Manifold Based Optimization for Single-Cell 3D Genome Reconstruction
Manifold Based Optimization for Single-Cell 3D Genome Reconstruction
复制标题
DOI：
10.1371/journal.pcbi.1004396
复制
发表时间：
2015-08-01
影响因子：
4.3
通讯作者：
Collas, Philippe
中科院分区：
文献类型：
--
作者：
Paulsen, Jonas;Gramstad, Odin;Collas, Philippe
基因组的三维（3D）结构对于基因表达和细胞分化的协调是重要的。虽然3D基因组定位长期以来一直难以实现，但最近将高通量测序技术应用于染色体构象捕获（3C）技术，首次实现了全基因组结构表征。然而，从基于3C的数据重建“共有”3D基因组是一个具有挑战性的问题，因为数据是在数百万个细胞上聚合的。然而，最近的单细胞适应3C技术，允许非聚集的基因组结构的结构评估，但数据遭受稀疏和嘈杂的相互作用采样。我们提出了一种基于流形优化（MBO）的方法，用于从染色体接触数据重建3D基因组结构。我们表明，MBO是能够重建的染色体接触的基础上的三维结构，实施较少的结构违规比可比的方法。此外，MBO适用于大型系统的高效高通量重建，例如整个基因组，允许跨细胞系和不同物种的基因组结构的比较研究。
The three-dimensional (3D) structure of the genome is important for orchestration of gene expression and cell differentiation. While mapping genomes in 3D has for a long time been elusive, recent adaptations of high-throughput sequencing to chromosome conformation capture (3C) techniques, allows for genome-wide structural characterization for the first time. However, reconstruction of "consensus" 3D genomes from 3C-based data is a challenging problem, since the data are aggregated over millions of cells. Recent single-cell adaptations to the 3C-technique, however, allow for non-aggregated structural assessment of genome structure, but data suffer from sparse and noisy interaction sampling. We present a manifold based optimization (MBO) approach for the reconstruction of 3D genome structure from chromosomal contact data. We show that MBO is able to reconstruct 3D structures based on the chromosomal contacts, imposing fewer structural violations than comparable methods. Additionally, MBO is suitable for efficient high-throughput reconstruction of large systems, such as entire genomes, allowing for comparative studies of genomic structure across cell-lines and different species.