UT-ORNL Graduate School of Genome Science and Technology, Knoxville, Tennessee 37996, USA.
Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee 37996, USA.
Phys Rev E. 2020 Jan;101(1-1):012419. doi: 10.1103/PhysRevE.101.012419.
As a unique subset of functional polymers, many biopolymers have a set of well-defined three-dimensional (3D) structural characteristics that can be described by spatial contacts between monomers. Statistical analysis of the contacts has been extremely productive in characterizing the biopolymer structural ensemble, such as for 3D chromosome structures. Often, native contacts and compartment structures are the focus of the studies, while the generic polymer aspect, such as the overall decaying of contacts with increasing sequence distance, is analyzed separately or preemptively removed. Here, we explore insights that can be gained by performing "compartment analysis" that keeps the distance decay, which we believe is particularly useful for characterizing the structure transformation of biopolymers. We tested contact analysis on several such transformations under physical perturbation or biological processes, including (1) unfolding of proteins induced by thermal denaturation, (2) chromosome conformation transition during the cell cycle, and (3) chromosome unpacking by physicochemical perturbations. Useful score functions were developed to further quantitatively characterize the transformation judging from the contact analysis. We also find that the sinusoidal undertone of eigenvector patterns (the "unwanted," low frequency signal, in contrast to the detailed A/B compartment) that had previously been attributed to biological effects of centromere proximal and distal interactions may in fact reflect a universal feature of polymers that have relatively weaker long-range contacts.
作为功能高分子的一个独特子集，许多生物聚合物具有一组定义明确的三维（3D）结构特征，这些特征可以通过单体之间的空间接触来描述。对接触进行统计分析在描述生物聚合物结构整体方面非常有效，例如 3D 染色体结构。通常，天然接触和隔室结构是研究的重点，而通用聚合物方面，例如随着序列距离的增加接触逐渐衰减，则分别进行分析或预先去除。在这里，我们通过执行“隔室分析”来探索可以获得的见解，这种分析保留了距离衰减，我们认为这对于描述生物聚合物的结构转变特别有用。我们在物理扰动或生物过程下的几种这样的转变中测试了接触分析，包括（1）热变性诱导的蛋白质展开，（2）细胞周期中染色体构象的转变，以及（3）物理化学扰动引起的染色体解包。从接触分析出发，我们开发了有用的评分函数来进一步定量地描述转变。我们还发现，先前归因于着丝粒近端和远端相互作用的生物效应的特征向量模式的正弦底色（与详细的 A/B 隔室相比，是“不需要的”低频信号）实际上可能反映了具有相对较弱长程接触的聚合物的普遍特征。
