RT Journal Article
SR Electronic
T1 Flexibility and rigidity index for chromosome packing, flexibility and dynamics analysis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 374132
DO 10.1101/374132
A1 Jiajie Peng
A1 Jinjin Yang
A1 Kelin Xia
YR 2018
UL http://biorxiv.org/content/early/2018/07/22/374132.abstract
AB Motivation The packing of genomic DNA from double string into highly-order hierarchial assemblies has great impact on chromosome flexibility, dynamics and functions. The open and accessible regions of chromosome are the primary binding positions for regulatory elements and are crucial to nuclear processes and biological functions.Results Motivated by the success of flexibility-rigidity index (FRI) in biomolecular flexibility analysis and drug design, we propose a FRI based model for quantitatively characterizing the chromosome flexibility. Based on the Hi-C data, a flexibility index for each locus can be evaluated. Physically, the flexibility is tightly related to the packing density. Highly compacted regions are usually more rigid, while loosely packed regions are more flexible. Indeed, a strong correlation is found between our flexibility index and DNase and ATAC values, which are measurements for chromosome accessibility. Recently, Gaussian network model (GNM) is applied to analyze the chromosome accessibility and a mobility profile has been proposed to characterize the chromosome flexibility. Compared with GNM, our FRI is slightly more accurate (1% to 2% increase) and significantly more efficient in both computational time and costs. For a 5kb resolution Hi-C data, the flexibility evaluation process only takes FRI a few minutes on a single-core processor. In contrast, GNM requires 1.5 hours on 10 CPUs. Moreover, interchromosome information can be easily incorporated into the flexibility evaluation, thus further enhance the accuracy of our FRI. In contrast, the consideration of interchromosome information into GNM will significantly increase the size of its Laplacian matrix, thus computationally extremely challenging for the current GNM.Availability The software is available at https://github.com/jiajiepeng/FRI_chrFle.Contact xiakelin{at}ntu.edu.sg; jiajiepeng{at}nwpu.edu.cn