Plus ça change - evolutionary sequence divergence predicts protein subcellular localization signals.
Plus ça change - evolutionary sequence divergence predicts protein subcellular localization signals.
复制标题
DOI：
10.1186/1471-2164-15-46
复制
发表时间：
2014-01-20
期刊：
影响因子：
4.4
通讯作者：
Horton P
中科院分区：
文献类型：
--
作者：
Fukasawa Y;Leung RK;Tsui SK;Horton P
蛋白质的亚细胞定位是理解细胞生物学的核心问题，并且一直是密集研究的焦点。为了从氨基酸序列预测定位，已经尝试了无数的特征：包括氨基酸组成、序列相似性、某些基序或结构域的存在以及许多其他特征。令人惊讶的是，排序基序的序列保守性尚未被采用，尽管其广泛用于诸如预测转录因子结合位点的任务。在这里，我们把问题转过来，并提出了一个概念证明的想法，缺乏序列保守性可以是一个新的功能定位预测。我们发现，对于酵母，哺乳动物和植物数据集，进化序列的分歧单独具有显着的权力，以确定序列的N-末端排序序列。此外，当在自动定义的直系同源物集上计算时，序列分歧几乎与手工策划的一样有效。不幸的是，当与一些传统的序列特征如氨基酸组成相结合时，序列差异并不一定会提高分类性能。然而，其中序列分歧改变预测的蛋白质的事后分析产生了一些具有非典型（即非MPP切割的）基质靶向信号以及一些错误注释的蛋白质。我们报告的第一个定量研究的结果的有效性的进化序列的分歧作为一个功能的蛋白质亚细胞定位预测。我们表明，发散确实是有用的预测，但它不是微不足道的，以提高整体精度，只是通过添加此功能的经典序列功能。然而，我们认为，序列分歧是一个有前途的功能，并显示轶事的例子，它成功的地方，其他功能失败。
Protein subcellular localization is a central problem in understanding cell biology and has been the focus of intense research. In order to predict localization from amino acid sequence a myriad of features have been tried: including amino acid composition, sequence similarity, the presence of certain motifs or domains, and many others. Surprisingly, sequence conservation of sorting motifs has not yet been employed, despite its extensive use for tasks such as the prediction of transcription factor binding sites. Here, we flip the problem around, and present a proof of concept for the idea that the lack of sequence conservation can be a novel feature for localization prediction. We show that for yeast, mammal and plant datasets, evolutionary sequence divergence alone has significant power to identify sequences with N-terminal sorting sequences. Moreover sequence divergence is nearly as effective when computed on automatically defined ortholog sets as on hand curated ones. Unfortunately, sequence divergence did not necessarily increase classification performance when combined with some traditional sequence features such as amino acid composition. However a post-hoc analysis of the proteins in which sequence divergence changes the prediction yielded some proteins with atypical (i.e. not MPP-cleaved) matrix targeting signals as well as a few misannotations. We report the results of the first quantitative study of the effectiveness of evolutionary sequence divergence as a feature for protein subcellular localization prediction. We show that divergence is indeed useful for prediction, but it is not trivial to improve overall accuracy simply by adding this feature to classical sequence features. Nevertheless we argue that sequence divergence is a promising feature and show anecdotal examples in which it succeeds where other features fail.
登录
查看更多内容
影响因子：
11.4
作者：
Bonn, Florian;Tatsuta, Takashi;Langer, Thomas
通讯作者：
Langer, Thomas
影响因子：
--
作者：
Cherkassky, V
通讯作者：
Cherkassky, V
DOI：
10.1007/978-1-61779-582-4_9
发表时间：
2012-01-01
期刊：
EVOLUTIONARY GENOMICS: STATISICAL AND COMPUTATIONAL METHODS, VOL 1
影响因子：
--
作者：
Altenhoff, Adrian M.;Dessimoz, Christophe
通讯作者：
Dessimoz, Christophe
影响因子：
3.4
作者：
Martinsen L;Johnsen A;Venanzetti F;Bachmann L
通讯作者：
Bachmann L
影响因子：
5.8
作者：
Capra, John A.;Singh, Mona
通讯作者：
Singh, Mona