Genetic interactions derived from high-throughput phenotyping of 6589 yeast cell cycle mutants

NPJ Syst Biol Appl. 2020 May 6;6(1):11. doi: 10.1038/s41540-020-0134-z.

Abstract

Over the last 30 years, computational biologists have developed increasingly realistic mathematical models of the regulatory networks controlling the division of eukaryotic cells. These models capture data resulting from two complementary experimental approaches: low-throughput experiments aimed at extensively characterizing the functions of small numbers of genes, and large-scale genetic interaction screens that provide a systems-level perspective on the cell division process. The former is insufficient to capture the interconnectivity of the genetic control network, while the latter is fraught with irreproducibility issues. Here, we describe a hybrid approach in which the 630 genetic interactions between 36 cell-cycle genes are quantitatively estimated by high-throughput phenotyping with an unprecedented number of biological replicates. Using this approach, we identify a subset of high-confidence genetic interactions, which we use to refine a previously published mathematical model of the cell cycle. We also present a quantitative dataset of the growth rate of these mutants under six different media conditions in order to inform future cell cycle models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Cycle / genetics*
  • Cell Division / genetics
  • Computational Biology / methods
  • Epistasis, Genetic / genetics
  • Gene Expression Regulation, Fungal / genetics
  • Gene Regulatory Networks / genetics
  • High-Throughput Screening Assays / methods
  • Models, Theoretical
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics

Substances

  • Saccharomyces cerevisiae Proteins