Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions

<p>Abstract</p> <p>Background</p> <p>High-throughput methods for detecting protein-protein interactions enable us to obtain large interaction networks, and also allow us to computationally identify the associations of proteins as protein complexes. Although there are methods to extract protein complexes as sets of proteins from interaction networks, the extracted complexes may include false positives because they do not account for the structural limitations of the proteins and thus do not check that the proteins in the extracted complex can simultaneously bind to each other. In addition, there have been few searches for deeper insights into the protein complexes, such as of the topology of the protein-protein interactions or into the domain-domain interactions that mediate the protein interactions.</p> <p>Results</p> <p>Here, we introduce a combinatorial approach for prediction of protein complexes focusing not only on determining member proteins in complexes but also on the DDI/PPI organization of the complexes. Our method analyzes complex candidates predicted by the existing methods. It searches for optimal combinations of domain-domain interactions in the candidates based on an assumption that the proteins in a candidate can form a true protein complex if each of the domains is used by a single protein interaction. This optimization problem was mathematically formulated and solved using binary integer linear programming. By using publicly available sets of yeast protein-protein interactions and domain-domain interactions, we succeeded in extracting protein complex candidates with an accuracy that is twice the average accuracy of the existing methods, MCL, MCODE, or clustering coefficient. Although the configuring parameters for each algorithm resulted in slightly improved precisions, our method always showed better precision for most values of the parameters.</p> <p>Conclusions</p> <p>Our combinatorial approach can provide better accuracy for prediction of protein complexes and also enables to identify both direct PPIs and DDIs that mediate them in complexes.</p

キョウショウ シンリン ニ セイソク スル タイリクモモンガ Pteromys volans ニ ヨル スバショ センタク ニ オケル キセツテキ オヨビ セイテキ チガイ ノ ヒョウカ

われわれは巣資源が限られた狭小森林において,タイリクモモンガ(Pteromys volans)の巣場所を選択の行動を理解するため,7個体によって利用された巣と利用可能な巣の巣間距離を比較した。雄と雌の距離は有意に異ならなかった。これは,すべての個体が狭小森林内にある巣だけを利用し,近隣のどの巣も利用しなかったためかもしれない。タイリクモモンガが利用可能な巣と比べて有意に近い距離にある巣を非積雪期に利用したため,われわれの結果は夏～秋での巣場所選択性を示した。一方,積雪期には,利用された巣間の距離と利用可能な巣間の距離に有意な差はなかった。これは,タイリクモモンガが非積雪期に近くの利用可能な巣を選択する一方で,積雪期には数少ない良質の巣を利用するために遠くまで移動したためであると示唆された。特に,タイリクモモンガの保全にあたっては,冬季の巣を含む複数の巣の存在が森林内に不可欠である。We compared distances among used nests and available nests of seven Siberian flying squirrels (Pteromys volans) to understand their nest selection behavior in a small woodlot with limited nest resources. Distances of male and female did not significantly differ. This may be due to the fact that all the P. volans depended on nests only within the small woodlot and did not use any nests in nearby forests. Our results showed selectivity of nest sites in summer to autumn, because they used significantly short distance nests in snow-free season compared with available nests. Whereas, in snowy season, there was no significant difference between the mean distance among selected nest sites and that among available nest sites. It was suggested that the flying squirrel selects available nests nearby in the snow-free season, whereas in the snowy season they travel longer distances to use the rarer better nests in the small habitat. For conservation of the Siberian flying squirrel, multiple nests including the winter nest are necessary in a woodlot

Uchida_et_al_2019_BEHECO

Data of Uchida et al. (2019) Behavioral Ecolog