Walking on a tissue-specific disease-protein-complex heterogeneous network for the discovery of disease-related protein complexes.
Besides the pinpointing of individual disease-related genes, associating protein complexes to human inherited diseases is also of great importance, because a biological function usually arises from the cooperative behaviour of multiple proteins in a protein complex. Moreover, knowledge about disease-related protein complexes could also enhance the inference of disease genes and pathogenic genetic variants. Here, we have designed a computational systems biology approach to systematically analyse potential relationships between diseases and protein complexes. First, we construct a heterogeneous network which is composed of a disease-disease similarity layer, a tissue-specific protein-protein interaction layer, and a protein complex membership layer. Then, we propose a random walk model on this disease-protein-complex network for identifying protein complexes that are related to a query disease. With a series of leave-one-out cross-validation experiments, we show that our method not only possesses high performance but also demonstrates robustness regarding the parameters and the network structure. We further predict a landscape of associations between human diseases and protein complexes. This landscape can be used to facilitate the inference of disease genes, thereby benefiting studies on pathology of diseases.
MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, FIT 1-107, Beijing 100084, China.
Thibault
T
Jacquemin
MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, FIT 1-107, Beijing 100084, China.
Rui
R
Jiang
D000465:Algorithms; D019295:Computational Biology; D006801:Humans; D008962:Models, Theoretical; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D049490:Systems Biology
D046912:Multiprotein Complexes; D011506:Proteins