A Survey of Gene Prioritization Tools for Mendelian and Complex Human Diseases.

Olga Zolotareva,Maren Kleine

doi:10.1515/jib-2018-0069

Abstract

Modern high-throughput experiments provide us with numerous potential associations between genes and diseases. Experimental validation of all the discovered associations, let alone all the possible interactions between them, is time-consuming and expensive. To facilitate the discovery of causative genes, various approaches for prioritization of genes according to their relevance for a given disease have been developed. In this article, we explain the gene prioritization problem and provide an overview of computational tools for gene prioritization. Among about a hundred of published gene prioritization tools, we select and briefly describe 14 most up-to-date and user-friendly. Also, we discuss the advantages and disadvantages of existing tools, challenges of their validation, and the directions for future research.

Highlights

Gene prioritization problem emerged together with the growth of popularity of genetic linkage analysis
Among about a hundred of gene prioritization tools published to date, we selected and described 14 most promising ones on the basis of their availability, usability, and novelty
We classified gene prioritization tools according to underlying assumptions, methodology, and data representation models

Summary

Introduction

Gene prioritization problem emerged together with the growth of popularity of genetic linkage analysis. Genetic mapping yielded large loci containing many candidate genes, only a few of which were associated with the investigated phenotype. In 2006 Aerts et al [2] prioritized 58 candidate genes from a 2-Mb region of chromosome 22 according to their similarity with known disease genes in ten distinct evidence sources. They predicted YPEL1 as a novel gene involved in atypical DiGeorge syndrome (DGS) and validated this prediction in vivo: knock-down of YPEL1 homolog in Zebrafish embryos led to craniofacial defects and confirmed its role in pharyngeal arch morphogenesis [2]

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Conclusion