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Empowering biologists with multi-omics data: colorectal cancer as a paradigm.

ABSTRACT: Recent completion of the global proteomic characterization of The Cancer Genome Atlas (TCGA) colorectal cancer (CRC) cohort resulted in the first tumor dataset with complete molecular measurements at DNA, RNA and protein levels. Using CRC as a paradigm, we describe the application of the NetGestalt framework to provide easy access and interpretation of multi-omics data.The NetGestalt CRC portal includes genomic, epigenomic, transcriptomic, proteomic and clinical data for the TCGA CRC cohort, data from other CRC tumor cohorts and cell lines, and existing knowledge on pathways and networks, giving a total of more than 17 million data points. The portal provides features for data query, upload, visualization and integration. These features can be flexibly combined to serve various needs of the users, maximizing the synergy among omics data, human visualization and quantitative analysis. Using three case studies, we demonstrate that the portal not only provides user-friendly data query and visualization but also enables efficient data integration within a single omics data type, across multiple omics data types, and over biological networks.The NetGestalt CRC portal can be freely accessed at http://www.netgestalt.org.bing.zhang@vanderbilt.eduSupplementary data are available at Bioinformatics online.

SUBMITTER: Zhu J

PROVIDER: S-EPMC4410657 | biostudies-other | 2015 May

REPOSITORIES: biostudies-other

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Empowering biologists with multi-omics data: colorectal cancer as a paradigm.

Zhu Jing J Shi Zhiao Z Wang Jing J Zhang Bing B

Bioinformatics (Oxford, England) 20141218 9

<h4>Motivation</h4>Recent completion of the global proteomic characterization of The Cancer Genome Atlas (TCGA) colorectal cancer (CRC) cohort resulted in the first tumor dataset with complete molecular measurements at DNA, RNA and protein levels. Using CRC as a paradigm, we describe the application of the NetGestalt framework to provide easy access and interpretation of multi-omics data.<h4>Results</h4>The NetGestalt CRC portal includes genomic, epigenomic, transcriptomic, proteomic and clinica ...[more]

PMID: 25527095

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Project description:Background: The potential biological processes and laws of the biological components in malignant tumors can be understood more systematically and comprehensively through multi-omics analysis. This study elaborately explored the role of lipid metabolism in the prognosis of colorectal cancer (CRC) from the metabonomics and transcriptomics. Methods: We performed K-means unsupervised clustering algorithm and t test to identify the differential lipid metabolites determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) in the serum of 236 CRC patients of the First Hospital of Jilin University (JLUFH). Cox regression analysis was used to identify prognosis-associated lipid metabolites and to construct multi-lipid-metabolite prognostic signature. The composite nomogram composed of independent prognostic factors was utilized to individually predict the outcome of CRC patients. Glycerophospholipid metabolism was the most significant enrichment pathway for lipid metabolites in CRC, whose related hub genes (GMRHGs) were distinguished by gene set variation analysis (GSVA) and weighted gene co-expression network analysis (WGCNA). Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis were utilized to develop the prognostic signature. Results: Six-lipid-metabolite and five-GMRHG prognostic signatures were developed, indicating favorable survival stratification effects on CRC patients. Using the independent prognostic factors as variables, we established a composite nomogram to individually evaluate the prognosis of CRC patients. The AUCs of one-, three-, and five-year ROC curves were 0.815, 0.815, and 0.805, respectively, showing auspicious prognostic accuracy. Furthermore, we explored the potential relationship between tumor microenvironment (TME) and immune infiltration. Moreover, the mutational frequency of TP53 in the high-risk group was significantly higher than that in the low-risk group (p < 0.001), while in the coordinate mutational status of TP53, the overall survival of CRC patients in the high-risk group was significantly lower than that in low-risk group with statistical differences. Conclusion: We identified the significance of lipid metabolism for the prognosis of CRC from the aspects of metabonomics and transcriptomics, which can provide a novel perspective for promoting individualized treatment and revealing the potential molecular biological characteristics of CRC. The composite nomogram including a six-lipid-metabolite prognostic signature is a promising predictor of the prognosis of CRC patients.

Dataset Information

Empowering biologists with multi-omics data: colorectal cancer as a paradigm.

Publications

Empowering biologists with multi-omics data: colorectal cancer as a paradigm.

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