BackgroundMotivated by the general need to identify and classify species based on molecular evidence, genome comparisons have been proposed that are based on measuring mostly Euclidean distances between Chaos Game Representation (CGR) patterns of genomic DNA sequences.ResultsWe provide, on an extensive dataset and using several different distances, confirmation of the hypothesis that CGR patterns are preserved along a genomic DNA sequence, and are different for DNA sequences originating from genomes of different species. This finding lends support to the theory that CGRs of genomic sequences can act as graphic genomic signatures. In particular, we compare the CGR patterns of over five hundred different 150,000 bp genomic sequences spanning one complete chromosome from each of six organisms, representing all kingdoms of life: H. sapiens (Animalia; chromosome 21), S. cerevisiae (Fungi; chromosome 4), A. thaliana (Plantae; chromosome 1), P. falciparum (Protista; chromosome 14), E. coli (Bacteria - full genome), and P. furiosus (Archaea - full genome). To maximize the diversity within each species, we also analyze the interrelationships within a set of over five hundred 150,000 bp genomic sequences sampled from the entire aforementioned genomes. Lastly, we provide some preliminary evidence of this method’s ability to classify genomic DNA sequences at lower taxonomic levels by comparing sequences sampled from the entire genome of H. sapiens (class Mammalia, order Primates) and of M. musculus (class Mammalia, order Rodentia), for a total length of approximately 174 million basepairs analyzed. We compute pairwise distances between CGRs of these genomic sequences using six different distances, and construct Molecular Distance Maps, which visualize all sequences as points in a two-dimensional or three-dimensional space, to simultaneously display their interrelationships.ConclusionOur analysis confirms, for this dataset, that CGR patterns of DNA sequences from the same genome are in general quantitatively similar, while being different for DNA sequences from genomes of different species. Our assessment of the performance of the six distances analyzed uses three different quality measures and suggests that several distances outperform the Euclidean distance, which has so far been almost exclusively used for such studies.
We propose a computational method to measure and visualize interrelationships among any number of DNA sequences allowing, for example, the examination of hundreds or thousands of complete mitochondrial genomes. An "image distance" is computed for each pair of graphical representations of DNA sequences, and the distances are visualized as a Molecular Distance Map: Each point on the map represents a DNA sequence, and the spatial proximity between any two points reflects the degree of structural similarity between the corresponding sequences. The graphical representation of DNA sequences utilized, Chaos Game Representation (CGR), is genome- and species-specific and can thus act as a genomic signature. Consequently, Molecular Distance Maps could inform species identification, taxonomic classifications and, to a certain extent, evolutionary history. The image distance employed, Structural Dissimilarity Index (DSSIM), implicitly compares the occurrences of oligomers of length up to k (herein k = 9) in DNA sequences. We computed DSSIM distances for more than 5 million pairs of complete mitochondrial genomes, and used Multi-Dimensional Scaling (MDS) to obtain Molecular Distance Maps that visually display the sequence relatedness in various subsets, at different taxonomic levels. This general-purpose method does not require DNA sequence alignment and can thus be used to compare similar or vastly different DNA sequences, genomic or computer-generated, of the same or different lengths. We illustrate potential uses of this approach by applying it to several taxonomic subsets: phylum Vertebrata, (super)kingdom Protista, classes Amphibia-Insecta-Mammalia, class Amphibia, and order Primates. This analysis of an extensive dataset confirms that the oligomer composition of full mtDNA sequences can be a source of taxonomic information. This method also correctly finds the mtDNA sequences most closely related to that of the anatomically modern human (the Neanderthal, the Denisovan, and the chimp), and that the sequence most different from it in this dataset belongs to a cucumber.
BackgroundStudies exploring the potential of Chaos Game Representations (CGR) of genomic sequences to act as “genomic signatures” (to be species- and genome-specific) showed that CGR patterns of nuclear and organellar DNA sequences of the same organism can be very different. While the hypothesis that CGRs of mitochondrial DNA sequences can act as genomic signatures was validated for a snapshot of all sequenced mitochondrial genomes available in the NCBI GenBank sequence database, to our knowledge no such extensive analysis of CGRs of nuclear DNA sequences exists to date.ResultsWe analyzed an extensive dataset, totalling 1.45 gigabase pairs, of nuclear/nucleoid genomic sequences (nDNA) from 42 different organisms, spanning all major kingdoms of life. Our computational experiments indicate that CGR signatures of nDNA of two different origins cannot always be differentiated, especially if they originate from closely-related species such as H. sapiens and P. troglodytes or E. coli and E. fergusonii. To address this issue, we propose the general concept of additive DNA signature of a set (collection) of DNA sequences. One particular instance, the composite DNA signature, combines information from nDNA fragments and organellar (mitochondrial, chloroplast, or plasmid) genomes. We demonstrate that, in this dataset, composite DNA signatures originating from two different organisms can be differentiated in all cases, including those where the use of CGR signatures of nDNA failed or was inconclusive. Another instance, the assembled DNA signature, combines information from many short DNA subfragments (e.g., 100 basepairs) of a given DNA fragment, to produce its signature. We show that an assembled DNA signature has the same distinguishing power as a conventionally computed CGR signature, while using shorter contiguous sequences and potentially less sequence information.ConclusionsOur results suggest that, while CGR signatures of nDNA cannot always play the role of genomic signatures, composite and assembled DNA signatures (separately or in combination) could potentially be used instead. Such additive signatures could be used, e.g., with raw unassembled next-generation sequencing (NGS) read data, when high-quality sequencing data is not available, or to complement information obtained by other methods of species identification or classification.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1157-8) contains supplementary material, which is available to authorized users.
Supplementary data are available at Bioinformatics online.
This paper proposes a discretization technique for a descriptor differential system. The methodology used is both triangular first order hold discretization and zero order hold for the input function. Upper bounds for the error between the continuous and the discrete time solution are produced for both discretization methods and are shown to be better than any other existing method in the literature.
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