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2016 ; 17
(1
): 886
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Chromosome3D: reconstructing three-dimensional chromosomal structures from Hi-C
interaction frequency data using distance geometry simulated annealing
#MMPMID27821047
Adhikari B
; Trieu T
; Cheng J
BMC Genomics
2016[Nov]; 17
(1
): 886
PMID27821047
show ga
BACKGROUND: Reconstructing 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. RESULTS: We 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. CONCLUSION: Chromosome3D 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
http://sysbio.rnet.missouri.edu/chromosome3d/ .