J Am Med Inform Assoc - Extracting coordinated patterns of DNA methylation and gene expression in ovarian cancer.

Tópicos

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Resumo

JECTIVE: DNA methylation, a regulator of gene expression, plays an important role in diverse biological processes including developmental process, carcinogenesis and aging. In particular, aberrant DNA methylation has been largely observed in several types of cancers. Currently, it is important to extract disease-specific gene sets associated with the regulation of DNA methylation.MATERIALS AND METHODS: Here we propose a novel approach to find the minimum regulatory units of genes, co-methylated and co-expressed gene pairs (MEGP) that are highly correlated gene pairs between DNA methylation and gene expression showing the co-regulatory relationship. To evaluate whether our method is applicable to extract disease-associated genes, we applied our method to a large-scale dataset from the Cancer Genome Atlas extracting significantly associated MEGP and analyzed their functional correlation.RESULTS: We observed that many MEGP physically interacted with each other and showed high semantic similarity with gene ontology terms. Furthermore, we performed gene set enrichment tests to identify how they are correlated in a complex biological process. Our MEGP were highly enriched in the biological pathway associated with ovarian cancers.CONCLUSIONS: Our approach is useful for discovering coordinated epigenetic markers associated with specific diseases.

Resumo Limpo

jectiv dna methyl regul gene express play import role divers biolog process includ development process carcinogenesi age particular aberr dna methyl larg observ sever type cancer current import extract diseasespecif gene set associ regul dna methylationmateri method propos novel approach find minimum regulatori unit gene comethyl coexpress gene pair megp high correl gene pair dna methyl gene express show coregulatori relationship evalu whether method applic extract diseaseassoci gene appli method largescal dataset cancer genom atlas extract signific associ megp analyz function correlationresult observ mani megp physic interact show high semant similar gene ontolog term furthermor perform gene set enrich test identifi correl complex biolog process megp high enrich biolog pathway associ ovarian cancersconclus approach use discov coordin epigenet marker associ specif diseas

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