Revealing Subtle Functional Subgroups in Class A Scavenger Receptors by Pattern Discovery and Disentanglement of Aligned Pattern Clusters.
Revealing Subtle Functional Subgroups in Class A Scavenger Receptors by Pattern Discovery and Disentanglement of Aligned Pattern Clusters.
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DOI：
10.3390/proteomes6010010
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发表时间：
2018-02-08
期刊：
影响因子：
3.3
通讯作者：
Wong AKC
中科院分区：
文献类型：
--
作者：
Zhou PY;Lee EA;Sze-To A;Wong AKC
蛋白质家族具有相似和不同的功能，作为比对的序列片段在局部保守。进一步发现它们的关联模式可能会揭示出微妙的家族亚群特征。由于源环境中纠缠功能、因素和方差的影响，对齐模式簇(APC)中的对齐残基关联(ARA)是复杂和相互交织的，我们最近开发了一种新的方法：对齐残基关联发现和解缠(ARADD)来解决这一问题。ARADD首先从APC获得ARA频率矩阵，并将其转换为调整后的统计残差向量空间(SRV)。然后，它将SRV分解成主成分(PC)，并将它们的向量重新投影到SRV，以显示简洁的正交AR群。在这项研究中，我们将ARADD应用于A类清道夫受体(SR-A)，这是一个与修饰的脂蛋白结合的不同蛋白质家族的一个亚类，其不同的生物学功能尚不清楚。我们的实验结果表明，ARADD可以揭示具有不同功能和高度可变的序列长度的序列片段中的细微亚群。我们还证明了在位置权重矩阵或APC中捕获的aras在生物功能和结构域位置上是纠缠的，但通过ARADD解缠揭示了不同的亚类，而不知道它们的实际出现位置。
A protein family has similar and diverse functions locally conserved as aligned sequence segments. Further discovering their association patterns could reveal subtle family subgroup characteristics. Since aligned residues associations (ARAs) in Aligned Pattern Clusters (APCs) are complex and intertwined due to entangled function, factors, and variance in the source environment, we have recently developed a novel method: Aligned Residue Association Discovery and Disentanglement (ARADD) to solve this problem. ARADD first obtains from an APC an ARA Frequency Matrix and converts it to an adjusted statistical residual vector space (SRV). It then disentangles the SRV into Principal Components (PCs) and Re-projects their vectors to a SRV to reveal succinct orthogonal AR groups. In this study, we applied ARADD to class A scavenger receptors (SR-A), a subclass of a diverse protein family binding to modified lipoproteins with diverse biological functionalities not explicitly known. Our experimental results demonstrated that ARADD can unveil subtle subgroups in sequence segments with diverse functionality and highly variable sequence lengths. We also demonstrated that the ARAs captured in a Position Weight Matrix or an APC were entangled in biological function and domain location but disentangled by ARADD to reveal different subclasses without knowing their actual occurrence positions.