Numerical Characterization of DNA Sequences for Alignment-free Sequence Comparison – A Review

Background: Biological macromolecules namely, DNA, RNA, and protein have their building blocks organized in a particular sequence and the sequential arrangement encodes evolutionary history of the organism (species). Hence, biological sequences have been used for studying evolutionary relationships among the species. This is usually carried out by multiple sequence algorithms (MSA). Due to certain limitations of MSA, alignment-free sequence comparison methods were developed. The present review is on alignment-free sequence comparison methods carried out using numerical characterization of DNA sequences. Discussion: The graphical representation of DNA sequences by chaos game representation and other 2-dimesnional and 3-dimensional methods are discussed. The evolution of numerical characterization from the various graphical representations and the application of the DNA invariants thus computed in phylogenetic analysis is presented. The extension of computing molecular descriptors in chemometrics to the calculation of new set of DNA invariants and their use in alignment-free sequence comparison in a N-dimensional space and construction of phylogenetic tress is also reviewed. Conclusion: The phylogenetic tress constructed by the alignment-free sequence comparison methods using DNA invariants were found to be better than those constructed using alignment-based tools such as PHLYIP and ClustalW. One of the graphical representation methods is now extended to study viral sequences of infectious diseases for the identification of conserved regions to design peptide-based vaccine by combining numerical characterization and graphical representation.

Microbial Diversity Based on Multifractal Analysis of Metagenomes

Species diversity in microbiome is a cutting-edge concept in metagenomic research. In this study, we propose a multifractal analysis for metagenomic research. From the chaos game representation (CGR) visualization of simulated and real metagenomes, we find that there exists self-similarity in the visualization of metagenomes. Then we compute the multifractal dimensions for simulated and real metagenomes. For simulated metagenomes, we also compute their diversity indices, such as species richness indices, Shannon’s diversity indices and Simpson’s diversity indices respectively for varying value of . Fom the Pearson correlation coefficients between their multifractal dimensions and traditional species diversity indices, we find that the correlation coefficients between the multifractal dimensions and species richness indices and Shannon diversity indices reach their maximums at respectively. The correlation coefficients between the multifractal dimensions and Simpson’s diversity indices reach their maximums at nearly. So the traditional diversity indices can be unified by the frame of multifractal analysis. These results coincided with the similar results in macrobial ecology. Finally, we apply our methods to real metagenomes of 100 infants’ gut microbiomes when they are newborn, 4 months and 12 months. Our results show that multifractal dimensions of infants’ gut microbiomes can discriminate the age difference.

Involving FCGR images in studying fractality and multifractality in human chromosome 22 and bacteria complete genome

The frequency chaos game representation (FCGR) is a simple yet powerful visualization method of DNA sequences. It provides the possibility of representing genomes by images, revealing in such a way different fractal structures. In this paper, we perform a fractal and multifractal analysis of Human chromosome 22 and some complete genomes based on the FGCR image. We used the fractal dimension (FD) and the multifractality degree (ΔDq) to characterize and distinguish genomes. First, we construct the FCGR image with different orders of human chromosome 22. Next, we calculate the fractal dimension, the general dimension spectrum and the multifractal spectrum of each FCGR image using the box-counting method. Then, we examine the FCGR image fractal and multifractal characteristics impact on highlighting the existence of repetitive DNA sequences in human chromosome 22. We also observe the relationship between fractality and multifractality. After that, we apply this study to bacteria completes genomes and C.elegans chromosome I. The obtained results show that the multifractal spectra of all organisms studied are multifractal-like and chromosome 22 strong multifractality proves its richness of repetitive sequences. Also, we observed that with the increasing the FCGR order value, the multifractality grows and the fractal dimension lessens. Finally, by assigning to each sequence a point in two-dimensional space (FD, ΔDq), we obtained three classes of genomes. We can easily distinguish the human chromosome 22 from other genomes and Bacteria are almost close in the spaces (FD, ΔDq).