Wavelet-based method to disentangle transcription-and replication-associated strand asymmetries in mammalian genomes

in Applied & Computational Harmonic Analysis (2010), 28

During genome evolution, the two strands of the DNA double helix are not subjected to the same mutation patterns. This mutation bias is considered as a by-product of replicative and transcriptional ... [more ▼]

During genome evolution, the two strands of the DNA double helix are not subjected to the same mutation patterns. This mutation bias is considered as a by-product of replicative and transcriptional activities. In this paper, we develop a wavelet-based methodology to analyze the DNA strand asymmetry profiles with the specific goal to extract the contributions associated with replication and transcription respectively. In a first step, we use an adapted N-shaped analyzing wavelet to perform a multi-scale pattern recognition analysis of the sum of the TA and GC skews along human chromosomes. This method provides an 1 Mbp characteristic objective segmentation of the human genome in skew domains of size, bordered by two putative replication origins recognized as large amplitude upward jumps in the noisy skew profile. In a second step, we use a least-square fitting procedure to disentangle, in these skew domains, the small-scale (the mean human gene size 30 kbp) square-like transcription component from the global N-shaped component induced by replication. When applying this procedure to the 22 human autosomes, we delineate 678 replication domains of mean length L = 1.2 ± 0.6 Mbp spanning 33.8% of the human genome and we predict 1062 replication origins. When investigating the distribution of transcription-associated skew inside the replication N-domains, we reveal some dependence upon the distance to the putative replication origins located at N- domain extremities, the closer the genes to the origin, the larger their transcription bias as the signature of a higher transcriptional activity in the germ-line. As a comparative analysis, we further apply our wavelet-based methodology to skew profiles along the mouse chromosomes. The striking similarity of the results in human and mouse indicates that the remarkable gene organization observed inside the human replication N-domains is likely to be a general feature of mammalian genomes. [less ▲]

DNA replication timing data corroborate in silico human replication origin predictions

in Physical Review Letters (2007), 99

We develop a wavelet-based multiscale pattern recognition methodology to disentangle the replication- from the transcription-associated compositional strand asymmetries observed in the human genome ... [more ▼]

We develop a wavelet-based multiscale pattern recognition methodology to disentangle the replication- from the transcription-associated compositional strand asymmetries observed in the human genome. Comparing replication skew profiles to recent high-resolution replication timing data reveals that most of the putative replication origins that border the so-identified replication domains are replicated earlier than their surroundings whereas the central regions replicate late in the S phase. We discuss the implications of this first experimental confirmation of these replication origin predictions that are likely to be early replicating and active in most tissues. [less ▲]