Model-based identification of conditionally-essential genes from transposon-insertion sequencing data.

The understanding of bacterial gene function has been greatly enhanced by recent advancements in the deep sequencing of microbial genomes. Transposon insertion sequencing methods combines next-generation sequencing techniques with transposon mutagenesis for the exploration of the essentiality of gen...

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Main Authors: Vishal Sarsani, Berent Aldikacti, Shai He, Rilee Zeinert, Peter Chien, Patrick Flaherty
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-03-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1009273
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author Vishal Sarsani
Berent Aldikacti
Shai He
Rilee Zeinert
Peter Chien
Patrick Flaherty
author_facet Vishal Sarsani
Berent Aldikacti
Shai He
Rilee Zeinert
Peter Chien
Patrick Flaherty
author_sort Vishal Sarsani
collection DOAJ
description The understanding of bacterial gene function has been greatly enhanced by recent advancements in the deep sequencing of microbial genomes. Transposon insertion sequencing methods combines next-generation sequencing techniques with transposon mutagenesis for the exploration of the essentiality of genes under different environmental conditions. We propose a model-based method that uses regularized negative binomial regression to estimate the change in transposon insertions attributable to gene-environment changes in this genetic interaction study without transformations or uniform normalization. An empirical Bayes model for estimating the local false discovery rate combines unique and total count information to test for genes that show a statistically significant change in transposon counts. When applied to RB-TnSeq (randomized barcode transposon sequencing) and Tn-seq (transposon sequencing) libraries made in strains of Caulobacter crescentus using both total and unique count data the model was able to identify a set of conditionally beneficial or conditionally detrimental genes for each target condition that shed light on their functions and roles during various stress conditions.
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spelling doaj.art-62eb5e3090604adcb422522af5ac6b6e2022-12-22T03:57:55ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582022-03-01183e100927310.1371/journal.pcbi.1009273Model-based identification of conditionally-essential genes from transposon-insertion sequencing data.Vishal SarsaniBerent AldikactiShai HeRilee ZeinertPeter ChienPatrick FlahertyThe understanding of bacterial gene function has been greatly enhanced by recent advancements in the deep sequencing of microbial genomes. Transposon insertion sequencing methods combines next-generation sequencing techniques with transposon mutagenesis for the exploration of the essentiality of genes under different environmental conditions. We propose a model-based method that uses regularized negative binomial regression to estimate the change in transposon insertions attributable to gene-environment changes in this genetic interaction study without transformations or uniform normalization. An empirical Bayes model for estimating the local false discovery rate combines unique and total count information to test for genes that show a statistically significant change in transposon counts. When applied to RB-TnSeq (randomized barcode transposon sequencing) and Tn-seq (transposon sequencing) libraries made in strains of Caulobacter crescentus using both total and unique count data the model was able to identify a set of conditionally beneficial or conditionally detrimental genes for each target condition that shed light on their functions and roles during various stress conditions.https://doi.org/10.1371/journal.pcbi.1009273
spellingShingle Vishal Sarsani
Berent Aldikacti
Shai He
Rilee Zeinert
Peter Chien
Patrick Flaherty
Model-based identification of conditionally-essential genes from transposon-insertion sequencing data.
PLoS Computational Biology
title Model-based identification of conditionally-essential genes from transposon-insertion sequencing data.
title_full Model-based identification of conditionally-essential genes from transposon-insertion sequencing data.
title_fullStr Model-based identification of conditionally-essential genes from transposon-insertion sequencing data.
title_full_unstemmed Model-based identification of conditionally-essential genes from transposon-insertion sequencing data.
title_short Model-based identification of conditionally-essential genes from transposon-insertion sequencing data.
title_sort model based identification of conditionally essential genes from transposon insertion sequencing data
url https://doi.org/10.1371/journal.pcbi.1009273
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