Cancer is an ideal target for personal genomics-based medicine that uses high-throughput genome assays such as DNA sequencing, RNA sequencing, and expression analysis (collectively called omics); however, researchers and physicians are overwhelmed by the quantities of big data from these assays and cannot interpret this information accurately without specialized tools. To address this problem, I have created software methods and tools called OCCAM (OmiC data Cancer Analytic Model) and DIPSC (Differential Pathway Signature Correlation) for automatically extracting knowledge from this data and turning it into an actionable knowledge base called the activitome. An activitome signature measures a mutation's effect on the cellular molecular pathway. As well, activitome signatures can also be computed for clinical phenotypes. By comparing the vectors of activitome signatures of different mutations and clinical outcomes, intrinsic relationships between these events may be uncovered. OCCAM identifies activitome signatures that can be used to guide the development and application of therapies. DIPSC overcomes the confounding problem of correlating multiple activitome signatures from the same set of samples. In addition, to support the collection of this big data, I have developed MedBook, a federated distributed social network designed for a medical research and decision support system. OCCAM and DIPSC are two of the many apps that will operate inside of MedBook. MedBook extends the Galaxy system with a signature database, an end-user oriented application platform, a rich data medical knowledge-publishing model, and the Biomedical Evidence Graph (BMEG). The goal of MedBook is to improve the outcomes by learning from every patient.
|Advisor:||Haussler, David, Stuart, Josh|
|Commitee:||Benz, Christopher, Collisson, Eric|
|School:||University of California, Santa Cruz|
|Department:||Biomolecular Engineering and Bioinformatics|
|School Location:||United States -- California|
|Source:||DAI-B 74/11(E), Dissertation Abstracts International|
|Subjects:||Biomedical engineering, Medicine, Bioinformatics|
|Keywords:||Big data, Cancer, Genomics, Pathways, Targeted therapy, Translational medicine|
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