Re-annotation of the sequence > annotation: opportunities for the functional microbiologist.

Re-annotation of the sequence > annotation: opportunities for the functional microbiologist.
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DOI:
10.1111/1751-7915.12242
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发表时间:
2015-01
影响因子:
5.7
通讯作者:
Barona-Gómez F
Barona-Gómez F
中科院分区:
工程技术2区
文献类型:
--
作者:
Barona-Gómez F

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蛋白质的功能注释是后基因组时代生物学发展的核心。通过这种方式,由基因组序列编码的丰富信息已经为更广泛的生物界所获取。有人甚至会说,这有助于科学民主化,因为世界上几乎每个科学家都可以访问基因公共数据库和进行相似性Blast搜索所需的少量计算能力。然而,我要在这里指出,这个框架是有缺陷的,因为它坚持了一个曾经非常有用,但现在有限和简单的假设,即“任何发现适用于大肠杆菌的东西也一定适用于大象”,这是雅克·莫诺(Jacques Monod)大约半个世纪前的著名论断。在最常见的注释过程中,我们用功能属性标记生物分子,这些生物分子编码在任何给定的基因组中,现在甚至由小型实验室进行常规测序。注释依赖于序列相似性搜索和已知的不同生物体中相似生物分子的分子生物学功能。由于后一种知识,例如糖酵解途径,首先是在大肠杆菌等模式生物中获得的,功能注释是关于使用敏感的生物信息学算法检测(远程!)同源物,然后将来自知名模式生物的功能“实验验证”数据传播到我们遥远的相关研究主题。但是,当前被广泛接受的用于功能注释的方法有哪些限制呢?更重要的是,对于这个领域和新一代的“功能微生物学家”来说,未来的研究机会是什么?我将在这篇文章中为这些问题提供一些初步的答案。仔细考虑当前的概念性功能注释时,至少可以预见到两个问题
Functional annotation of proteins has been central to the development of biology in the post-genomic era. In such a way, the wealth of information encoded by genome sequences has become accessible to the broader biological community. One may even argue that this has served the purpose of democratization of science, as almost every scientist in the world has access to both genetic public databases and the little computing power needed for doing similarity Blast searches. However, I will argue here that this framework is flawed as it sticks to the once very useful, but now limited and simplistic assumption, that ‘anything found to be true of E. coli must also be true of elephants’, a famous statement by Jacques Monod around half a century ago.In the most common annotation process, we label biomolecules, coded for in any given genome now routinely sequenced even by small laboratories, with a functional attribute. Annotation relies on sequence similarity searches and in what is known about the molecular biological functions of similar biomolecules in diverse organisms. As the latter knowledge, for instance the glycolytic pathway, was first obtained in model organisms such as Escherichia coli, functional annotation is about detecting (remote!) homologues using sensitive bioinformatics algorithms, and subsequent propagation of functional ‘experimentally validated’data from the well-known model organisms, to our distantly related subject of study. But what are the limitations associated with the current and broadly accepted approach used for functional annotation? And more importantly, what may be future research opportunities for the field and for the new generation of ‘functional microbiologists’ armed with both computational and wet laboratory experimental tools? Providing some preliminary answers to these questions is what I will aim at in this piece. At least two problems can be envisioned when carefully considering the current conceptual functional annotation
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