Kensche Philip R, van Noort Vera, Dutilh Bas E, Huynen Martijn A
Centre for Molecular and Biomolecular Informatics/Nijmegen, Centre for Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
J R Soc Interface. 2008 Feb 6;5(19):151-70. doi: 10.1098/rsif.2007.1047.
The gap between the amount of genome information released by genome sequencing projects and our knowledge about the proteins' functions is rapidly increasing. To fill this gap, various 'genomic-context' methods have been proposed that exploit sequenced genomes to predict the functions of the encoded proteins. One class of methods, phylogenetic profiling, predicts protein function by correlating the phylogenetic distribution of genes with that of other genes or phenotypic characteristics. The functions of a number of proteins, including ones of medical relevance, have thus been predicted and subsequently confirmed experimentally. Additionally, various approaches to measure the similarity of phylogenetic profiles and to account for the phylogenetic bias in the data have been proposed. We review the successful applications of phylogenetic profiling and analyse the performance of various profile similarity measures with a set of one microsporidial and 25 fungal genomes. In the fungi, phylogenetic profiling yields high-confidence predictions for the highest and only the highest scoring gene pairs illustrating both the power and the limitations of the approach. Both practical examples and theoretical considerations suggest that in order to get a reliable and specific picture of a protein's function, results from phylogenetic profiling have to be combined with other sources of evidence.
基因组测序项目所公布的基因组信息量与我们对蛋白质功能的了解之间的差距正在迅速扩大。为了填补这一差距，人们提出了各种“基因组上下文”方法，利用已测序的基因组来预测编码蛋白质的功能。其中一类方法，即系统发育谱分析，通过将基因的系统发育分布与其他基因或表型特征的分布相关联来预测蛋白质功能。包括一些具有医学相关性的蛋白质的功能，因此已被预测并随后通过实验得到证实。此外，还提出了各种测量系统发育谱相似性以及考虑数据中系统发育偏差的方法。我们回顾了系统发育谱分析的成功应用，并使用一组微孢子虫基因组和25个真菌基因组分析了各种谱相似性测量方法的性能。在真菌中，系统发育谱分析对得分最高且唯一得分最高的基因对产生了高可信度的预测，这既说明了该方法的强大之处，也说明了其局限性。实际例子和理论思考都表明，为了可靠而具体地了解蛋白质的功能，系统发育谱分析的结果必须与其他证据来源相结合。
