论文标题
从HI-C接触地图到三维人类染色体的三维组织
From Hi-C Contact Map to Three-dimensional Organization of Interphase Human Chromosomes
论文作者
论文摘要
可以使用染色体构象捕获（3C）方法和相关的HI-C实验来推断两个基因座的概率，被特定的基因组长度分开，接触。如何从触点图（列出了大量基因座之间的平均接触概率，到三维结构的合奏之间）的矩阵是一个开放的问题。解决此问题的解决方案而不假设假定的能量函数将是理解大自然解决紧密细胞空间中染色体的包装方式的第一步。我们基于染色体的聚合物物理特征和最大熵原理（称为hipps（HI-C-Polymer-physys-structures）方法）创建了一个理论，该理论使我们能够仅根据HI-C接触图计算3D结构。我们使用测量的接触图作为输入创建了来自淋巴细胞细胞的23个染色体的3D结构集合。嬉皮方法表明，即使在单个细胞类型中，染色体的构象也是异质的。在不同的细胞类型（正常和癌细胞）中，同一染色体的构象异质性的差异也可以使用我们的理论进行定量识别。我们通过表明预测3D结构的23个染色体的计算体积与实验估计值吻合，从而验证了该方法。因为该方法是一般的，所以任何物种的3D结构都可以直接从触点图中计算出，而无需按照通常的方式假设特定的聚合物模型。
The probability of two loci, separated by a certain genome length, being in contact can be inferred using the Chromosome Conformation Capture (3C) method and related Hi-C experiments. How to go from the contact map, a matrix listing the mean contact probabilities between a large number of pairs of loci, to an ensemble of three-dimensional structures is an open problem. A solution to this problem, without assuming an assumed energy function, would be the first step in understanding the way nature has solved the packaging of chromosomes in tight cellular spaces. We created a theory, based on polymer physics characteristics of chromosomes and the maximum entropy principles, referred to as HIPPS (Hi-C-Polymer-Physics-Structures) method, that allows us to calculate the 3D structures solely from Hi-C contact maps. We created an ensemble of 3D structures for the 23 chromosomes from lymphoblastoid cells using the measured contact maps as inputs. The HIPPS method shows that conformations of chromosomes are heterogeneous even in a single cell type. The differences in the conformational heterogeneity of the same chromosome in different cell types (normal as well as cancerous cells) can also be quantitatively discerned using our theory. We validate the method by showing that the calculated volumes of the 23 chromosomes from the predicted 3D structures are in good agreement with experimental estimates. Because the method is general, the 3D structures for any species may be calculated directly from the contact map without the need to assume a specific polymer model, as is customarily done.
