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Sensitive and Specific Identification of Protein Complexes in "Perturbed" Protein Interaction Networks From Noisy Pull-Down Data

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Executive Summary

High-throughput mass-spectrometry technology has enabled genome-scale discovery of protein-protein interactions. Yet, computational inference of protein interaction networks and their functional modules from large-scale pull-down data is challenging. Over-expressed or "Sticky" bait is not specific; it generates numerous false positives. This "Curse" of the technique is also its "Blessing" - the sticky bait can pull-down interacting components of other complexes, thus increase sensitivity. Finding optimal trade-offs between coverage and accuracy requires tuning multiple "Knobs," i.e., method parameters. Each selection leads to a putative network, where each network in the set of "Perturbed" networks differs from the others by a few added or removed edges.

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