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However, due to the difficulties of mapping genes to pathways and the limited knowledge about pathway interactions, most previous work focus on identifying individual pathways. In practice, two (or even more) pathways interplay and often cooperatively trigger cancer. In this study, we proposed a new approach called CDPathway to discover cooperative driver pathways. First, CDPathway introduces a driver impact quantification function to quantify the driver weight of each gene. CDPathway assumes that genes with larger weights contribute more to the occurrence of the target disease and identifies them as candidate driver genes. Next, it constructs a heterogeneous network composed of genes, miRNAs and pathways nodes based on the known intra(inter)-relations between them and assigns the quantified driver weights to gene\u2013pathway and gene\u2013miRNA relational edges. To transfer driver impacts of genes to pathway interaction pairs, CDPathway collaboratively factorizes the weighted adjacency matrices of the heterogeneous network to explore the latent relations between genes, miRNAs and pathways. After this, it reconstructs the pathway interaction network and identifies the pathway pairs with maximal interactive and driver weights as cooperative driver pathways. Experimental results on the breast, uterine corpus endometrial carcinoma and ovarian cancer data from The Cancer Genome Atlas show that CDPathway can effectively identify candidate driver genes [area under the receiver operating characteristic curve (AUROC) of $\\geq $0.9] and reconstruct the pathway interaction network (AUROC of&amp;gt;0.9), and it uncovers much more known (potential) driver genes than other competitive methods. In addition, CDPathway identifies 150% more driver pathways and 60% more potential cooperative driver pathways than the competing methods. The code of CDPathway is available at http:\/\/mlda.swu.edu.cn\/codes.php?name=CDPathway.<\/jats:p>","DOI":"10.1093\/bib\/bbz167","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T20:10:15Z","timestamp":1575663015000},"page":"1984-1999","source":"Crossref","is-referenced-by-count":8,"title":["Cooperative driver pathway discovery via fusion of multi-relational data of genes, miRNAs and pathways"],"prefix":"10.1093","volume":"22","author":[{"given":"Jun","family":"Wang","sequence":"first","affiliation":[{"name":"Professor of the School of Software, Shandong University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziying","family":"Yang","sequence":"additional","affiliation":[{"name":"Professor of the School of Software, Shandong University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlotta","family":"Domeniconi","sequence":"additional","affiliation":[{"name":"Department of Computer Science, George Mason 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