of the proteome. We show that individual and complex environmental stimuli behave similarly to genetic elements in regulating the cellular responses to stimuli, including the phenomena of dominance and suppression. Interestingly, we observed that the effect of a stimulus on a protein is dominant over other stimuli if the response to the stimulus involves the protein. Using publicly available transcriptomic data, we find that environmental interactions and epistasis regulate transcriptomic responses as well.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Parimal
authors.initials: P
authors.lastname: Samir
authors.affiliation: Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, Canada.
authors.lastname: Rahul
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: James C
authors.initials: JC
authors.lastname: Slaughter
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America; Department of Chemistry, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Link
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004843:Epistasis, Genetic; D005838:Genotype; D005947:Glucose / Q000494:pharmacology; D005990:Glycerol / Q000494:pharmacology; D013058:Mass Spectrometry; D020543:Proteome / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
chemical_list: D020543:Proteome; D012333:RNA, Messenger; D005947:Glucose; D005990:Glycerol