使用功能性重要位置預測直系同源關係

Abstract

準確預測基因功能在蛋白質體的時代扮演著重要的角色。在替未知基因作功能註解時，最可靠的方式是透過其他物種的直系同源基因來萃取功能資訊。我們提出了一個以重要位置為基礎的方法來辨識直系同源關係。本研究在同源基因的多序列排比上找出可以區分不同旁系同源基因的重要位置，並且利用這些位置作為特徵，對於未知基因進行直系同源關係的預測。本研究應用在一個高度探討的桿菌轉錄子家族，LacI family，獲得的重要位置與生物實驗所得到的結果一致，同時只有少數的false positives，因此本研究對於定點突變實驗的設計具有相當的參考價值。另外，我們使用了α-proteasome family, glycoprotein hormone family 以及growth hormone family來驗證本研究對於直系同源基因的預測準確度，並且與其他的親緣分析方法作比較，在這三個家族中，本研究比以往的方法獲得較高的預測準確度，同時具有合理的執行時間。

Making accurate functional predictions for genes plays an important role in the era of proteomics. The most reliable functional information is extracted from orthologs in other species when annotating an unknown gene. Here a site-based approach is proposed to identyfing orthologous relations. The method predicts important sites that confer specificity of paralogs on multiple sequence alignment from orthologous and paralogous proteins and takes advantage of these sites to infer orthologous relation to an unannotated protein. When applied to LacI family, a large family of bacterial transcription factors that is highly studied, the method is able to identify important sites concur with that from biological experimental results with few false positives and hence is helpful to guide experiments such as site-specific mutagenesis. The method is also applied to α-proteasome family, glycoprotein hormone family and growth hormone family to verify the ability of predicting orthologs. Comparing with several phylogenetic analysis tools that are capable of predicting orthologs, our method obtains better predictive accuracy on these three families among all the previous works with reasonable execution time.