title: Systematically Prioritizing Functional Differentially Methylated Regions (fDMRs) by Integrating Multi-omics Data in Colorectal Cancer.
abstract: While genome-wide differential DNA methylation regions (DMRs) have been extensively identified, the comprehensive prioritization of their functional importance is still poorly explored. Here, we aggregated multiple data resources rooted in the genome, epigenome and transcriptome to systematically prioritize functional DMRs (fDMRs) in colorectal cancer (CRC). As demonstrated, the top-ranked fDMRs from all of the data resources showed a strong enrichment for known methylated genes. Additionally, we analyzed those top 5% DMR-coupled coding genes using functional enrichment, which resulted in significant disease-related biological functions in contrast to the tail 5% genes. To further confirm the functional importance of the top-ranked fDMRs, we applied chromatin modification alterations of CRC cell lines to characterize their functional regulation. Specifically, we extended the utility of the top-ranked DMR-coupled genes to serve as classification and survival biomarkers, which showed a robust performance across diverse independent data sets. Collectively, our results established an integrative framework to prioritize fDMRs, which could help characterize aberrant DNA methylation-induced potential mechanisms underlying tumorigenesis and uncover epigenome-based biomarkers for clinical diagnosis and prognosis.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Fan
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Zhao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Pang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Guanxiong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Fulong
authors.initials: F
authors.lastname: Yu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Chaohan
authors.initials: C
authors.lastname: Xu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015894:Genome, Human; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D064235:Matrilin Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D029961:Zebrafish Proteins
chemical_list: D014408:Biomarkers, Tumor; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C577548:MATN4 protein, human; D064235:Matrilin Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins