Dataset Information

Multi-omic Pathway and Network Analysis to Identify Biomarkers for Hepatocellular Carcinoma.

ABSTRACT: The threat of Hepatocellular Carcinoma (HCC) is a growing problem, with incidence rates anticipated to near double over the next two decades. The increasing burden makes discovery of novel diagnostic, prognostic, and therapeutic biomarkers distinguishing HCC from underlying cirrhosis a significant focus. In this study, we analyzed tissue and serum samples from 40 HCC cases and 25 patients with liver cirrhosis (CIRR) to better understand the mechanistic differences between HCC and CIRR. Through pathway and network analysis, we are able to take a systems biology approach to conduct multi-omic analysis of transcriptomic, glycoproteomic, and metabolomic data acquired through various platforms. As a result, we are able to identify the FXR/RXR Activation pathway as being represented by molecules spanning multiple molecular compartments in these samples. Specifically, serum metabolites deoxycholate and chenodeoxycholic acid and serum glycoproteins C4A/C4B, KNG1, and HPX are biomarker candidates identified from this analysis that are of interest for future targeted studies. These results demonstrate the integrative power of multi-omic analysis to prioritize clinically and biologically relevant biomarker candidates that can increase understanding of molecular mechanisms driving HCC and make an impact in patient care.

SUBMITTER: Barefoot ME

PROVIDER: S-EPMC6986237 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Multi-omic Pathway and Network Analysis to Identify Biomarkers for Hepatocellular Carcinoma.

Barefoot Megan E ME Varghese Rency S RS Zhou Yuan Y Poto Cristina Di CD Ferrarini Alessia A Ressom Habtom W HW

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference 20190701

The threat of Hepatocellular Carcinoma (HCC) is a growing problem, with incidence rates anticipated to near double over the next two decades. The increasing burden makes discovery of novel diagnostic, prognostic, and therapeutic biomarkers distinguishing HCC from underlying cirrhosis a significant focus. In this study, we analyzed tissue and serum samples from 40 HCC cases and 25 patients with liver cirrhosis (CIRR) to better understand the mechanistic differences between HCC and CIRR. Through p ...[more]

PMID: 31946143

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Project description:To better understand dynamic disease processes, integrated multi-omic methods are needed, yet comparing different types of omic data remains difficult. Integrative solutions benefit experimenters by eliminating potential biases that come with single omic analysis. We have developed the methods needed to explore whether a relationship exists between co-expression network models built from transcriptomic and proteomic data types, and whether this relationship can be used to improve the disease signature discovery process. A naïve, correlation based method is utilized for comparison. Using publicly available infectious disease time series data, we analyzed the related co-expression structure of the transcriptome and proteome in response to SARS-CoV infection in mice. Transcript and peptide expression data was filtered using quality scores and subset by taking the intersection on mapped Entrez IDs. Using this data set, independent co-expression networks were built. The networks were integrated by constructing a bipartite module graph based on module member overlap, module summary correlation, and correlation to phenotypes of interest. Compared to the module level results, the naïve approach is hindered by a lack of correlation across data types, less significant enrichment results, and little functional overlap across data types. Our module graph approach avoids these problems, resulting in an integrated omic signature of disease progression, which allows prioritization across data types for down-stream experiment planning. Integrated modules exhibited related functional enrichments and could suggest novel interactions in response to infection. These disease and platform-independent methods can be used to realize the full potential of multi-omic network signatures. The data (experiment SM001) are publically available through the NIAID Systems Virology (https://www.systemsvirology.org) and PNNL (http://omics.pnl.gov) web portals. Phenotype data is found in the supplementary information. The ProCoNA package is available as part of Bioconductor 2.13.

Dataset Information

Multi-omic Pathway and Network Analysis to Identify Biomarkers for Hepatocellular Carcinoma.

Publications

Multi-omic Pathway and Network Analysis to Identify Biomarkers for Hepatocellular Carcinoma.

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