ARTIST: High-Resolution Genome-Wide Assessment of Fitness Using Transposon-Insertion Sequencing

Justin R. Pritchard, Michael C. Chao, Sören Abel, Brigid M. Davis, Catherine Baranowski, Yanjia J. Zhang, Eric J. Rubin, Matthew K. Waldor

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Transposon-insertion sequencing (TIS) is a powerful approach for deciphering genetic requirements for bacterial growth in different conditions, as it enables simultaneous genome-wide analysis of the fitness of thousands of mutants. However, current methods for comparative analysis of TIS data do not adjust for stochastic experimental variation between datasets and are limited to interrogation of annotated genomic elements. Here, we present ARTIST, an accessible TIS analysis pipeline for identifying essential regions that are required for growth under optimal conditions as well as conditionally essential loci that participate in survival only under specific conditions. ARTIST uses simulation-based normalization to model and compensate for experimental noise, and thereby enhances the statistical power in conditional TIS analyses. ARTIST also employs a novel adaptation of the hidden Markov model to generate statistically robust, high-resolution, annotation-independent maps of fitness-linked loci across the entire genome. Using ARTIST, we sensitively and comprehensively define Mycobacterium tuberculosis and Vibrio cholerae loci required for host infection while limiting inclusion of false positive loci. ARTIST is applicable to a broad range of organisms and will facilitate TIS-based dissection of pathways required for microbial growth and survival under a multitude of conditions.

Original languageEnglish (US)
JournalPLoS genetics
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2014

Fingerprint

transposons
fitness
genome
Genome
Growth
loci
cholera
tuberculosis
Vibrio cholerae
dissection
microbial growth
Mycobacterium tuberculosis
Noise
Dissection
genomics
Theoretical Models
Infection
simulation
analysis
mutants

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Pritchard, Justin R. ; Chao, Michael C. ; Abel, Sören ; Davis, Brigid M. ; Baranowski, Catherine ; Zhang, Yanjia J. ; Rubin, Eric J. ; Waldor, Matthew K. / ARTIST : High-Resolution Genome-Wide Assessment of Fitness Using Transposon-Insertion Sequencing. In: PLoS genetics. 2014 ; Vol. 10, No. 11.
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Pritchard, JR, Chao, MC, Abel, S, Davis, BM, Baranowski, C, Zhang, YJ, Rubin, EJ & Waldor, MK 2014, 'ARTIST: High-Resolution Genome-Wide Assessment of Fitness Using Transposon-Insertion Sequencing', PLoS genetics, vol. 10, no. 11. https://doi.org/10.1371/journal.pgen.1004782

ARTIST : High-Resolution Genome-Wide Assessment of Fitness Using Transposon-Insertion Sequencing. / Pritchard, Justin R.; Chao, Michael C.; Abel, Sören; Davis, Brigid M.; Baranowski, Catherine; Zhang, Yanjia J.; Rubin, Eric J.; Waldor, Matthew K.

In: PLoS genetics, Vol. 10, No. 11, 01.11.2014.

Research output: Contribution to journalArticle

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