GenomeFingerprinter and universal genome fingerprint analysis for systematic comparative genomics

How to compare whole genome sequences at large scale has not been achieved via conventional methods based on pair-wisely base-to-base comparison; nevertheless, no attention was paid to handle in-one-sitting a number of genomes crossing genetic category (chromosome, plasmid, and phage) with farther divergences (much less or no homologous) over large size ranges (from Kbp to Mbp). We created a new method, GenomeFingerprinter, to unambiguously produce three-dimensional coordinates from a sequence, followed by one three-dimensional plot and six two-dimensional trajectory projections to illustrate whole genome fingerprints. We further developed a set of concepts and tools and thereby established a new method, universal genome fingerprint analysis. We demonstrated their applications through case studies on over a hundred of genome sequences. Particularly, we defined the total genetic component configuration (TGCC) (i.e., chromosome, plasmid, and phage) for describing a strain as a system, and the universal genome fingerprint map (UGFM) of TGCC for differentiating a strain as a universal system, as well as the systematic comparative genomics (SCG) for comparing in-one-sitting a number of genomes crossing genetic category in diverse strains. By using UGFM, UGFM-TGCC, and UGFM-TGCC-SCG, we compared a number of genome sequences with farther divergences (chromosome, plasmid, and phage; bacterium, archaeal bacterium, and virus) over large size ranges (6Kbp~5Mbp), giving new insights into critical problematic issues in microbial genomics in the post-genomic era. This paper provided a new method for rapidly computing, geometrically visualizing, and intuitively comparing genome sequences at fingerprint level, and hence established a new method of universal genome fingerprint analysis for systematic comparative genomics.Comment: 63 pages, 15 figures, 5 table

Features of genome sequences from bacteria and archaeal bacteria.

<p>Features of genome sequences from bacteria and archaeal bacteria.</p

Features of genome sequences from phages and viruses.

<p>Features of genome sequences from phages and viruses.</p

The UGFM-TGCC-SCG of four archaeal bacterial strains crossing four genera of halophilic Archaea.

<p>One set (A <i>vs</i>.B): <i>Halorubrum lacusprofundii</i> ATCC49239 [chromosome I (NC_012029), chromosome II (NC_012028), plasmid pHLAC01 (NC_012030)] <i>vs</i>. <i>Haloarcula marismortui</i> ATCC43049 [chromosome I (NC_006396), chromosome II (NC_006397), and seven plasmids pNG100 (NC_006389), pNG200 (NC_006390), pNG300 (NC_006391), pNG400 (NC_006392), pNG500 (NC_006393), pNG600 (NC_006394), pNG700 (NC_006395)] focusing on plasmids (A) and as a universal system (B); The other set (C <i>vs</i>.D): <i>Haloferax vocanii</i> DS2 [chromosome (NC_013967), and four plasmids pHV3 (NC_013964), pHV2 (NC_013965), pHV4 (NC_013966), pHV1 (NC_013968)] <i>vs</i>. <i>Halomicrobium mukohataei</i> DSM 12286 [chromosome (NC_013202), plasmid pHmuk01(NC_013201)] focusing on plasmids (C) and as a universal system (D). Note that the tiny spots and the giant visions are elegantly plotted in-one-sitting within the same figure.</p

The primary genome fingerprint map (P-GFM) for the overall comparison among a number of genome fingerprint maps.

<p>(A). Similar: <i>Sulfolobus islandicus</i> M.14.25 (NC_012588) and M.16.4 (NC_012726); (B). Partly similar: <i>S. islandicus</i> Y.N.15.51 (NC_012623) and <i>Methanococcus voltae</i> A3 (NC_014222); (C). Different: <i>S. islandicus</i> Y.G.57.14 (NC_012622) and <i>Methanosphaera stadtmanae</i> 3091 (NC_007681); (D). Mixture: (twelve fragmental genomes of strains in <i>Escherichia coli</i> (listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077912#pone-0077912-t001" target="_blank">Table 1</a>): 91.1.1, 91.1.61, 91.6.59, 913.1.77, 913.5.57, 4431.1.70, 7946.4.7, 10473.1.74, 10473.4.57, 10498.4.86, 12947.1.50, 13941.2.60.</p

The conceptual framework of the universal genome fingerprint analysis (UGFA).

<p>The core concepts and tools include UGFM, UGFM-TGCC, and UGFM-TGCC-SCG. Abbreviations: 3D-P: three-dimensional plot; 2D-TP: two-dimensional trajectory projections; GF: genome fingerprint; GFM: genome fingerprint map; P-GFM: primary genome fingerprint map; S-GFM: secondary genome fingerprint map; UGFM: universal genome fingerprint map; TGCC: total genetic component configuration; UGFM-TGCC: universal genome fingerprint map of total genetic component configuration; SCG: systematic comparative genomics; UGFM-TGCC-SCG: universal genome fingerprint map of total genetic component configuration based systematic comparative genomics; UGFA: universal genome fingerprint analysis.</p

The universal genome fingerprint map (UGFM) for the comparison among a set of genomes in-one-sitting.

<p>Twelve fragmental genome sequences (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077912#pone-0077912-t001" target="_blank">Table 1</a>) are shown as one UGFM vision. Each individual primary genome fingerprint map (P-GFM) is classified into a discrete group solely based on its location: Group (A) (91.1.61, 913.1.77 and 10473.1.74), Group (B) (91.6.59, 913.5.57 and 13941.2.60), Group (C) (7946.4.7 and 12947.1.50), Group (D) (10498.4.86), Group (E) (91.1.1), and Group (F) (4431.1.70).</p

The quantitative analysis of representative taxa used in this study.

a<p>The taxa with GenBank_ID are cross-listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077912#pone-0077912-t001" target="_blank">Table 1</a>.</p>b<p>The Euclidean distance (),differentiate rate (), and weighted differentiate rate () are calculated according to the formula (<b>7</b>) by using two adjacent sequences in pairs; and the resultant is listed at the same upper row as the first sequence of the pairs, as shown by the last two rows.</p

The landscape of the UGFM-TGCC-SCG visions at large scale.

<p>(A). The twelve bacterial fragmental chromosomes of <i>E.coli</i> (II) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077912#pone-0077912-t001" target="_blank">Table 1</a>), twenty four virus genomes (I) and forty seven phage genomes (III) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077912#pone-0077912-t002" target="_blank">Table 2</a>) are shown as three distinct groups, resulting in fewer maps because the genomes are very close relatives and accordingly almost repeat themselves; (B). The representatives selected from (A) are shown as three distinct groups: two archaeal bacterial chromosomes (I); two bacterial fragmental chromosomes of <i>E.coli</i>, two viruses, and two phages (II); three plasmids (III). The strong effects of scale-down and view-angle rotation at large scale are demonstrated.</p