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A Bayesian framework that integrates multi-omics data and gene networks predicts risk genes from schizophrenia GWAS data.

ABSTRACT: Genome-wide association studies (GWAS) have identified more than 100 schizophrenia (SCZ)-associated loci, but using these findings to illuminate disease biology remains a challenge. Here we present integrative risk gene selector (iRIGS), a Bayesian framework that integrates multi-omics data and gene networks to infer risk genes in GWAS loci. By applying iRIGS to SCZ GWAS data, we predicted a set of high-confidence risk genes, most of which are not the nearest genes to the GWAS index variants. High-confidence risk genes account for a significantly enriched heritability, as estimated by stratified linkage disequilibrium score regression. Moreover, high-confidence risk genes are predominantly expressed in brain tissues, especially prenatally, and are enriched for targets of approved drugs, suggesting opportunities to reposition existing drugs for SCZ. Thus, iRIGS can leverage accumulating functional genomics and GWAS data to advance our understanding of SCZ etiology and potential therapeutics.

SUBMITTER: Wang Q

PROVIDER: S-EPMC6646046 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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A Bayesian framework that integrates multi-omics data and gene networks predicts risk genes from schizophrenia GWAS data.

Wang Quan Q Chen Rui R Cheng Feixiong F Wei Qiang Q Ji Ying Y Yang Hai H Zhong Xue X Tao Ran R Wen Zhexing Z Sutcliffe James S JS Liu Chunyu C Cook Edwin H EH Cox Nancy J NJ Li Bingshan B

Nature neuroscience 20190415 5

Genome-wide association studies (GWAS) have identified more than 100 schizophrenia (SCZ)-associated loci, but using these findings to illuminate disease biology remains a challenge. Here we present integrative risk gene selector (iRIGS), a Bayesian framework that integrates multi-omics data and gene networks to infer risk genes in GWAS loci. By applying iRIGS to SCZ GWAS data, we predicted a set of high-confidence risk genes, most of which are not the nearest genes to the GWAS index variants. Hi ...[more]

PMID: 30988527

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Project description:BackgroundLncRNAs (Long non-coding RNAs) are a type of non-coding RNA molecule with transcript length longer than 200 nucleotides. LncRNA has been novel candidate biomarkers in cancer diagnosis and prognosis. However, it is difficult to discover the true association mechanism between lncRNAs and complex diseases. The unprecedented enrichment of multi-omics data and the rapid development of machine learning technology provide us with the opportunity to design a machine learning framework to study the relationship between lncRNAs and complex diseases.ResultsIn this article, we proposed a new machine learning approach, namely LGDLDA (LncRNA-Gene-Disease association networks based LncRNA-Disease Association prediction), for disease-related lncRNAs association prediction based multi-omics data, machine learning methods and neural network neighborhood information aggregation. Firstly, LGDLDA calculates the similarity matrix of lncRNA, gene and disease respectively, and it calculates the similarity between lncRNAs through the lncRNA expression profile matrix, lncRNA-miRNA interaction matrix and lncRNA-protein interaction matrix. We obtain gene similarity matrix by calculating the lncRNA-gene association matrix and the gene-disease association matrix, and we obtain disease similarity matrix by calculating the disease ontology, the disease-miRNA association matrix, and Gaussian interaction profile kernel similarity. Secondly, LGDLDA integrates the neighborhood information in similarity matrices by using nonlinear feature learning of neural network. Thirdly, LGDLDA uses embedded node representations to approximate the observed matrices. Finally, LGDLDA ranks candidate lncRNA-disease pairs and then selects potential disease-related lncRNAs.ConclusionsCompared with lncRNA-disease prediction methods, our proposed method takes into account more critical information and obtains the performance improvement cancer-related lncRNA predictions. Randomly split data experiment results show that the stability of LGDLDA is better than IDHI-MIRW, NCPLDA, LncDisAP and NCPHLDA. The results on different simulation data sets show that LGDLDA can accurately and effectively predict the disease-related lncRNAs. Furthermore, we applied the method to three real cancer data including gastric cancer, colorectal cancer and breast cancer to predict potential cancer-related lncRNAs.

Dataset Information

A Bayesian framework that integrates multi-omics data and gene networks predicts risk genes from schizophrenia GWAS data.

Publications

A Bayesian framework that integrates multi-omics data and gene networks predicts risk genes from schizophrenia GWAS data.

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