DOI: 10.1101/463901Nov 7, 2018Paper

Integrating Culture-based Antibiotic Resistance Profiles with Whole-genome Sequencing Data for 11,087 Clinical Isolates

BioRxiv : the Preprint Server for Biology
V. GalataAndreas Keller

Abstract

Emerging antibiotic resistance is a major global health threat. The analysis of nucleic acid sequences linked to susceptibility phenotypes facilitates the study of genetic antibiotic resistance determinants to inform molecular diagnostics and drug development. We collected genetic data (11,087 newly sequenced whole genomes) and culture-based resistance profiles (10,991 of 11,087 isolates were comprehensively tested against 22 antibiotics in total) of clinical isolates including 18 main species spanning a time period of 30 years. Species and drug specific resistance patterns could be observed including increasing resistance rates for Acinetobacter baumannii to carbapenems and for Escherichia coli to fluoroquinolones. Species-level pan-genomes were constructed to reflect the genetic repertoire of the respective species such as conserved essential genes and known resistance factors. Integrating phenotypes and genotypes through species-level pan-genomes allowed to infer gene-drug resistance associations using statistical testing. The isolate collection and the analysis results have been integrated into a resource, GEAR-base, available for academic research use free of charge at https://gear-base.com.

Methods Mentioned

BETA
PCA

Software Mentioned

PubMLST
EDGAR
BWA
hmmsearch
PCA
kraken
BusyBee Web
MYSTIC
fastCor
PTHREADS

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