A large accessory protein interactome is rewired across environments

Abstract
Data availability
Article and author information
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Abstract

To characterize how protein-protein interaction (PPI) networks change, we quantified the relative PPI abundance of 1.6 million protein pairs in the yeast Saccharomyces cerevisiae across 9 growth conditions, with replication, for a total of 44 million measurements. Our multi-condition screen identified 13,764 pairwise PPIs, a 3-fold increase over PPIs identified in one condition. A few 'immutable' PPIs are present across all conditions, while most 'mutable' PPIs are rarely observed. Immutable PPIs aggregate into highly connected 'core' network modules, with most network remodeling occurring within a loosely connected 'accessory' module. Mutable PPIs are less likely to co-express, co-localize, and be explained by simple mass action kinetics, and more likely to contain proteins with intrinsically disordered regions, implying that environment-dependent association and binding is critical to cellular adaptation. Our results show that protein interactomes are larger than previously thought and contain highly dynamic regions that reorganize to drive or respond to cellular changes.

Data availability

Raw barcode sequencing data are available from the NIH Sequence Read Archive as accession PRJNA630095 (https://trace.ncbi.nlm.nih.gov/Traces/study/?acc=SRP259652). Barcode sequences, counts, fitness values, and PPI calls are available in the Supplementary Tables (https://osf.io/jmhrb/). Additional data to make figures are available in Mendeley data (https://data.mendeley.com/datasets/9ygwhk5cs3/2) and Open Science Framework (https://osf.io/7yt59/) as detailed in code repository README files. Analysis scripts are written in R and Python. All code used to analyze data, perform statistical analyses, and generate figures is available at Github (https://github.com/sashaflevy/PPiSeq).

The following data sets were generated

(2020) Protein-protein interaction network rewiring across environments
Mendelay Data, DOI: 10.17632/9ygwhk5cs3.2.

https://data.mendeley.com/datasets/9ygwhk5cs3/2
(2020) Protein-protein interaction network dynamics across environments by DNA barcode sequencing
NIH Sequence Read Archive, accession PRJNA630095.

https://trace.ncbi.nlm.nih.gov/Traces/study/?acc=SRP259652&o=acc_s%3Aa
1. Liu Z
(2020) Protein-protein interaction network rewiring across environments
OSF, jmhrb.

https://osf.io/jmhrb/

Article and author information

Author details

Zhimin Liu

Department of Biochemistry, Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-9333-8101
Darach Miller

Department of Genetics, Stanford University, Palo Alto, United States

Competing interests
No competing interests declared.
Fangfei Li

Department of Applied Mathematics and Statistics, Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, United States

Competing interests
No competing interests declared.
Xianan Liu

Department of Biochemistry, Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, United States

Competing interests
Xianan Liu, S.F.L. and X.L have filed a patent application (WO2017075529A1) on the double barcoding platform used in this manuscript..
Sasha F Levy

Joint Initiative for Metrology in Biology, SLAC National Accelerator Laboratory, Menlo Park, United States [US]

For correspondence
sflevy@stanford.edu

Competing interests
Sasha F Levy, S.F.L. and X.L have filed a patent application (WO2017075529A1) on the double barcoding platform used in this manuscript..

"This ORCID iD identifies the author of this article:" 0000-0002-0923-1636

Funding

National Institutes of Health (R01HG008354)

Sasha F Levy

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.