Table S11 from Hidden in plain sight: what remains to be discovered in the eukaryotic proteome?

The first decade of genome sequencing stimulated an explosion in the characterization of unknown proteins. More recently, the pace of functional discovery has slowed, leaving around 20% of the proteins even in well-studied model organisms without informative descriptions of their biological roles. Remarkably, many uncharacterized proteins are conserved from yeasts to human, suggesting that they contribute to fundamental biological processes (BP). To fully understand biological systems in health and disease, we need to account for every part of the system. Unstudied proteins thus represent a collective blind spot that limits the progress of both basic and applied biosciences. We use a simple yet powerful metric based on gene ontology BP terms to define characterized and uncharacterized proteins for human, budding yeast and fission yeast. We then identify a set of conserved but unstudied proteins in S. pombe, and classify them based on a combination of orthogonal attributes determined by large-scale experimental and comparative methods. Finally, we explore possible reasons why these proteins remain neglected, and propose courses of action to raise their profile and thereby reap the benefits of completing the catalogue of proteins’ biological roles.

基因组测序的首个十年，推动了未知蛋白质功能表征研究的爆发式增长。近年来，蛋白质功能解析的节奏已然放缓，即便在研究较为充分的模式生物中，仍有约20%的蛋白质尚未得到其生物学功能的详实阐释。值得注意的是，诸多未被表征的蛋白质在酵母至人类之间均存在保守性，这提示它们参与了核心生物学过程（Biological Process, BP）。为全面理解健康与疾病状态下的生物学系统，我们需要阐明该系统的每一个组成部分。因此，未被研究的蛋白质构成了一处整体性认知盲区，制约了基础与应用生物科学的发展。本研究采用基于基因本体论生物过程（Gene Ontology Biological Process, BP）术语的简洁高效指标，对人类、酿酒酵母与裂殖酵母的已表征与未表征蛋白质进行界定。随后，我们在裂殖酵母（S. pombe）中筛选得到一组保守但未被研究的蛋白质，并基于大规模实验与比较分析方法所得到的正交属性组合对其进行分类。最后，我们探讨了这些蛋白质长期被忽视的潜在原因，并提出提升其研究关注度的行动方案，以期通过完善蛋白质生物学功能目录而获得相应收益。