title: PATIENT-SPECIFIC DATA FUSION FOR CANCER STRATIFICATION AND PERSONALISED TREATMENT.
abstract: According to Cancer Research UK, cancer is a leading cause of death accounting for more than one in four of all deaths in 2011. The recent advances in experimental technologies in cancer research have resulted in the accumulation of large amounts of patient-specific datasets, which provide complementary information on the same cancer type. We introduce a versatile data fusion (integration) framework that can effectively integrate somatic mutation data, molecular interactions and drug chemical data to address three key challenges in cancer research: stratification of patients into groups having different clinical outcomes, prediction of driver genes whose mutations trigger the onset and development of cancers, and repurposing of drugs treating particular cancer patient groups. Our new framework is based on graph-regularised non-negative matrix tri-factorization, a machine learning technique for co-clustering heterogeneous datasets. We apply our framework on ovarian cancer data to simultaneously cluster patients, genes and drugs by utilising all datasets.We demonstrate superior performance of our method over the state-of-the-art method, Network-based Stratification, in identifying three patient subgroups that have significant differences in survival outcomes and that are in good agreement with other clinical data. Also, we identify potential new driver genes that we obtain by analysing the gene clusters enriched in known drivers of ovarian cancer progression. We validated the top scoring genes identified as new drivers through database search and biomedical literature curation. Finally, we identify potential candidate drugs for repurposing that could be used in treatment of the identified patient subgroups by targeting their mutated gene products. We validated a large percentage of our drug-target predictions by using other databases and through literature curation.
authors.affiliation: Department of Computing, Imperial College London, London, SW7 2AZ, United Kingdom.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gligorijević
authors.forename: Noël
authors.initials: N
authors.lastname: Malod-Dognin
authors.forename: Nataša
authors.initials: N
authors.lastname: Pržulj
mesh_terms: D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D016208:Databases, Factual / Q000706:statistics & numerical data; D058492:Drug Repositioning; D005260:Female; D006801:Humans; D000069550:Machine Learning; D005810:Multigene Family; D009154:Mutation; D009369:Neoplasms / Q000145:classification* / Q000235:genetics / Q000628:therapy*; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000145:classification / Q000188:drug therapy / Q000235:genetics; D057285:Precision Medicine / Q000379:methods / Q000706:statistics & numerical data