PhenoGeneRanker: Gene and Phenotype Prioritization Using Multiplex Heterogeneous Networks

Cagatay Dursun; Anne E. Kwitek; Serdar Bozdag

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PhenoGeneRanker: Gene and Phenotype Prioritization Using Multiplex Heterogeneous Networks

机译：PhenoGeneRanker: Gene and Phenotype Prioritization Using Multiplex Heterogeneous Networks

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Uncovering genotype-phenotype relationships is a fundamental challenge in genomics. Gene prioritization is an important step for this endeavor to make a short manageable list from a list of thousands of genes coming from high-throughput studies. Network propagation methods are promising and state of the art methods for gene prioritization based on the premise that functionally related genes tend to be close to each other in the biological networks. Recently, we introduced PhenoGeneRanker, a network-propagation algorithm for multiplex heterogeneous networks. PhenoGeneRanker allows multi-layer gene and phenotype networks. It also calculates empirical p values of gene and phenotype ranks using random stratified sampling of seeds of genes and phenotypes based on their connectivity degree in the network. In this study, we introduce the PhenoGeneRanker Bioconductor package and its application to multi-omics rat genome datasets to rank hypertension disease-related genes and strains. We showed that PhenoGeneRanker performed better to rank hypertension disease-related genes using multiplex gene networks than aggregated gene networks. We also showed that PhenoGeneRanker performed better to rank hypertension disease-related strains using multiplex phenotype network than single or aggregated phenotype networks. We performed a rigorous hyperparameter analysis and, finally showed that Gene Ontology (GO) enrichment of statistically significant top-ranked genes resulted in hypertension disease-related GO terms.

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《IEEE/ACM transactions on computational biology and bioinformatics》 |2022年第5期|2950-2962|共13页
作者
Cagatay Dursun; Anne E. Kwitek; Serdar Bozdag;
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作者单位

Department of Biomedical Engineering Medical College of Wisconsin, Marquette University, Milwaukee, WI, USA;

Department Physiology, Medical College of Wisconsin, Milwaukee, WI, USA;

Department of Computer Science and Engineering, University of North Texas, Denton, TX, USA;

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正文语种英语
中图分类生物信息论;
关键词
Multiplexing; Heterogeneous networks; Diseases; Hypertension; Biology; Bioinformatics; Rats;

PhenoGeneRanker: Gene and Phenotype Prioritization Using Multiplex Heterogeneous Networks

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