title: Additive methods for genomic signatures.
abstract: BACKGROUND
  Studies 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Computer Science, University of Western Ontario, London ON, N6A 5B7, Canada.
authors.forename: Rallis
authors.initials: R
authors.lastname: Karamichalis
authors.affiliation: School of Computing Science, University of Waterloo, Waterloo, ON, N2L 3G1, Canada. lila.kari@uwaterloo.ca.|Department of Computer Science, University of Western Ontario, London ON, N6A 5B7, Canada. lila.kari@uwaterloo.ca.
authors.forename: Lila
authors.initials: L
authors.lastname: Kari
authors.affiliation: Department of Mathematics and Computing Science, Saint Mary's University, Halifax NS, Canada.
authors.forename: Stavros
authors.initials: S
authors.lastname: Konstantinidis
authors.affiliation: Department of Computer Science, University of Western Ontario, London ON, N6A 5B7, Canada.|Department of Mathematics and Computing Science, Saint Mary's University, Halifax NS, Canada.
authors.forename: Steffen
authors.initials: S
authors.lastname: Kopecki
authors.affiliation: Department of Computer Science, University of Western Ontario, London ON, N6A 5B7, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Solis-Reyes
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans
chemical_list: D004269:DNA, Bacterial; D004272:DNA, Mitochondrial
keywords: Additive DNA signature; Alignment-free; Assembled DNA signature; Chaos Game Representation; Comparative genomics; Composite DNA signature; Genomic signature; Information distance