Additional Supporting Information may be found in the online version of this article.
Prioritization of Retinal Disease Genes: An Integrative Approach
Article first published online: 12 APR 2013
© 2013 Wiley Periodicals, Inc.
Volume 34, Issue 6, pages 853–859, June 2013
How to Cite
Wagner, A. H., Taylor, K. R., DeLuca, A. P., Casavant, T. L., Mullins, R. F., Stone, E. M., Scheetz, T. E. and Braun, T. A. (2013), Prioritization of Retinal Disease Genes: An Integrative Approach. Hum. Mutat., 34: 853–859. doi: 10.1002/humu.22317
Communicated by Barend Mons
Contract grant sponsor: National Institute of General Medical Sciences Bioinformatics Award (Grant T32GM082729).
- Issue published online: 20 MAY 2013
- Article first published online: 12 APR 2013
- Accepted manuscript online: 18 MAR 2013 08:10AM EST
- Manuscript Accepted: 7 MAR 2013
- Manuscript Received: 21 AUG 2012
- National Institute of General Medical Sciences Bioinformatics Award. Grant Number: T32GM082729
- machine learning;
- data integration;
- gene prioritization;
The discovery of novel disease-associated variations in genes is often a daunting task in highly heterogeneous disease classes. We seek a generalizable algorithm that integrates multiple publicly available genomic data sources in a machine-learning model for the prioritization of candidates identified in patients with retinal disease. To approach this problem, we generate a set of feature vectors from publicly available microarray, RNA-seq, and ChIP-seq datasets of biological relevance to retinal disease, to observe patterns in gene expression specificity among tissues of the body and the eye, in addition to photoreceptor-specific signals by the CRX transcription factor. Using these features, we describe a novel algorithm, positive and unlabeled learning for prioritization (PULP). This article compares several popular supervised learning techniques as the regression function for PULP. The results demonstrate a highly significant enrichment for previously characterized disease genes using a logistic regression method. Finally, a comparison of PULP with the popular gene prioritization tool ENDEAVOUR shows superior prioritization of retinal disease genes from previous studies. The java source code, compiled binary, assembled feature vectors, and instructions are available online at https://github.com/ahwagner/PULP.