Whole-Genome-Based Helicobacter pylori Geographic Surveillance: A Visualized and Expandable Webtool

Abstract

Helicobacter pylori exhibit specific geographic distributions that are related to clinical outcomes. Despite the high infection rate of H. pylori throughout the world, the genetic epidemiology surveillance of H. pylori still needs to be improved. This study used the single nucleotide polymorphisms (SNPs) profiling approach based on whole genome sequencing (WGS) to facilitate genomic population analyses of H. pylori and encourage the dissemination of microbial genotyping strategies worldwide. A total number of 1,211 public H. pylori genomes were downloaded and used to construct the typing tool, named HpTT (H. pylori Typing Tool). Combined with the metadata, we developed two levels of genomic typing, including a continent-scale and a country scale that nested in the continent scale. Results showed that Asia was the largest isolate source in our dataset, while isolates from Europe and Oceania were comparatively more widespread. More specifically, Switzerland and Australia are the main sources of widespread isolates in their corresponding continents. To integrate all the typing information and enable researchers to compare their dataset against the existing global database easily and rapidly, a user-friendly website (https://db.cngb.org/HPTT/) was developed with both genomic typing tools and visualization tools. To further confirm the validity of the website, ten newly assembled genomes were downloaded and tested precisely located on the branch as we expected. In summary, the H. pylori typing tool (HpTT) is a novel genomic epidemiological tool that can achieve high-resolution analysis of genomic typing and visualizing simultaneously, providing insights into the genetic population structure, evolution analysis, and epidemiological surveillance of H. pylori.

Keywords: Helicobacter pylori; antibiotic-resistant; genomic; genotyping; phylogenetic; webtool; whole-genome sequencing.

FIGURE 1

Two clades of geographic typing based on the WGS. The HpTT enrolled 1,211 H. pylori genomes downloaded from NCBI. The clade nodes in each figure correspond to (A) G groups for continent level of typing, (B) the continent that isolates collected from, (C) C groups for country-level typing, (D) the country that isolates were collected from. (E) the hp Class and hsp Class, (F) G groups for continent level of typing with group names. Numbers in parenthesis refer to the number of isolates in each genogroup.

FIGURE 2

Geographical clustering of H. pylori continent clades. The number in each cube represents the percentage of unique isolates sourced from each of the continents. A total number of 37 continent-level groups were defined. The deeper the color, the higher the percentage of the isolates in that continent level of clade groups. A phylogenetic tree is also shown on the left side of the table. Background information on the isolates is provided in Supplementary Table 1.

FIGURE 3

Geographical clustering of H. pylori country subclades. The number in each cube represents the percentage of unique isolates sourced from each of the countries in that continent group. A total number of 216 country-level groups were defined. The deeper the color, the higher the percentage of the isolates sourced from that country in continent-level groups. Background information on isolates is provided in Supplementary Table 1.

FIGURE 4

The HpTT workflow. The SNP-based genotyping approach can be used with the Whole Genome Sequencing (WGS) data, which can be acquired in the following ways: DNA can be extracted from a pure cultured bacterial cell with WGS data or a community sample with metagenomic sequencing data. After being sequenced by an appropriate platform, the assembled genomes can be directly submitted to our database. In addition, the public assembled data can also be directly submitted to our database. The downstream analyses of the aligned sequence data can be linked to the phylogenetic and geographic page.