Open Issues for Protein Function Assignment in Haloferax volcanii and Other Halophilic Archaea.
Open Issues for Protein Function Assignment in Haloferax volcanii and Other Halophilic Archaea.
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在Haloferax火山和其他卤素古细菌中蛋白质功能分配的开放问题。
DOI：
10.3390/genes12070963
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发表时间：
2021-06-24
期刊：
影响因子：
3.5
通讯作者：
Dyall-Smith M
中科院分区：
文献类型：
--
作者：
Pfeiffer F;Dyall-Smith M
背景：注释歧义和注释错误是基因组学中的普遍挑战。虽然可以通过实验表征获得可靠的蛋白质功能分配，但这既昂贵又耗时，并且与通常通过自动化管道通过序列同源性注释的蛋白质相比，具有实验支持的此类黄金标准蛋白质（GSP）的数量仍然非常低。即使 GSP 在用作参考时也可能给出误导性的分配：同系物可能足够接近以支持同功能性，但所注释的物种中不存在 GSP 的底物。在这种情况下，酶不能是同功能的。在这里，我们研究了嗜盐古菌（盐细菌纲）中的各种此类问题，重点关注模型盐古菌 Haloferax volcanii。结果：Hfx 的注释蛋白质。公共数据库倾向于为火山分配一个可能不正确的功能。在某些情况下，可以从现有证据中预测或推断出可能正确的替代功能，但这尚未被公共数据库采用，因为缺乏实验验证。在其他情况下，通过同源性预测可能无效的特定功能，虽然有证据表明该分配的功能不太可能，但真正的功能仍然难以捉摸。我们列出了其中 50 个案例，每个案例都有详细的背景信息，以便可以得出最可能的生物学功能的结论。出于简洁和理解的原因，正文中仅列出了关键方面，补充材料的相应部分中提供了详细信息。结论：编译、描述和总结这些开放注释问题和功能预测将有利于科学界改善蛋白质功能分配的评估并更彻底地详细说明它们。通过强调当前数据库中的差距和可能的注释错误，我们希望这项研究将为实验者提供一个框架，以系统地证实（或反驳）我们的功能预测或发现更多意想不到的功能。
Background: Annotation ambiguities and annotation errors are a general challenge in genomics. While a reliable protein function assignment can be obtained by experimental characterization, this is expensive and time-consuming, and the number of such Gold Standard Proteins (GSP) with experimental support remains very low compared to proteins annotated by sequence homology, usually through automated pipelines. Even a GSP may give a misleading assignment when used as a reference: the homolog may be close enough to support isofunctionality, but the substrate of the GSP is absent from the species being annotated. In such cases, the enzymes cannot be isofunctional. Here, we examined a variety of such issues in halophilic archaea (class Halobacteria), with a strong focus on the model haloarchaeon Haloferax volcanii. Results: Annotated proteins of Hfx. volcanii were identified for which public databases tend to assign a function that is probably incorrect. In some cases, an alternative, probably correct, function can be predicted or inferred from the available evidence, but this has not been adopted by public databases because experimental validation is lacking. In other cases, a probably invalid specific function is predicted by homology, and while there is evidence that this assigned function is unlikely, the true function remains elusive. We listed 50 of those cases, each with detailed background information, so that a conclusion about the most likely biological function can be drawn. For reasons of brevity and comprehension, only the key aspects are listed in the main text, with detailed information being provided in a corresponding section of the Supplementary Materials. Conclusions: Compiling, describing and summarizing these open annotation issues and functional predictions will benefit the scientific community in the general effort to improve the evaluation of protein function assignments and more thoroughly detail them. By highlighting the gaps and likely annotation errors currently in the databases, we hope this study will provide a framework for experimentalists to systematically confirm (or disprove) our function predictions or to uncover yet more unexpected functions.
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