Network-based prediction of protein interactions

By István A. Kovács, Katja Luck, Kerstin Spirohn, Yang Wang, Carl Pollis, Sadie Schlabach, Wenting Bian, Dae-Kyum Kim, Nishka Kishore, Tong Hao and 3 more. Nature Communications, 2018

435 citations recorded by the source corpus.

Despite exceptional experimental efforts to map out the human interactome, the continued data incompleteness limits our ability to understand the molecular roots of human disease. Computational tools offer a promising alternative, helping identify biologically significant, yet unmapped protein-protein interactions (PPIs). While link prediction methods connect proteins on the basis of biological or network-based similarity, interacting proteins are not necessarily similar and similar proteins do not necessarily interact. Here, we offer structural and evolutionary evidence that proteins interact not if they are similar to each other, but if one of them is similar to the other’s partners. This approach, that mathematically relies on network paths of length three (L3), significantly outperforms all existing link prediction methods. Given its high accuracy, we show that L3 can offer mechanistic insights into disease mechanisms and can complement future experimental efforts to complete the human interactome. Computational protein-protein interaction (PPI) prediction has the potential to complement experimental efforts to map interactomes. Here, the authors show that proteins tend to interact if one is similar to the other’s partners and that PPI prediction based on this principle is highly accurate.

Subfields: Computational Theory and Mathematics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0ded7a6f60e160f6d6baed1dddc39371797f8fef

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Citations in the corpus

Network-based prediction of drug combinations (2019, positive): “In addition, advanced network-based link prediction methods rooted in biological principles 37 can help to develop a combined, quantitative score for each predicted drug combination.”
A reference map of the human binary protein interactome (2020, background): “8h, Supplementary Table 26), suggesting that OTUD6A participates in the apoptosis pathway but is not an inducer of cell death.”