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Tan, S. J.

Publications and source records attributed to Tan, S. J..

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Compendiums of Cancer Transcriptome for Machine Learning Applications

BackgroundThere exist massive transcriptome profiles in the form of microarray, enabling reuse. The challenge is that they are processed with diverse platforms and preprocessing tools, requiring considerable time and informatics expertise for cross-dataset or cross-cancer analyses. If there exists a single, integrated data source consisting of thousands of samples, similar to TCGA, data-reuse will be facilitated for discovery, analysis, and validation of biomarker-based clinical strategy.\n\nFindingsWe present 11 merged microarray-acquired datasets (MMDs) of major cancer types, curating 8,386 patient-derived tumor and tumor-free samples from 95 GEO datasets. Highly concordant MMD-derived patterns of genome-wide differential gene expression were observed with matching TCGA cohorts. Using machine learning algorithms, we show that clinical models trained from all MMDs, except breast MMD, can be directly applied to RNA-seq-acquired TCGA data with an average accuracy of 0.96 in classifying cancer. Machine learning optimized MMD further aids to reveal immune landscape of human cancers critically needed in disease management and clinical interventions.\n\nConclusionsTo facilitate large-scale meta-analysis, we generated a newly curated, unified, large-scale MMD across 11 cancer types. Besides TCGA, this single data source may serve as an excellent training or test set to apply, develop, and refine machine learning algorithms that can be tapped to better define genomic landscape of human cancers.

bioinformatics

Cross-platform meta-analysis reveals common matrisome variation associated with tumor genotypes and immunophenotypes in human cancers

BackgroundRecent sequencing efforts unveil genomic landscapes of the tumor microenvironment. Yet, little is known about the extent to which matrisome pattern is conserved in progressive tumors across diverse cancer types, and thus its clinical impact remains largely unexplored.\n\nFindingsUsing a newly generated, unified data resource, we conducted cross-platform assessment of a measure of altered extra-cellular matrix (ECM) composition and remodeling associated with tumor progression, termed as the matrisome index (TMI). Parallel analyses with TCGA in over 30,000 patient-derived biopsies revealed that TMI is closely associated with mutational load, tumor histopathology, and predictive of patient outcomes. We found an enrichment of specific tumor-infiltrating immune cell populations, signatures predictive of immunotherapy resistance, and several immune checkpoints in tumors with high TMI, suggesting potential role of ECM interaction with immunophenotyes and tumor immune escape mechanisms. Both epithelial cancer cells and carcinoma-associated fibroblasts are potential cellular contributors of such deregulated matrisome.\n\nConclusionsDespite wide spectrum of genetic heterogeneity and dynamic nature, matrisome abnormalities are integral to disease progression. Our resource of a curated compendium of 8,386 genome-wide profiles, molecular and clinical associations, and matrisome-tumor genotype-immunophenotype relationships identify potentially actionable immune targets that may guide personalized immunotherapy.

genomics