Normalization value norm value raw median controls

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Normalization: Value norm = ( Value raw Median controls ) / STD patients
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Scientific Questions By combining the clinical and heterogeneous high- throughput data, can we discover Ovarian cancer subtypes whose outcomes are different? Whether we can find active regulatory pathways of the subtypes which could explain their different prognosis?
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Selecting the Ovarian Cancer Hazard Factors To investigate which features are related to the prognosis of ovarian cancer, we first used Cox proportional hazard model to perform the regression analysis between each feature and the patients’ survival time. In total we selected 4,526 features as hazard factors (P < 0.05), including 1,651 genes’ expression changes, 455 genes’ promoter DNA methylation changes, 140 miRNAs’ expression changes, and the CNAs of 2,191 genes and 89 miRNAs.
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De novo discovery of ovarian cancer subtypes by adaptive clustering
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Signatures of the 7 subtypes of Ovarian Cancer These signatures were identified using Wilcoxon rank-sum test.
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Enriched terms of subtype 2-specific up-regulated genes These terms, such as cell adhesion, TGF-beta binding, angiogenesis and positive regulation of cell proliferation, are related to tumorigenesis and metastasis.
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Comparing the survival curves between subtype 2 and stage IV patients The 5-year survival rate of subtype 2 was even worse than that of tumor stage IV.
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The cancer knowledge base Pathways in cancer Telomere maintenance Inflammatory response MAPK signaling pathway VEGF signaling pathway Glycolysis / Gluconeogenesis mTOR signaling pathway Wnt signaling pathway T cell receptor signaling pathway ErbB signaling pathway ECM-receptor interaction B cell receptor signaling pathway Jak-STAT signaling pathway Adherens junction Natural killer cell mediated cytotoxicity Cytokine-cytokine receptor interaction Focal adhesion Cell cycle p53 signaling pathway PPAR signaling pathway Base excision repair TGF-beta signaling pathway Mismatch repair Apoptosis Nucleotide excision repair Hanahan & Weinberg 2011 The hallmarks of cancer Used to filter out signature genes that are not drivers of cancer.
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The interaction network of signature genes
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THANKS Q & A?
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  • Fall '19
  • DNA, ovarian cancer, Bayesian network

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