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Assembling global maps of cellular function through integrative analysis of physical and genetic networks

Abstract

To take full advantage of high-throughput genetic and physical interaction mapping projects, the raw interactions must first be assembled into models of cell structure and function. PanGIA (for physical and genetic interaction alignment) is a plug-in for the bioinformatics platform Cytoscape, designed to integrate physical and genetic interactions into hierarchical module maps. PanGIA identifies 'modules' as sets of proteins whose physical and genetic interaction data matches that of known protein complexes. Higher-order functional cooperativity and redundancy is identified by enrichment for genetic interactions across modules. This protocol begins with importing interaction networks into Cytoscape, followed by filtering and basic network visualization. Next, PanGIA is used to infer a set of modules and their functional inter-relationships. This module map is visualized in a number of intuitive ways, and modules are tested for functional enrichment and overlap with known complexes. The full protocol can be completed between 10 and 30 min, depending on the size of the data set being analyzed.

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Figure 1: Overview of PanGIA's method for identifying a module map of cellular function from physical and genetic networks.
Figure 2: Outline of the protocol.
Figure 3: The PanGIA console.
Figure 4: PanGIA output.

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Acknowledgements

We gratefully acknowledge S. Bandyophadyay and R. Kelley for their role in the development of the framework used in PanGIA. M. Michaut provided useful feedback on the manuscript. C. Doherty and M. Ashkenazi provided helpful beta testing of the PanGIA plug-in. This study was supported by grants from the National Institute of General Medical Sciences (GM070743), the National Science Foundation (IIS0803937) and Microsoft (Computational Challenges in Genome-wide Association Studies).

Author information

Authors and Affiliations

Authors

Contributions

G.H., R.S. and T.I. conceived and led the project. G.H. coded PanGIA with supporting code from R.S., J.R., K.O., P.-L.W. and M.S. R.S., G.H. and T.I. wrote the paper. All authors have contributed to the design of PanGIA and all have read and approved the paper.

Corresponding author

Correspondence to Trey Ideker.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Data 3

An example Cytoscape node attribute file (see Box 2 for a description of the node attribute file) which assigns a gene to the various physical complexes in which it participates. This file is based on a list of 408 protein complexes in the yeast Saccharomyces cerevisiae taken from the CYC2008 database34,35. [Publisher's Note: This file has been zipped to conform to our Supplemental Information file type policy.] (ZIP 14 kb)

Supplementary Data 1

An example physical interaction network in a tab-delimited format (see Box 1 for a description of the tab-delimited format). The physical interaction network was taken from a recent computational integration of two large datasets generated using tandem affinity purification followed by mass spectrometry (TAP-MS)22. Each physical interaction was assigned a Purification Enrichment score (PE Score), with larger values representing greater confidence in the physical interaction. (TXT 138 kb)

Supplementary Data 2

An example genetic interaction network in a tab-delimited format (see Box 1 for a description of the tab-delimited format). The genetic interaction network was obtained from a large E-MAP screen which measured all possible genetic interactions among 743 genes involved in yeast chromosomal biology3. Each gene pair is assigned an S-score representing both the magnitude and confidence of the genetic interaction. (TXT 332 kb)

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Srivas, R., Hannum, G., Ruscheinski, J. et al. Assembling global maps of cellular function through integrative analysis of physical and genetic networks. Nat Protoc 6, 1308–1323 (2011). https://doi.org/10.1038/nprot.2011.368

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