RESUMO
MOTIVATION: Accurate classification of patients into molecular subgroups is critical for the development of effective therapeutics and for deciphering what drives these subgroups to cancer. The availability of multiomics data catalogs for large cohorts of cancer patients provides multiple views into the molecular biology of the tumors with unprecedented resolution. RESULTS: We develop Pathway-based MultiOmic Graph Kernel clustering (PAMOGK) that integrates multiomics patient data with existing biological knowledge on pathways. We develop a novel graph kernel that evaluates patient similarities based on a single molecular alteration type in the context of a pathway. To corroborate multiple views of patients evaluated by hundreds of pathways and molecular alteration combinations, we use multiview kernel clustering. Applying PAMOGK to kidney renal clear cell carcinoma (KIRC) patients results in four clusters with significantly different survival times (P-value =1.24e-11). When we compare PAMOGK to eight other state-of-the-art multiomics clustering methods, PAMOGK consistently outperforms these in terms of its ability to partition KIRC patients into groups with different survival distributions. The discovered patient subgroups also differ with respect to other clinical parameters such as tumor stage and grade, and primary tumor and metastasis tumor spreads. The pathways identified as important are highly relevant to KIRC. AVAILABILITY AND IMPLEMENTATION: github.com/tastanlab/pamogk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Algoritmos , Neoplasias , Análise por Conglomerados , Humanos , Neoplasias/genéticaRESUMO
MOTIVATION: The use of genome data for diagnosis and treatment is becoming increasingly common. Researchers need access to as many genomes as possible to interpret the patient genome, to obtain some statistical patterns and to reveal disease-gene relationships. The sensitive information contained in the genome data and the high risk of re-identification increase the privacy and security concerns associated with sharing such data. In this article, we present an approach to identify disease-associated variants and genes while ensuring patient privacy. The proposed method uses secure multi-party computation to find disease-causing mutations under specific inheritance models without sacrificing the privacy of individuals. It discloses only variants or genes obtained as a result of the analysis. Thus, the vast majority of patient data can be kept private. RESULTS: Our prototype implementation performs analyses on thousands of genomic data in milliseconds, and the runtime scales logarithmically with the number of patients. We present the first inheritance model (recessive, dominant and compound heterozygous) based privacy-preserving analyses of genomic data to find disease-causing mutations. Furthermore, we re-implement the privacy-preserving methods (MAX, SETDIFF and INTERSECTION) proposed in a previous study. Our MAX, SETDIFF and INTERSECTION implementations are 2.5, 1122 and 341 times faster than the corresponding operations of the state-of-the-art protocol, respectively. AVAILABILITY AND IMPLEMENTATION: https://gitlab.com/DIFUTURE/privacy-preserving-genomic-diagnosis. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.