Assessing identity, redundancy and confounds in Gene Ontology annotations over time

MOTIVATION: The Gene Ontology (GO) is heavily used in systems biology, but the potential for redundancy, confounds with other data sources and problems with stability over time have been little explored. RESULTS: We report that GO annotations are stable over short periods, with 3% of genes not being most semantically similar to themselves between monthly GO editions. However, we find that genes can alter their 'functional identity' over time, with 20% of genes not matching to themselves (by semantic similarity) after 2 years. We further find that annotation bias in GO, in which some genes are more characterized than others, has declined in yeast, but generally increased in humans. Finally, we discovered that many entries in protein interaction databases are owing to the same published reports that are used for GO annotations, with 66% of assessed GO groups exhibiting this confound. We provide a case study to illustrate how this information can be used in analyses of gene sets and networks. AVAILABILITY: Data available at http://chibi.ubc.ca/assessGO.研究动机：基因本体论（Gene Ontology，GO）在系统生物学领域应用极为广泛，但有关其潜在的冗余性、与其他数据源的混杂性以及随时间推移的稳定性问题，目前相关研究仍较为匮乏。 研究结果：本研究表明，GO注释在短期内具备稳定性：在每月更新的GO版本间，仅有3%的基因无法在语义相似度上与自身保持最高匹配度。然而，我们同时发现，基因的‘功能身份’会随时间发生变化：两年后，有20%的基因无法通过语义相似度与自身匹配。进一步研究显示，GO注释偏倚——即部分基因相较于其他基因获得了更多的功能注释——在酵母中有所缓解，但在人类中整体呈上升趋势。最后，我们发现蛋白质相互作用数据库中的大量条目，其来源与用于生成GO注释的已发表文献完全一致，66%的被评估GO组均存在这一混杂问题。我们还提供了一则案例研究，用以说明该研究结果可如何应用于基因集与基因网络的分析工作中。 数据获取：相关数据集可通过http://chibi.ubc.ca/assessGO 获取。