Utilization of the Proteome Data Deposited in SRMAtIas for Validating the Existence of the Human Missing Proteins in GPM
Utilization of the Proteome Data Deposited in SRMAtIas for Validating the Existence of the Human Missing Proteins in GPM
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DOI：
10.1021/acs.jproteome.9b00355
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发表时间：
2019-12-01
影响因子：
4.4
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
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作者：
Elguoshy, Amr;Hirao, Yoshitoshi;Yamamoto, Tadashi
自2012年以来，人类蛋白质组计划(HPP)一直在努力澄清人类蛋白质的现有证据。然而，根据最近发布的neXtProt(2019-1)，大约10%的人类基因仍然没有足够的或没有实验证据表明它们在蛋白质水平上的翻译。它们被归类为缺失蛋白(PE2-PE4)。为了进一步实现HPP的目标，我们开发了一个两步生物信息学策略，利用与缺失蛋白质相对应的SRMAtlas合成肽作为独家参考，以探索它们在GPM中的自然对应。在第一步中，我们在GPM中搜索与缺失的蛋白质相对应的非嵌套SRMAtlas多肽，仅考虑在同一蛋白质组研究中通过>；=2个长度为>；=9个氨基酸的非嵌套单位/蛋白型肽“链状多肽”检测到的那些。结果，在35项不同的蛋白质组学研究中，新发现了51种缺失的蛋白质。在第二步中，我们验证了这些新检测到的缺失蛋白质，方法是分别在SRMAtIas和GPM中匹配它们的合成肽和天然肽的光谱。结果表明，在~gt；=2个非嵌套肽缺失的蛋白质中，有23个通过仔细的光谱匹配得到了验证。
The Human Proteome Project (HPP) has made great efforts to clarify the existing evidence of human proteins since 2012. However, according to the recent release of neXtProt (2019-1), approximately 10% of all human genes still have inadequate or no experimental evidence of their translation at the protein level. They were categorized as missing proteins (PE2-PE4). To further the goal of HPP, we developed a two-step bioinformatic strategy addressing the utilization of the SRMAtlas synthetic peptides corresponding to the missing proteins as an exclusive reference in order to explore their natural counterparts within GPM. In the first step, we searched the GPM for the non-nested SRMAtlas peptides corresponding to the missing proteins, taking under consideration only those detected via >= 2 non-nested unitypic/proteotypic peptides "Stranded peptides" with length >= 9 amino acids in the same proteomic study. As a result, 51 missing proteins were newly detected in 35 different proteomic studies. In the second step, we validated these newly detected missing proteins based on matching the spectra of their synthetic and natural peptides in SRMAtIas and GPM, respectively. The results showed that 23 of the missing proteins with >= 2 non-nested peptides were validated by careful spectral matching.