Advances in gene ontology utilization improve statistical power of annotation enrichment

Eugene W. Hinderer, Robert M. Flight, Rashmi Dubey, James N. MacLeod, Hunter N.B. Moseley

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the improvements in annotation enrichment by re-interpreting edges that would otherwise be omitted by traditional ancestor path-tracing methods. Specifically, we show that GOcats’ unique handling of relations improves enrichment over conventional methods in the analysis of two different gene-expression datasets: a breast cancer microarray dataset and several horse cartilage development RNAseq datasets. With the breast cancer microarray dataset, we observed significant improvement (one-sided binomial test p-value = 1.86E-25) in 182 of 217 significantly enriched GO terms identified from the conventional path traversal method when GOcats’ path traversal was used. We also found new significantly enriched terms using GOcats, whose biological relevancy has been experimentally demonstrated elsewhere. Likewise, on the horse RNAseq datasets, we observed a significant improvement in GO term enrichment when using GOcat’s path traversal: one-sided binomial test p-values range from 1.32E-03 to 2.58E-44.

Original languageEnglish
Article numbere0220728
JournalPLoS ONE
Issue number8
StatePublished - Aug 1 2019

Bibliographical note

Funding Information:
This work was supported in part by grants NSF 1419282 (to HNBM), NIH 1U24DK097215-01A1 (to HNBM), and NIH UL1TR001998-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study. Contributions of Dr. Emma Adam in collecting the equine tissue samples and generating the RNAseq data are graciously acknowledged.

Publisher Copyright:
© 2019 Hinderer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ASJC Scopus subject areas

  • General


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