基于转录组学数据的癌症转化医学信息学-系统生物学专业论文.docxVIP

PAGE PAGE IV 基于转录组学数据的癌症转化医学信息学 英文摘要 Translational biomedical informatics for cancer transcriptomic data analysis Abstract With the wide application of microarray and next-generation sequencing technology, cancer-related transcriptome data is increasing significantly. How to analyze and integrate these high-throughput information, and translate them from bench to the bedside remains the primary goal for translational medical informatics. There have been numerous laboratory studies that investigate cancer-related gene expression patterns and identify cancer-related molecular markers. However, the marker lists generated by different laboratory are not consistent. This inconsistency not only stems from the variation in experimental platform and analytical methods, more importantly, are caused by the intra-tumor and inter-population heterogeneity of cancer. Here we present specific solutions at three different levels (gene, pathway, population) to address the poor inter-dataset reproducibility, thus improve the robustness and validity of diagnostic markers for cancer. We carried out case studies on two types of cancer transcriptome data: clear cell renal cell carcinoma (ccRCC) and prostate cancer (PCa) to validate that our method is reasonable. We also identified a sensitive and specific diagnostic marker for ccRCC. We first evaluated the consistency between different independent datasets at gene level. We established a unified platform for cancer transcriptome meta-analysis, which was then applied to 5 independent ccRCC microRNA expression datasets for meta-analysis. We compared 5 outlier detection methods and used a novel algorithm, MOST, to account for heterogeneous activation pattern of oncogenes. Secondly, we constructed a predictive model, POMA, to integrate mRNA and microRNA expression profiles. POMA features a reconstructed cancer-specific mRNA-microRNA interaction network, and a scoring algorithm to evaluate the regulatory activity microRNAs. POMA reduces th