Impact of outdated gene annotations on pathway enrichment analysis

By Lina Wadi, Mona Meyer, Joel Weiser, Lincoln D. Stein, Jüri Reimand. 2016

121 citations recorded by the source corpus.

To the Editor: Pathway enrichment analysis is a common technique for interpreting gene lists derived from high-throughput experiments1. Its success depends on the quality of gene annotations. We analyzed the evolution of pathway knowledge and annotations over the past seven years and found that the use of outdated resources has strongly affected practical genomic analysis and recent literature: 67% of ~3,900 publications we surveyed in 2015 referenced outdated software that captured only 26% of biological processes and pathways identified using current resources. Pathway analysis assesses the statistical enrichment of biological processes and pathways in a given gene list on the basis of information in Gene Ontology2 (GO) and pathway databases such as Reactome3 and PathwayCommons. GO is updated daily and Reactome versions are released quarterly, but many software tools interpret gene lists using functional information that has not been updated for years. We surveyed the update times of 25 web-based pathway enrichment tools and citations of these tools in 3,879 publications (Fig. 1a and Supplementary Tables 1 and 2). Although nine tools (for example, g:Profiler4 and PANTHER5) provided gene annotations that had been revised within six months (September 2015 through February 2016), most tools were outdated by several years. Ten (42%) were

Subfields: Molecular Biology

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Citations in the corpus

Expansion of the Gene Ontology knowledgebase and resources (2016, background): “In addition, recent studies have shown that many enrichment tools use outdated versions of the ontology or annotations, strongly impacting analyses (19).”
Using clusterProfiler to characterize multiomics data (2024, unknown): “Opting for inaccurate or outdated annotation information can introduce profound and irreversible biases to the conclusions of research analysis 61,62 .”
g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update) (2019, background): “Therefore the users need to have a critical mind to recognize services that ignore data updates and might miss relevant new findings (37).”
MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis (2018, background): “To address potential issues such as the decline in analysis quality due to a lack of updated annotations (18,19), we have put considerable effort into updating MetaboAnalyst’s underlying knowledgebase.”
g:Profiler—interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update) (2023, unknown): “Updates to data can alter analysis results over time, creating potential confusion for colleagues and discrepancies between pre viously pub lished and ne w results ( 11 ).”
A novel community driven software for functional enrichment analysis of extracellular vesicles data (2017, methodology): “enrichment analysis tools do not allow the users to control the databases nor to update them in real time [8].”