Three-dimensional reconstruction of single-cell chromosome structure using recurrence plots

Abstract

Single-cell analysis of the three-dimensional (3D) chromosome structure can reveal cell-to-cell variability in genome activities. Here, we propose to apply recurrence plots, a mathematical method of nonlinear time series analysis, to reconstruct the 3D chromosome structure of a single cell based on information of chromosomal contacts from genome-wide chromosome conformation capture (Hi-C) data. This recurrence plot-based reconstruction (RPR) method enables rapid reconstruction of a unique structure in single cells, even from incomplete Hi-C information.

Inferring diploid 3D chromatin structures from Hi-C data

“…Ensemble models can also be difficult to validate and interpret. "Consensus" approaches, on the other hand, make the assumption that bulk Hi-C data can be accurately summarized in a single, consensus 3D structure [12,9,34,37,2,22,15]. Modeling a single structure tends to be less computationally demanding than modeling an entire population of structures.…”

3D modeling of chromatin structure: is there a way to integrate and reconcile single cell and population experimental data?

“…Those methods diverse in their representation, scoring and sampling of the data. [1], [2], [3], [4], [5], and [6] . Refer to the text for detailed explanation of each strategy.…”

“…(1) Bolzer et al 1 (2) Kalhor et al 14 [2], 14,23,44,45 [3], [46][47][48][49][50] [4], [51][52][53][54][55] [5], 44,56-63 and [6]. 14,23,45,64,65 Refer to the text for detailed explanation of each strategy.…”

“…Lennard -jones Harmonic ( ) 12 [1] as dots, with no physical consistency, [46][47][48][49][50][51][52]55,59,60,63,64 [2] as spheres, 14,16,23,44,45,54,[56][57][58]61,62,65 [3] as spheres with complex physical properties, for example, a soft external surface and a hard core, 14,23 and [4] as sphere of different sizes (either representing different content in nucleotides, or different levels of compaction). 14,45,57 (b) Schematic representation of the application of the three main physical restraints, the excluded volume (U Excl ), the bond restraint (U Bond ) here represented either as a spring that could be modeled by a Lennard-Jones potential or as a harmonic restraint, the bending (U Bend ) that could in this example be modeled explicitly imposing an angle between three particles or by limiting the distance between two nonconsequtive particles (i, i + 2) using a right-truncated harmonic.…”

“…Giorgetti et al23 ; Meluzzi and Arya 44 ; Tjong et al45 (3) Hirata et al46 ; Lesne et al47 ; Paulsen et al48 ; Shavit et al49 ; Zhang et al 50 ; (4) Park and Lin 51 ; Park and Lin 52 ; Parker 53 ; Peng et al 54 ; Zou et al 55 (5) Meluzzi and Arya 44 ; Ay et al 56 ; Baù and Marti-Renom 57 ; Duan et al 58 ; Nowotny et al 59 ; Rousseau et al 60 ; Tokuda et al 61 ; Trieu and Cheng 62 ; Varoquaux et al 63 (6) Kalhor et al 14 ; Giorgetti et al 23 ; Tjong et al 45 ; Hu et al 64 ; Wang et al 65 ; | Modeling strategies. Six main different modeling strategies are currently available for modeling genomes and genomic domains.…”