Exhaustive assignment of compositional bias reveals universally prevalent biased regions: analysis of functional associations in human and Drosophila.
Exhaustive assignment of compositional bias reveals universally prevalent biased regions: analysis of functional associations in human and Drosophila.
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组成偏见的详尽分配揭示了普遍普遍的偏见区域：人类和果蝇中功能关联的分析。
DOI：
10.1186/1471-2105-7-441
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发表时间：
2006-10-10
影响因子：
3
通讯作者：
Harrison PM
中科院分区：
文献类型：
--
作者：
Harrison PM
组成偏向（CB）区域是蛋白质序列中主要由不同的氨基酸残基子集组成的延伸;这些区域通常与细胞中的结构作用或蛋白质紊乱有关。我们推导出一个程序的CB区域的详尽的分配和分类，并已将其应用到13后生动物蛋白质组。首先扫描序列以寻找单一氨基酸类型的最低概率重复序列（LPS）;随后，迭代地对多个残基类型的最低概率重复序列（LPS）进行穷举搜索，直到收敛，以定义CB区域边界。我们分析了具有> 2000万个残基的> 40，000个CB区域;引人注目的是，9个单/双残基偏差普遍存在，并且在脊椎动物和无脊椎动物中始终排名很高。在人和D.我们分析了CB区域的长度、保守性，推断功能类别并预测蛋白质紊乱，并过滤卷曲螺旋和蛋白质结构。特别是，我们发现，一些普遍丰富的CB区域有显着的协会在人类和果蝇的转录和核定位，也被预测为中度或高度紊乱。聚焦于基于Q的偏置区域，我们发现这些区域通常仅在哺乳动物中很好地保守（出现在60-80%的直系同源物中），而较短的人类转录相关CB区域在哺乳动物之外不保守;它们也优先与蛋白质结构域（例如同源结构域和糖皮质激素受体DNA结合结构域）连接。一般来说，在这些人类和果蝇CB区域中只有~40-50%的残基预测蛋白质紊乱。这些数据可用于基因的进一步功能表征和结构基因组学倡议。
Compositionally biased (CB) regions are stretches in protein sequences made from mainly a distinct subset of amino acid residues; such regions are frequently associated with a structural role in the cell, or with protein disorder. We derived a procedure for the exhaustive assignment and classification of CB regions, and have applied it to thirteen metazoan proteomes. Sequences are initially scanned for the lowest-probability subsequences (LPSs) for single amino-acid types; subsequently, an exhaustive search for lowest probability subsequences (LPSs) for multiple residue types is performed iteratively until convergence, to define CB region boundaries. We analysed > 40,000 CB regions with > 20 million residues; strikingly, nine single-/double- residue biases are universally abundant, and are consistently highly ranked across both vertebrates and invertebrates. To home in subpopulations of CB regions of interest in human and D. melanogaster, we analysed CB region lengths, conservation, inferred functional categories and predicted protein disorder, and filtered for coiled coils and protein structures. In particular, we found that some of the universally abundant CB regions have significant associations to transcription and nuclear localization in Human and Drosophila, and are also predicted to be moderately or highly disordered. Focussing on Q-based biased regions, we found that these regions are typically only well conserved within mammals (appearing in 60–80% of orthologs), with shorter human transcription-related CB regions being unconserved outside of mammals; they are also preferentially linked to protein domains such as the homeodomain and glucocorticoid-receptor DNA-binding domain. In general, only ~40–50% of residues in these human and Drosophila CB regions have predicted protein disorder. This data is of use for the further functional characterization of genes, and for structural genomics initiatives.
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DOI：
10.1002/prot.10437
发表时间：
2003-09-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Vucetic, S;Brown, CJ;Obradovic, Z
通讯作者：
Obradovic, Z
影响因子：
14.9
作者：
Harris, MA;Clark, J;White, R
通讯作者：
White, R
影响因子：
8
作者：
Wolf, E;Kim, PS;Berger, B
通讯作者：
Berger, B
影响因子：
5.6
作者：
Ward, JJ;Sodhi, JS;Jones, DT
通讯作者：
Jones, DT
影响因子：
12.3
作者：
Harrison, PM;Gerstein, M
通讯作者：
Gerstein, M