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Enhanced MissingProteins Detection in NCI60 CellLines Using an Integrative Search Engine Approach

机译:增强缺失NCI60细胞中的蛋白质检测行使用集成搜索引擎方法

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摘要

The Human Proteome Project (HPP) aims deciphering the complete map of the human proteome. In the past few years, significant efforts of the HPP teams have been dedicated to the experimental detection of the missing proteins, which lack reliable mass spectrometry evidence of their existence. In this endeavor, an in depth analysis of shotgun experiments might represent a valuable resource to select a biological matrix in design validation experiments. In this work, we used all the proteomic experiments from the NCI60 cell lines and applied an integrative approach based on the results obtained from Comet, Mascot, OMSSA, and X!Tandem. This workflow benefits from the complementarity of these search engines to increase the proteome coverage. Five missing proteins C-HPP guidelines compliant were identified, although further validation is needed. Moreover, 165 missing proteins were detected with only one unique peptide, and their functional analysis supported their participation in cellular pathways as was also proposed in other studies. Finally, we performed a combined analysis of the gene expressionlevels and the proteomic identifications from the common cell linesbetween the NCI60 and the CCLE project to suggest alternatives forfurther validation of missing protein observations.
机译:人类蛋白质组计划(HPP)旨在破译人类蛋白质组的完整图谱。在过去的几年中,HPP团队付出了巨大的努力来对缺失的蛋白质进行实验检测,这些蛋白质缺乏可靠的质谱证据来证明它们的存在。为此,对shot弹枪实验进行深入分析可能代表了在设计验证实验中选择生物基质的宝贵资源。在这项工作中,我们使用了来自NCI60细胞系的所有蛋白质组学实验,并基于从Comet,Mascot,OMSSA和X!Tandem获得的结果应用了整合方法。这些工作流的互补性使该工作流程受益,以增加蛋白质组覆盖率。鉴定了五种符合C-HPP指导原则的缺失蛋白,尽管还需要进一步验证。此外,只有一种独特的肽可以检测到165种缺失的蛋白质,其功能分析也支持它们参与细胞途径,这在其他研究中也被提出。最后,我们对基因表达进行了综合分析常见细胞系的水平和蛋白质组学鉴定在NCI60和CCLE项目之间提出建议进一步验证缺失的蛋白质观察结果。

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