The evidence that any protein exists in the Human Proteome Project (HPP; protein evidence 1 or PE1) has revolved primarily (though not exclusively) around mass spectrometry (MS) (93% of PE1 proteins have MS evidence in the latest neXtProt release), with robust and stringent, well-curated metrics that have served the community well. This has led to a significant number of proteins still considered ‘missing’ (i.e., PE2-4). Many PE2-4 proteins have either MS evidence of unacceptable quality (small or not enough unitypic peptides and unacceptably high protein/peptide FDRs), transcriptomic and/or antibody evidence. Here we use a Chromosome 7 PE2 example called Prestin, to demonstrate that clear and robust criteria/metrics need to be developed for proteins that may not/cannot produce clear-cut MS evidence, whilst possessing significant non-MS evidence, including disease-association data. Many of the PE2-4 proteins are either inaccessible, spatio-temporally expressed in a limited way or expressed at such a very low copy number as to be unable to be detected by current MS methodologies. We propose that the HPP community consider and lead a communal initiative to accelerate the discovery and characterization of these types of ‘missing’ proteins.

中文翻译：

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人类Prestin：缺乏严格的质谱证据的候选PE1蛋白？

在人类蛋白质组计划中存在任何蛋白质的证据（HPP；蛋白质证据1或PE1）主要（尽管不是排他性地）围绕着质谱法（MS）旋转（93％的PE1蛋白质在最新的neXtProt版本中具有MS证据），强大，严格，精心策划的指标为社区带来了良好的效果。这导致仍然被认为是“缺失”的大量蛋白质（即PE2-4）。许多PE2-4蛋白具有质量不可接受的MS证据（单一或较小的统一肽和不足的高蛋白/肽FDR），转录组和/或抗体证据。在这里，我们使用一个名为Prestin的7号染色体PE2实例来证明，对于可能/不能产生清晰MS证据同时拥有大量非MS证据的蛋白质，需要开发出清晰而稳健的标准/指标，包括疾病关联数据。许多PE2-4蛋白要么难以接近，要么时空表达受限，要么以非常低的拷贝数表达，以致于目前的MS方法无法检测到。我们建议HPP社区考虑并领导一项共同行动，以加速发现和表征这些类型的“缺失”蛋白质。