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      MDICC: novel method for multi-omics data integration and cancer subtype identification

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          Abstract

          Each type of cancer usually has several subtypes with distinct clinical implications, and therefore the discovery of cancer subtypes is an important and urgent task in disease diagnosis and therapy. Using single-omics data to predict cancer subtypes is difficult because genomes are dysregulated and complicated by multiple molecular mechanisms, and therefore linking cancer genomes to cancer phenotypes is not an easy task. Using multi-omics data to effectively predict cancer subtypes is an area of much interest; however, integrating multi-omics data is challenging. Here, we propose a novel method of multi-omics data integration for clustering to identify cancer subtypes (MDICC) that integrates new affinity matrix and network fusion methods. Our experimental results show the effectiveness and generalization of the proposed MDICC model in identifying cancer subtypes, and its performance was better than those of currently available state-of-the-art clustering methods. Furthermore, the survival analysis demonstrates that MDICC delivered comparable or even better results than many typical integrative methods.

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          Most cited references38

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          Is Open Access

          Comprehensive Molecular Characterization of Human Colon and Rectal Cancer

          Summary To characterize somatic alterations in colorectal carcinoma (CRC), we conducted genome-scale analysis of 276 samples, analyzing exome sequence, DNA copy number, promoter methylation, mRNA and microRNA expression. A subset (97) underwent low-depth-of-coverage whole-genome sequencing. 16% of CRC have hypermutation, three quarters of which have the expected high microsatellite instability (MSI), usually with hypermethylation and MLH1 silencing, but one quarter has somatic mismatch repair gene mutations. Excluding hypermutated cancers, colon and rectum cancers have remarkably similar patterns of genomic alteration. Twenty-four genes are significantly mutated. In addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9, and FAM123B/WTX. Recurrent copy number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive CRC and important role for MYC-directed transcriptional activation and repression.
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            The somatic genomic landscape of glioblastoma.

            We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer. Copyright © 2013 Elsevier Inc. All rights reserved.
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              The genomic landscapes of human breast and colorectal cancers.

              Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
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                Author and article information

                Journal
                Briefings in Bioinformatics
                Oxford University Press (OUP)
                1467-5463
                1477-4054
                May 2022
                May 13 2022
                May 2022
                May 13 2022
                April 18 2022
                : 23
                : 3
                Affiliations
                [1 ]College of Mathematics and Statistics, Shenzhen University, 518000, China
                [2 ]College of Life and Health Sciences, Northeastern University, Shenyang, 110169, China
                [3 ]Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, 610056, China
                Article
                10.1093/bib/bbac132
                35437603
                1bae7348-a900-42e9-8c74-edf34b951c41
                © 2022

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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