Abstract

Discovering genetic basis of diseases is an important goal and a challenging problem in bioinformatics research. Inspired by network-based global inference approach, Semi-global inference method is proposed to capture the complex associations between phenotypes and genes. The proposed method integrates phenotype similarities and protein-protein interactions, and it establishes the profile vectors of phenotypes and proteins. Then the relevance between each candidate gene and the target phenotype is evaluated. Candidate genes are then ranked according to relevance mark and genes that are potentially associated with target disease are identified based on this ranking. The model selects nodes in integrated phenotype-protein network for inference, by exploiting Phenotype Similarity Threshold (PST), which throws lights on selection of similar phenotypes for gene prediction problem. Different vector relevance metrics for computing the relevance marks of candidate genes are discussed. The performance of the model is evaluated on Online Mendelian Inheritance in Man (OMIM) data sets and experimental evaluation shows high performance of proposed Semi-global method outperforms existing global inference methods.

Highlights

  • It is challenging for biomedical research to figure out the genetic basis of diseases

  • The candidate set C contains candidate genes, one or more of which is potentially associated with target disease d

  • We comprehensively evaluate the performance of proposed Semi-global inference model with different setting of metrics and Phenotype Similarity Threshold (PST)

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Summary

Introduction

It is challenging for biomedical research to figure out the genetic basis of diseases. The methods rely on functional annotations are limited because only a small part of genes in the genome have been annotated currently and methods based on sequencing is an expensive task They treated disease genes as separate and independent, biological processes are not realized by a single molecule, but rather by the complex interactions of proteins, and the breakdown in protein interaction networks could result in diseases [6]. Some research indicates that phenotypically similar diseases are caused by functionally related genes [7], and the proteins coded by these functionally related genes usually have direct or indirect interactions [8] From this perspective, disease genes could be investigated through the interaction networks of disease proteins.

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