Table S4 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 <i>S. pombe</i>, 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，催生了未知蛋白质表征研究的爆发式增长。近年来，蛋白质功能发现的步伐已然放缓，即便在研究较为充分的模式生物中，仍有约20%的蛋白质缺乏其生物学功能的有效注释。值得注意的是，诸多未被表征的蛋白质从酵母到人类均具有保守性，这提示它们参与了核心生物学过程（Biological Process, BP）。要全面理解健康与疾病状态下的生物系统，我们必须厘清该系统的每一个组成部分。因此，未被研究的蛋白质是一个集体性的研究盲区，制约了基础与应用生物科学的发展。我们基于基因本体（Gene Ontology, GO）的生物学过程（Biological Process, BP）术语，构建了一种简洁却高效的度量标准，用于界定人类、酿酒酵母与裂殖酵母中的已表征与未表征蛋白质。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，并结合大规模实验与比较分析方法得到的正交属性对其进行分类。最后，我们探讨了这些蛋白质长期被忽视的潜在原因，并提出了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注释目录获取相应的研究价值。