Brief Article
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World J Gastroenterol. Aug 14, 2013; 19(30): 5006-5010
Published online Aug 14, 2013. doi: 10.3748/wjg.v19.i30.5006
Predicting a novel pathogenicity island in Helicobacter pylori by genomic barcoding
Guo-Qing Wang, Jian-Ting Xu, Guang-Yu Xu, Yang Zhang, Fan Li, Jian Suo
Guo-Qing Wang, Yang Zhang, Jian Suo, Gastrointestinal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Guo-Qing Wang, Guang-Yu Xu, Fan Li, Department of Pathogenobiology, Norman Bethune Medical College of Jilin University, Changchun 130021, Jilin Province, China
Jian-Ting Xu, Cancer Centre, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Wang GQ performed the research; Xu JT and Xu GY collected the data; Zhang Y analyzed the data; Li F and Suo J conceived and designed the study; Wang GQ wrote the manuscript.
Supported by Grants from the National Natural Science Foundation of China, No. 81271897 and 81071424; the National Basic Research Program of China 973 Program, No. 2011CB512003; the Specialized Research Fund for the Doctoral Program of Higher Education of China, No. 20110061120093; the China Postdoctoral Science Foundation, No. 20110491311 and 2012T50285; the Foundation of Xinjiang Provincial Science and Technology Department, No. 201091148; the Foundation of Jilin Provincial Health Department, No. 2011Z049; and the Norman Bethune Program of Jilin University, No. 2012219
Correspondence to: Jian Suo, PhD, Gastrointestinal Surgery, First Hospital of Jilin University, Jiefang Road 3808, Changchun 130021, Jilin Province, China.
Telephone: +86-431-85619574 Fax: +86-431-85619107
Received: April 15, 2013
Revised: June 4, 2013
Accepted: June 8, 2013
Published online: August 14, 2013

AIM: To apply a new, integrated technique for visualizing bacterial genomes to identify novel pathogenicity islands in Helicobacter pylori (H. pylori).

METHODS: A genomic barcode imaging method (converting frequency matrices to grey-scale levels) was designed to visually distinguish origin-specific genomic regions in H. pylori. The complete genome sequences of the six H. pylori strains published in the National Center for Biotechnological Information prokaryotic genome database were scanned, and compared to the genome barcodes of Escherichia coli (E. coli) O157:H7 strain EDL933 and a random nucleotide sequence. The following criteria were applied to identify potential pathogenicity islands (PAIs): (1) barcode distance distinct from that of the general background; (2) length greater than 10000 continuous base pairs; and (3) containing genes with known virulence-related functions (as determined by PfamScan and Blast2GO).

RESULTS: Comparison of the barcode images generated for the 26695, HPAG1, J99, Shi470, G27 and P12 H. pylori genomes with those for the E. coli and random sequence controls revealed that H. pylori genomes contained fewer anomalous regions. Among the H. pylori-specific continuous anomalous regions (longer than 20 kbp in each strain’s genome), two fit the criteria for identifying candidate PAIs. The bioinformatic-based functional analyses revealed that one of the two anomalous regions was the known pathogenicity island cag-PAI, this finding also served as proof-of-principle for the utility of the genomic barcoding approach for identifying PAIs, and characterized the other as a novel PAI, which was designated as tfs3-PAI. Furthermore, the cag-PAI and tfs3-PAI harbored genes encoding type IV secretion system proteins and were predicted to have potential for functional synergy.

CONCLUSION: Genomic barcode imaging represents an effective bioinformatic-based approach for scanning bacterial genomes, such as H. pylori, to identify candidate PAIs.

Keywords: Helicobacter pylori, Genome analysis, Pathogenicity islands, Genomic bar coding

Core tip: The genomic barcoding technology was recently developed to increase the accuracy of genome analysis, and has facilitated the identification of origin-specific genomic regions of both eukaryotic and prokaryotic lifeforms. In this study, we applied the genomic barcode imaging approach to screen for pathogenicity islands (PAIs) in Helicobacter pylori using the six strains for which the complete genome sequences have been published and performing comparison to a common Enterobacter species. Bioinformatic-based functional analysis not only provided proof-of-principle (identifying the known cag-PAI) but also identified a novel PAI (designated as tsf3-PAI).