Protein Interaction and Disease Gene Prioritization

Abstract

Gene prioritization is a new approach for extending our knowledge about diseases and phenotypic information each gene encodes. The general notion of gene prioritization assumes that one has a set of candidates and he wants to order the candidates from the most promising to the least promising one. A primary motivation for prioritization of candidate disease genes comes from the analysis of linkage regions that contain genetic elements of diseases. The notion of a disease gene is unambiguous: a genetic element that confers disease susceptibility if its variants are present in the genome. For a particular disease phenotype, we often have a list of candidate genes usually genes located in a linkage interval associated with the disease. Finding the actual gene and candidate can be a subject of expensive experimental validations; however, once identified as real, these disease-associated genes or their protein products can be considered as a therapeutic target or a diagnostic biomarker. Online Mendelian Inheritance in Man (OMIM) is a representative database that links phenotypes, genomic regions, and genes. To make effective use of biological resources, computational gene prioritization allows us to choose the best candidate genes for subsequent experimental validations. In this chapter, we represent the methodology for the pathway of the candidate genes related to ADHD, dementia, mood disorder, OCD, and schizophrenia. The pathway is required because of since not all genes affect significantly for the cause of the disease. Hence, they should be prioritized according to their significance. We have taken that gene–gene interaction data and their corresponding network are used to prioritize these genes according to their interaction with the targeted genes mapped to a particular disease pathway. Section 1 represents the prioritization using interaction network. Section 2 discusses for the pathways. Section 3 represents the target, mapped, and reference genes for ADHD, dementia, mood disorder, OCD, and schizophrenia. Section 4 represents disease gene prioritization using random walk with restart. Section 5 concludes RWR method to help us find genes and to reach to the conclusion of the highly interacted genes network formation for the above disease prioritization.