基于Lorentzian目标函数的三维基因组结构建模

Tuan Trieu, Jianlin Cheng
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引用次数: 23

摘要

利用染色体构象捕获数据(如Hi-C数据)重建基因组的三维结构是近年来生物信息学和计算生物学中的一个重要问题。在这次演讲中,我将介绍我们最新的方法,使用洛伦兹函数来描述染色体区域之间的距离限制,这将用于指导单个染色体和整个基因组的三维结构的重建。与传统的误差平方函数和高斯概率函数等目标函数相比,该方法对来自Hi-C数据的噪声距离约束具有更好的鲁棒性。该方法可以有效地处理染色体内和染色体间的接触,以构建由许多染色体组成的人类基因组等大基因组的三维结构,这是大多数现有方法无法实现的。我们已经在GitHub (https://github.com/BDM-Lab/LorDG)上发布了实现该方法(称为LorDG)的Java源代码,社区正在使用它来建模3D基因组结构。我们目前正在进一步改进该方法,以建立非常高分辨率(例如1KB碱基对)的3D基因组和染色体模型。
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3D Genome Structure Modeling by Lorentzian Objective Function
Reconstructing 3D structure of a genome from chromosomal conformation capturing data such as Hi-C data has emerged as an important problem in bioinformatics and computational biology in the recent years. In this talk, I will present our latest method that uses Lorentzian function to describe distance restraints between chromosomal regions, which will be used to guide the reconstruction of 3D structures of individual chromosomes and an entire genome. The method is more robust against noisy distance restraints derived from Hi-C data than traditional objective functions such as squared error function and Gaussian probabilistic function. The method can handle both intra- and inter-chromosomal contacts effectively to build 3D structures of a big genome such as the human genome consisting of a number of chromosomes, which are not possible with most existing methods. We have released the Java source code that implements the method (called LorDG) at GitHub (https://github.com/BDM-Lab/LorDG), which is being used by the community to model 3D genome structures. We are currently further improving the method to build very high-resolution (e.g. 1KB base pair) 3D genome and chromosome models.
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