Computational pan-genome mapping and pairwise SNP-distance improve detection of Mycobacterium tuberculosis transmission clusters.

Christine Jandrasits,Walter Haas,Bernhard Y Renard,Stefan Kröger,Sergei L Kosakovsky Pond

doi:10.1371/journal.pcbi.1007527

Christine Jandrasits, Walter Haas + Show 3 more

Open Access

https://doi.org/10.1371/journal.pcbi.1007527

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Journal: PLoS computational biology	Publication Date: Dec 9, 2019
Citations: 14	License type: CC BY 4.0

Affiliation: Robert Koch Institute

Abstract

Next-generation sequencing based base-by-base distance measures have become an integral complement to epidemiological investigation of infectious disease outbreaks. This study introduces PANPASCO, a computational pan-genome mapping based, pairwise distance method that is highly sensitive to differences between cases, even when located in regions of lineage specific reference genomes. We show that our approach is superior to previously published methods in several datasets and across different Mycobacterium tuberculosis lineages, as its characteristics allow the comparison of a high number of diverse samples in one analysis—a scenario that becomes more and more likely with the increased usage of whole-genome sequencing in transmission surveillance.

Highlights

Genotyping and sequencing methods have revolutionized infectious disease surveillance
We show that our approach is superior to previously published methods in several datasets and across different Mycobacterium tuberculosis lineages, as its characteristics allow the comparison of a high number of diverse samples in one analysis—a scenario that becomes more and more likely with the increased usage of whole-genome sequencing in transmission surveillance
We developed PANPASCO, a novel method to determine the distance between samples based on single nucleotide polymorphisms (SNP) differences

Summary

Introduction

Genotyping and sequencing methods have revolutionized infectious disease surveillance. The employed methods shifted from fingerprinting, e.g. variable number tandem repeat (VNTR) methods, and sequence-based genotyping assays, such as bacterial multilocus sequence typing (MLST) to next-generation sequencing (NGS) based whole genome sequencing (WGS) in recent years [1]. WGS allows for the comparison of pathogens on the level of single nucleotide polymorphisms (SNP) and is useful for the transmission analysis of stable genomes with low mutation rates such as Mycobacterium tuberculosis. Between 2000 and 2016 TB caused 53 million deaths. The WHO estimates more than 1.7 million deaths (including HIV coinfection) and 10.4 million new TB infections in 2016 only [5]

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