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Predicting bacterial resistance from whole-genome sequences using k-mers and stability selection

Identifieur interne : 000853 ( Main/Exploration ); précédent : 000852; suivant : 000854

Predicting bacterial resistance from whole-genome sequences using k-mers and stability selection

Auteurs : Pierre Mahé ; Maud Tournoud

Source :

RBID : PMC:6192184

Descripteurs français

English descriptors

Abstract

Background

Several studies demonstrated the feasibility of predicting bacterial antibiotic resistance phenotypes from whole-genome sequences, the prediction process usually amounting to detecting the presence of genes involved in antibiotic resistance mechanisms, or of specific mutations, previously identified from a training panel of strains, within these genes. We address the problem from the supervised statistical learning perspective, not relying on prior information about such resistance factors. We rely on a k-mer based genotyping scheme and a logistic regression model, thereby combining several k-mers into a probabilistic model. To identify a small yet predictive set of k-mers, we rely on the stability selection approach (Meinshausen et al., J R Stat Soc Ser B 72:417–73, 2010), that consists in penalizing logistic regression models with a Lasso penalty, coupled with extensive resampling procedures.

Results

Using public datasets, we applied the resulting classifiers to two bacterial species and achieved predictive performance equivalent to state of the art. The models are extremely sparse, involving 1 to 8 k-mers per antibiotic, hence are remarkably easy and fast to evaluate on new genomes (from raw reads to assemblies).

Conclusion

Our proof of concept therefore demonstrates that stability selection is a powerful approach to investigate bacterial genotype-phenotype relationships.

Electronic supplementary material

The online version of this article (10.1186/s12859-018-2403-z) contains supplementary material, which is available to authorized users.


Url:
DOI: 10.1186/s12859-018-2403-z
PubMed: 30332990
PubMed Central: 6192184


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<term>Drug Resistance, Bacterial (drug effects)</term>
<term>Drug Resistance, Bacterial (genetics)</term>
<term>Genome, Bacterial</term>
<term>Logistic Models</term>
<term>Models, Genetic</term>
<term>Mycobacterium tuberculosis (drug effects)</term>
<term>Mycobacterium tuberculosis (genetics)</term>
<term>ROC Curve</term>
<term>Reproducibility of Results</term>
<term>Staphylococcus aureus (drug effects)</term>
<term>Staphylococcus aureus (genetics)</term>
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<term>Algorithmes</term>
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<term>Génome bactérien</term>
<term>Modèles génétiques</term>
<term>Modèles logistiques</term>
<term>Mycobacterium tuberculosis ()</term>
<term>Mycobacterium tuberculosis (génétique)</term>
<term>Reproductibilité des résultats</term>
<term>Résistance bactérienne aux médicaments ()</term>
<term>Résistance bactérienne aux médicaments (génétique)</term>
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<title>Background</title>
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<italic>k</italic>
-mer based genotyping scheme and a logistic regression model, thereby combining several
<italic>k</italic>
-mers into a probabilistic model. To identify a small yet predictive set of
<italic>k</italic>
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