{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:45:08Z","timestamp":1785804308107,"version":"3.56.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"vor","delay-in-days":620,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Many studies have investigated the differential expression of microRNAs (miRNAs) in disease states and between different treatments, tissues and developmental stages. Given a list of perturbed miRNAs, it is common to predict the shared pathways on which they act. The standard test for functional enrichment typically yields dozens of significantly enriched functional categories, many of which appear frequently in the analysis of apparently unrelated diseases and conditions.<\/jats:p><jats:p>Results: We show that the most commonly used functional enrichment test is inappropriate for the analysis of sets of genes targeted by miRNAs. The hypergeometric distribution used by the standard method consistently results in significant P-values for functional enrichment for targets of randomly selected miRNAs, reflecting an underlying bias in the predicted gene targets of miRNAs as a whole. We developed an algorithm to measure enrichment using an empirical sampling approach, and applied this in a reanalysis of the gene ontology classes of targets of miRNA lists from 44 published studies. The vast majority of the miRNA target sets were not significantly enriched in any functional category after correction for bias. We therefore argue against continued use of the standard functional enrichment method for miRNA targets.<\/jats:p><jats:p>Availability and implementation: A Python script implementing the empirical algorithm is freely available at http:\/\/sgjlab.org\/empirical-go\/.<\/jats:p><jats:p>Contact: \u00a0sam.griffiths-jones@manchester.ac.uk or janine.lamb@manchester.ac.uk<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv023","type":"journal-article","created":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T03:50:58Z","timestamp":1421898658000},"page":"1592-1598","source":"Crossref","is-referenced-by-count":108,"title":["Bias in microRNA functional enrichment analysis"],"prefix":"10.1093","volume":"31","author":[{"given":"Thomas","family":"Bleazard","sequence":"first","affiliation":[{"name":"1 Faculty of Medical and Human Sciences, and 2Faculty of Life Sciences, University of Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine A","family":"Lamb","sequence":"additional","affiliation":[{"name":"1 Faculty of Medical and Human Sciences, and 2Faculty of Life Sciences, University of Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Griffiths-Jones","sequence":"additional","affiliation":[{"name":"1 Faculty of Medical and Human Sciences, and 2Faculty of Life Sciences, University of Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,1,20]]},"reference":[{"key":"2023020115450105800_btv023-B1","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1105\/tpc.112.095752","article-title":"Grass microRNA gene paleohistory unveils new insights into gene dosage balance in subgenome partitioning after whole-genome duplication","volume":"24","author":"Abrouk","year":"2012","journal-title":"Plant Cell"},{"key":"2023020115450105800_btv023-B2","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1186\/1471-2407-9-374","article-title":"Characterization of global microRNA expression reveals oncogenic potential of miR-145 in metastatic colorectal cancer","volume":"9","author":"Arndt","year":"2009","journal-title":"BMC Cancer"},{"key":"2023020115450105800_btv023-B3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. 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