Algorithm And Web-Service On The Chromatin 3D Structure Reconstruction Based On Hi-C Data

The three-dimensional structure of chromatin plays an important role in the regulation of gene expression,cell development,and the occurrence of genetic diseases.With the advent of chromatin conformation capture technology and its derivatives,especially the emergence of Hi-C technology that captures chromatin interactions across the whole genome,a large number of chromatin interaction frequency datasets are now available.How to use these data to reconstruct the three-dimensional conformation of chromatin has become an important research direction in the field of three-dimensional genomics.The existing reconstruction algorithms are mainly divided into two categories: thermodynamics-based method and distance-restraint-based method.The application of these reconstruction methods helps to reveal the formation mechanism of chromatin structure and its biological function.In this paper,a new reconstruction algorithm based on co-clustering coefficient and error vector resultant,named EVRC algorithm,is proposed.Firstly,the co-clustering coefficient between chromatin fragments was calculated,and then the error vectors of each fragment were summed,respectively.The three-dimensional structure of chromatin was reconstructed through continuous iterative optimization.To evaluate the validity and accuracy of the algorithm,we apply it to the simulation datasets of six typical structures and the real Hi-C datasets.When the six simulated structures from simple to complex were reconstructed under different transformation parameters and random noises,the results showed that there are always high similarities between reconstructed structures and real structures,which indicates the effectiveness and robustness of the EVRC algorithm.When applied to the real Hi-C data,we first performed three-dimensional reconstruction for the five chromosomes wild-type Arabidopsis thaliana at different resolutions.The results showed differences in structural features between chromosomes.When reconstructing chromosome 1 of wild-type and AtMORC6 mutant Arabidopsis thaliana,the EVRC algorithm accurately displayed the conformational change of the centromere region.This illustrates the applicability and accuracy of the EVRC algorithm in multi-chromosomal structural reconstruction of eukaryotic organisms.For ease of use,we also developed a website to provide online services.As a new tool for chromatin 3D structural reconstruction,the EVRC algorithm will promote the studies on chromatin structure and function.