Large-scale chromosome folding versus genomic DNA sequences: A discrete double Fourier transform technique

TL;DR

This paper introduces a novel discrete double Fourier transform (DDFT) technique to analyze large-scale chromosome folding directly from genomic DNA sequences, bridging the gap between structural data and sequence information.

Contribution

The paper presents an original DDFT method capable of detecting hierarchical genome regularities from DNA sequences and physico-chemical parameters, applicable across different organisms.

Findings

DDFT successfully identified chromosome domains in E. coli K-12.

The method correlated well with experimentally established genome units.

DDFT demonstrated versatility on bacteriophage and bacterial genomes.

Abstract

Using state-of-the-art techniques combining imaging methods and high-throughput genomic mapping tools leaded to the significant progress in detailing chromosome architecture of various organisms. However, a gap still remains between the rapidly growing structural data on the chromosome folding and the large-scale genome organization. Could a part of information on the chromosome folding be obtained directly from underlying genomic DNA sequences abundantly stored in the databanks? To answer this question, we developed an original discrete double Fourier transform (DDFT). DDFT serves for the detection of large-scale genome regularities associated with domains/units at the different levels of hierarchical chromosome folding. The method is versatile and can be applied to both genomic DNA sequences and corresponding physico-chemical parameters such as base-pairing free energy. The latter characteristic is closely related to the replication and transcription and can also be used for the assessment of temperature or supercoiling effects on the chromosome folding. We tested the method on the genome of Escherichia coli K-12 and found good correspondence with the annotated domains/units established experimentally. As a brief illustration of further abilities of DDFT, the study of large-scale genome organization for bacteriophage PHIX174 and bacterium Caulobacter crescentus was also added. The combined experimental, modeling, and bioinformatic DDFT analysis should yield more complete knowledge on the chromosome architecture and genome organization.