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Revealing missing parts of the interactome via link prediction.

ABSTRACT: Protein interaction networks (PINs) are often used to "learn" new biological function from their topology. Since current PINs are noisy, their computational de-noising via link prediction (LP) could improve the learning accuracy. LP uses the existing PIN topology to predict missing and spurious links. Many of existing LP methods rely on shared immediate neighborhoods of the nodes to be linked. As such, they have limitations. Thus, in order to comprehensively study what are the topological properties of nodes in PINs that dictate whether the nodes should be linked, we introduce novel sensitive LP measures that are expected to overcome the limitations of the existing methods. We systematically evaluate the new and existing LP measures by introducing "synthetic" noise into PINs and measuring how accurate the measures are in reconstructing the original PINs. Also, we use the LP measures to de-noise the original PINs, and we measure biological correctness of the de-noised PINs with respect to functional enrichment of the predicted interactions. Our main findings are: 1) LP measures that favor nodes which are both "topologically similar" and have large shared extended neighborhoods are superior; 2) using more network topology often though not always improves LP accuracy; and 3) LP improves biological correctness of the PINs, plus we validate a significant portion of the predicted interactions in independent, external PIN data sources. Ultimately, we are less focused on identifying a superior method but more on showing that LP improves biological correctness of PINs, which is its ultimate goal in computational biology. But we note that our new methods outperform each of the existing ones with respect to at least one evaluation criterion. Alarmingly, we find that the different criteria often disagree in identifying the best method(s), which has important implications for LP communities in any domain, including social networks.

SUBMITTER: Hulovatyy Y

PROVIDER: S-EPMC3940777 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Revealing missing parts of the interactome via link prediction.

Hulovatyy Yuriy Y Solava Ryan W RW Milenković Tijana T

PloS one 20140303 3

Protein interaction networks (PINs) are often used to "learn" new biological function from their topology. Since current PINs are noisy, their computational de-noising via link prediction (LP) could improve the learning accuracy. LP uses the existing PIN topology to predict missing and spurious links. Many of existing LP methods rely on shared immediate neighborhoods of the nodes to be linked. As such, they have limitations. Thus, in order to comprehensively study what are the topological proper ...[more]

PMID: 24594900

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Project description:The origin and deep evolution of retroviruses remain largely unclear. It has been proposed that retroviruses might have originated from a Ty3/Gypsy retrotransposon, but all known Ty3/Gypsy retrotransposons are only distantly related to retroviruses. Retroviruses and some plant Athila/Tat elements (within Ty3/Gypsy retrotransposons) independently evolved a dual RNase H domain and an env/env-like gene. Here, we reported the discovery of a novel lineage of retrotransposons, designated Odin retrotransposons, in the genomes of eight sea anemones (order Actinaria) within the Cnidaria phylum. Odin retrotransposons exhibited unique genome features, encoding a dual RNase H domain (like retroviruses) but no env gene (like most Ty3/Gypsy retrotransposons). Phylogenetic analyses based on reverse transcriptase showed that Odin retrotransposons formed a sister group to lokiretroviruses, and lokiretroviruses and Odin retrotransposons together were sister to canonical retroviruses. Moreover, phylogenetic analyses based on RNase H and integrase also supported the hypothesis that Odin retrotransposons were sisters to lokiretroviruses. Lokiretroviruses and canonical retroviruses did not form a monophyletic group, indicating that lokiretroviruses and canonical retroviruses might represent two distinct virus families. Taken together, the discovery of Odin retrotransposons narrowed down the evolutionary gaps between retrotransposons and canonical retroviruses and lokiretroviruses. IMPORTANCE The origin of retroviruses remains largely unclear. In this study, we discovered a novel retrotransposon lineage, Odin retrotransposons, within the genomes of sea anemones (order Actinaria). In contrast to retroviruses and most retrotransposons, Odin retrotransposons encode a dual RNase H domain but no env gene. Phylogenetic analyses showed that Odin retrotransposons were sisters to lokiretroviruses, and lokiretroviruses and Odin retrotransposons were sisters to retroviruses, establishing an evolutionary framework to decipher the origin of retroviruses (canonical retroviruses and lokiretroviruses). Our results provided insights into the diversity and deep evolution of LTR retrotransposons closely related to retroviruses.

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Revealing missing parts of the interactome via link prediction.

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Revealing missing parts of the interactome via link prediction.

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