Interactome-transcriptome analysis discovers signatures complementary to GWAS Loci of Type 2 Diabetes
Publication in refereed journal


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摘要Protein interactions play significant roles in complex diseases. We analyzed peripheral blood mononuclear cells (PBMC) transcriptome using a multi-method strategy. We constructed a tissue-specific interactome (T2Di) and identified 420 molecular signatures associated with T2D-related comorbidity and symptoms, mainly implicated in inflammation, adipogenesis, protein phosphorylation and hormonal secretion. Apart from explaining the residual associations within the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) study, the T2Di signatures were enriched in pathogenic cell type-specific regulatory elements related to fetal development, immunity and expression quantitative trait loci (eQTL). The T2Di revealed a novel locus near a well-established GWAS loci AChE, in which SRRT interacts with JAZF1, a T2D-GWAS gene implicated in pancreatic function. The T2Di also included known anti-diabetic drug targets (e.g. PPARD, MAOB) and identified possible druggable targets (e.g. NCOR2, PDGFR). These T2Di signatures were validated by an independent computational method, and by expression data of pancreatic islet, muscle and liver with some of the signatures (CEBPB, SREBF1, MLST8, SRF, SRRT and SLC12A9) confirmed in PBMC from an independent cohort of 66 T2D and 66 control subjects. By combining prior knowledge and transcriptome analysis, we have constructed an interactome to explain the multi-layered regulatory pathways in T2D.
著者Li JW, Lee HM, Wang Y, Tong AHY, Yip KY, Tsui SKW, Lok S, Ozaki R, Luk AO, Kong APS, So WY, Ma RCW, Chan JCN, Chan TF
期刊名稱Scientific Reports
出版年份2016
月份10
日期18
卷號6
出版社NATURE PUBLISHING GROUP
國際標準期刊號2045-2322
電子國際標準期刊號2045-2322
語言英式英語
Web of Science 學科類別Multidisciplinary Sciences; Science & Technology - Other Topics

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