Chromosome3D: reconstructing three-dimensional chromosomal structures from Hi-C interaction frequency data using distance geometry simulated annealingReportar como inadecuado

Chromosome3D: reconstructing three-dimensional chromosomal structures from Hi-C interaction frequency data using distance geometry simulated annealing - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Genomics

, 17:886

Human and rodent genomics


BackgroundReconstructing three-dimensional structures of chromosomes is useful for visualizing their shapes in a cell and interpreting their function. In this work, we reconstruct chromosomal structures from Hi-C data by translating contact counts in Hi-C data into Euclidean distances between chromosomal regions and then satisfying these distances using a structure reconstruction method rigorously tested in the field of protein structure determination.

ResultsWe first evaluate the robustness of the overall reconstruction algorithm on noisy simulated data at various levels of noise by comparing with some of the state-of-the-art reconstruction methods. Then, using simulated data, we validate that Spearman’s rank correlation coefficient between pairwise distances in the reconstructed chromosomal structures and the experimental chromosomal contact counts can be used to find optimum conversion rules for transforming interaction frequencies to wish distances. This strategy is then applied to real Hi-C data at chromosome level for optimal transformation of interaction frequencies to wish distances and for ranking and selecting structures. The chromosomal structures reconstructed from a real-world human Hi-C dataset by our method were validated by the known two-compartment feature of the human chromosome organization. We also show that our method is robust with respect to the change of the granularity of Hi-C data, and consistently produces similar structures at different chromosomal resolutions.

ConclusionChromosome3D is a robust method of reconstructing chromosome three-dimensional models using distance restraints obtained from Hi-C interaction frequency data. It is available as a web application and as an open source tool at

KeywordsGenome structure Chromosome structure Three-dimensional modelling Distance geometry Simulated annealing Abbreviations3DThree-dimensional

CNSCrystallography and NMR System

DGSADistance geometry simulated annealing

FISHFluorescence in situ hybridization

IFInteraction frequency

MDSMetric multidimensional scaling

NMDSNon-metric multidimensional scaling

NMRNuclear magnetic resonance

PCCPearson’s correlation coefficient

RMSERoot mean square error

SRCCSpearman’s rank correlation coefficient

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-016-3210-4 contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Badri Adhikari - Tuan Trieu - Jianlin Cheng


Documentos relacionados