Dataset Information

MOTA: Network-Based Multi-Omic Data Integration for Biomarker Discovery.

ABSTRACT: The recent advancement of omic technologies provides researchers with the possibility to search for disease-associated biomarkers at the system level. The integrative analysis of data from a large number of molecules involved at various layers of the biological system offers a great opportunity to rank disease biomarker candidates. In this paper, we propose MOTA, a network-based method that uses data acquired at multiple layers to rank candidate disease biomarkers. The networks constructed by MOTA allow users to investigate the biological significance of the top-ranked biomarker candidates. We evaluated the performance of MOTA in ranking disease-associated molecules from three sets of multi-omic data representing three cohorts of hepatocellular carcinoma (HCC) cases and controls with liver cirrhosis. The results demonstrate that MOTA allows the identification of more top-ranked metabolite biomarker candidates that are shared by two different cohorts compared to traditional statistical methods. Moreover, the mRNA candidates top-ranked by MOTA comprise more cancer driver genes compared to those ranked by traditional differential expression methods.

SUBMITTER: Fan Z

PROVIDER: S-EPMC7241240 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

MOTA: Network-Based Multi-Omic Data Integration for Biomarker Discovery.

Fan Ziling Z Zhou Yuan Y Ressom Habtom W HW

Metabolites 20200408 4

The recent advancement of omic technologies provides researchers with the possibility to search for disease-associated biomarkers at the system level. The integrative analysis of data from a large number of molecules involved at various layers of the biological system offers a great opportunity to rank disease biomarker candidates. In this paper, we propose MOTA, a network-based method that uses data acquired at multiple layers to rank candidate disease biomarkers. The networks constructed by MO ...[more]

PMID: 32276350

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Project description:Differential expression (DE) analysis is commonly used to identify biomarker candidates that have significant changes in their expression levels between distinct biological groups. One drawback of DE analysis is that it only considers the changes on single biomolecule level. Recently, differential network (DN) analysis has become popular due to its capability to measure the changes on biomolecular pair level. In DN analysis, network is typically built based on correlation and biomarker candidates are selected by investigating the network topology. However, correlation tends to generate over-complicated networks and the selection of biomarker candidates purely based on network topology ignores the changes on single biomolecule level. In this paper, we propose a novel approach, INDEED, that builds sparse differential network based on partial correlation and integrates DE and DN analyses for biomarker discovery. We applied this approach on real proteomic and glycomic data generated by liquid chromatography coupled with mass spectrometry for hepatocellular carcinoma (HCC) biomarker discovery study. For each omic data, we used one dataset to select biomarker candidates, built a disease classifier and evaluated the performance of the classifier on an independent dataset. The biomarker candidates, selected by INDEED, were more reproducible across independent datasets, and led to a higher classification accuracy in predicting HCC cases and cirrhotic controls compared with those selected by separate DE and DN analyses. INDEED also identified some candidates previously reported to be relevant to HCC, such as intercellular adhesion molecule 2 (ICAM2) and c4b-binding protein alpha chain (C4BPA), which were missed by both DE and DN analyses. In addition, we applied INDEED for survival time prediction based on transcriptomic data acquired by analysis of samples from breast cancer patients. We selected biomarker candidates and built a regression model for survival time prediction based on a gene expression dataset and patients' survival records. We evaluated the performance of the regression model on an independent dataset. Compared with the biomarker candidates selected by DE and DN analyses, those selected through INDEED led to more accurate survival time prediction.

Project description:BackgroundType 2 diabetes (T2D) onset is a complex, organized biological process with multilevel regulation, and its physiopathological mechanisms are yet to be elucidated. This study aims to find out the key drivers and pathways involved in the pathogenesis of T2D through multi-omics analysis.MethodsThe datasets used in the experiments comprise three groups: (1) genomic (2) transcriptomic, and (3) epigenomic categories. Then, a series of bioinformatics technologies including Marker set enrichment analysis (MSEA), weighted key driver analysis (wKDA) was performed to identify key drivers. The hub genes were further verified by the Receiver Operator Characteristic (ROC) Curve analysis, proteomic analysis, and Real-time quantitative polymerase chain reaction (RT-qPCR). The multi-omics network was applied to the Pharmomics pipeline in Mergeomics to identify drug candidates for T2D treatment. Then, we used the drug-gene interaction network to conduct network pharmacological analysis. Besides, molecular docking was performed using AutoDock/Vina, a computational docking program.ResultsModule-gene interaction network was constructed using MSEA, which revealed a significant enrichment of immune-related activities and glucose metabolism. Top 10 key drivers (PSMB9, COL1A1, COL4A1, HLA-DQB1, COL3A1, IRF7, COL5A1, CD74, HLA-DQA1, and HLA-DRB1) were selected by wKDA analysis. Among these, COL5A1, IRF7, CD74, and HLA-DRB1 were verified to have the capability to diagnose T2D, and expression levels of PSMB9 and CD74 had significantly higher in T2D patients. We further predict the co-expression network and transcription factor (TF) binding specificity of the key driver. Besides, based on module interaction networks and key driver networks, 17 compounds are considered to possess T2D-control potential, such as sunitinib.ConclusionsWe identified signature genes, biomolecular processes, and pathways using multi-omics networks. Moreover, our computational network analysis revealed potential novel strategies for pharmacologic interventions of T2D.

Dataset Information

MOTA: Network-Based Multi-Omic Data Integration for Biomarker Discovery.

Publications

MOTA: Network-Based Multi-Omic Data Integration for Biomarker Discovery.

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