Phylogenetic Profiling for Probing the Modular Architecture of the Human Genome.

Phylogenetic Profiling for Probing the Modular Architecture of the Human Genome.
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DOI:
10.1016/j.cels.2015.08.006
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发表时间:
2015-08-26
期刊:
影响因子:
9.3
通讯作者:
Meyer T
Meyer T
中科院分区:
生物学1区
文献类型:
--
作者:
Dey G;Meyer T

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基因之间功能联系的信息可以从其同源物在多个物种中偶联损失的模式中得到。这种被称为系统发育分析的比较方法已经成功地用于推断细菌和真核生物的遗传相互作用。真核物种测序的快速进展使人类基因组的系统发育分析成为可能,从而对未表征的人类基因进行系统的功能预测。重要的是,共同进化的基因群揭示了潜在遗传网络中广泛的模块化,促进了人类细胞的实验分析以及跨物种保守功能模块的比较研究。这种策略在鉴定新的代谢蛋白和多蛋白复合物组分方面特别成功。其他关键真核生物的目标测序和改进方法的结合来生成和比较系统发育图谱,将进一步提高这种进化方法在基因相互作用网络功能分析中的预测能力和实用性。
Information about functional connections between genes can be derived from patterns of coupled loss of their homologs across multiple species. This comparative approach, termed phylogenetic profiling, has been successfully used to infer genetic interactions in bacteria and eukaryotes. Rapid progress in sequencing eukaryotic species has enabled the recent phylogenetic profiling of the human genome, resulting in systematic functional predictions for uncharacterized human genes. Importantly, groups of co-evolving genes reveal widespread modularity in the underlying genetic network, facilitating experimental analyses in human cells as well as comparative studies of conserved functional modules across species. This strategy is particularly successful in identifying novel metabolic proteins and components of multi-protein complexes. The targeted sequencing of additional key eukaryotes and the incorporation of improved methods to generate and compare phylogenetic profiles will further boost the predictive power and utility of this evolutionary approach to the functional analysis of gene interaction networks.
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