Integration of curated databases to identify genotype-phenotype associations.

Integration of curated databases to identify genotype-phenotype associations.
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DOI:
10.1186/1471-2164-7-257
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发表时间:
2006-10-12
期刊:
影响因子:
4.4
通讯作者:
Gerstein M
Gerstein M
中科院分区:
生物学2区
文献类型:
--
作者:
Goh CS;Gianoulis TA;Liu Y;Li J;Paccanaro A;Lussier YA;Gerstein M

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快速表征未知微生物的能力对于应对传染病和生物防御都至关重要。要做到这一点,我们需要某种方法来预测生物体的表型,基于其基因组编码的分子。然而,微生物的分子组成(即基因型)和表型之间的联系并不明显。虽然已经有几项研究解决了这一挑战,但还没有人提出一种大规模的方法来整合策划的生物信息。在这里,我们利用一个系统的方法来发现基因型-表型的关联,结合生物医学信息学数据库,GIDEON的表型信息,与国家生物技术信息中心的Orthopathy组数据库(NCBI COG)的集群中包含的分子信息。整合两个数据库中的信息,我们能够将微生物中给定蛋白质的存在或不存在与其表型相关联,所述表型通过某些形态特征或在特定生长培养基中的存活来测量。在0.8的相关性阈值下,66%的相关性被文献证实,在0.9的相关性阈值下,86%的相关性被证实。我们的研究结果表明,可能的表型表现与糖代谢和电子传递的蛋白质生化。此外,我们相信我们的方法可以扩展到连接致病表型与功能相关的蛋白质。
The ability to rapidly characterize an unknown microorganism is critical in both responding to infectious disease and biodefense. To do this, we need some way of anticipating an organism's phenotype based on the molecules encoded by its genome. However, the link between molecular composition (i.e. genotype) and phenotype for microbes is not obvious. While there have been several studies that address this challenge, none have yet proposed a large-scale method integrating curated biological information. Here we utilize a systematic approach to discover genotype-phenotype associations that combines phenotypic information from a biomedical informatics database, GIDEON, with the molecular information contained in National Center for Biotechnology Information's Clusters of Orthologous Groups database (NCBI COGs). Integrating the information in the two databases, we are able to correlate the presence or absence of a given protein in a microbe with its phenotype as measured by certain morphological characteristics or survival in a particular growth media. With a 0.8 correlation score threshold, 66% of the associations found were confirmed by the literature and at a 0.9 correlation threshold, 86% were positively verified. Our results suggest possible phenotypic manifestations for proteins biochemically associated with sugar metabolism and electron transport. Moreover, we believe our approach can be extended to linking pathogenic phenotypes with functionally related proteins.
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