Rank-Similarity Measures for Comparing Gene Prioritizations: A Case Study in Autism

J Comput Biol. 2021 Mar;28(3):283-295. doi: 10.1089/cmb.2020.0244. Epub 2020 Oct 27.

Abstract

We discuss the challenge of comparing three gene prioritization methods: network propagation, integer linear programming rank aggregation (RA), and statistical RA. These methods are based on different biological categories and estimate disease-gene association. Previously proposed comparison schemes are based on three measures of performance: receiver operating curve, area under the curve, and median rank ratio. Although they may capture important aspects of gene prioritization performance, they may fail to capture important differences in the rankings of individual genes. We suggest that comparison schemes could be improved by also considering recently proposed measures of similarity between gene rankings. We tested this suggestion on comparison schemes for prioritizations of genes associated with autism that were obtained using brain- and tissue-specific data. Our results show the effectiveness of our measures of similarity in clustering brain regions based on their relevance to autism.

Keywords: autism; comparative analysis; disease–gene association; gene prioritization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Autistic Disorder / genetics*
  • Brain / pathology
  • Cluster Analysis
  • Gene Regulatory Networks / genetics
  • Genetic Predisposition to Disease / genetics
  • Humans