Zhou Pei-Yuan, Lee En-Shiun Annie, Sze-To Antonio, Wong Andrew K C
VaryWave Technology Co., Ltd., 538A, Core Building 2, Hong Kong Science Park, Shatin, NT, Hong Kong.
VerticalScope Inc., 111 Peter Street, Suite 900, Toronto, ON M5V 2H1, Canada.
Proteomes. 2018 Feb 8;6(1):10. doi: 10.3390/proteomes6010010.
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 (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 (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.
一个蛋白质家族具有相似且多样的功能，这些功能作为比对序列片段在局部是保守的。进一步发现它们的关联模式可以揭示微妙的家族亚组特征。由于比对模式簇（APC）中的比对残基关联（ARA）因功能、因素和源环境中的差异而复杂且相互交织，我们最近开发了一种新方法：比对残基关联发现与解缠（ARADD）来解决这个问题。ARADD首先从一个APC中获取一个ARA频率矩阵，并将其转换为一个调整后的序列残基向量（SRV）。然后它将SRV解缠为主成分（PC），并将它们的向量重新投影到一个SRV上，以揭示简洁的正交AR组。在本研究中，我们将ARADD应用于A类清道夫受体（SR-A），这是一个多样的蛋白质家族的一个亚类，它与具有多种未明确知晓的生物学功能的修饰脂蛋白结合。我们的实验结果表明，ARADD可以揭示具有多样功能和高度可变序列长度的序列片段中的微妙亚组。我们还证明，在位置权重矩阵或APC中捕获的ARA在生物学功能和结构域位置上是相互纠缠的，但通过ARADD解缠后可以揭示不同的亚类，而无需知道它们的实际出现位置。
