Abstract

BackgroundCandidate gene prioritization aims to identify promising new genes associated with a disease or a biological process from a larger set of candidate genes. In recent years, network-based methods – which utilize a knowledge network derived from biological knowledge – have been utilized for gene prioritization. Biological knowledge can be encoded either through the network's links or nodes. Current network-based methods can only encode knowledge through links. This paper describes a new network-based method that can encode knowledge in links as well as in nodes.ResultsWe developed a new network inference algorithm called the Knowledge Network Gene Prioritization (KNGP) algorithm which can incorporate both link and node knowledge. The performance of the KNGP algorithm was evaluated on both synthetic networks and on networks incorporating biological knowledge. The results showed that the combination of link knowledge and node knowledge provided a significant benefit across 19 experimental diseases over using link knowledge alone or node knowledge alone.ConclusionsThe KNGP algorithm provides an advance over current network-based algorithms, because the algorithm can encode both link and node knowledge. We hope the algorithm will aid researchers with gene prioritization.

Highlights

  • Understanding the genetic and biological mechanisms of diseases is an ongoing challenge

  • Since there are no existing network-based inference algorithms that can utilize node knowledge, we developed a new network-based method called the Knowledge Network Gene Prioritization (KNGP) algorithm that utilizes link and node knowledge

  • We describe the components of the KNGP algorithm in detail

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Summary

Introduction

Understanding the genetic and biological mechanisms of diseases is an ongoing challenge. Several high-throughput techniques that survey a large number of genes have been developed for elucidating the genetic factors of common diseases. Such techniques include gene expression profiling, genotyping of single nucleotide polymorphisms, and whole genome sequencing to name just a few. One challenge with such techniques is that they typically produce hundreds of candidate genes associated with the disease of interest. This paper describes a new network-based method that can encode knowledge in links as well as in nodes

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