Evidence map›Paper›PMID 31752678›Full record

ArticleBMC bioinformatics2019

Statistical analysis of variability in TnSeq data across conditions using zero-inflated negative binomial regression.

Siddharth Subramaniyam, Michael A DeJesus, Anisha Zaveri, Clare M Smith, Richard E Baker, Sabine Ehrt, Dirk Schnappinger, Christopher M Sassetti, Thomas R Ioerger

Open access · goldAbstract read
In one paragraph

Article in BMC bioinformatics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
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  6. Article
  7. Analysis of Gene Essentiality from TnSeq Data Using Transit.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  8. Article
  9. Oxidative damage and delayed replication allow viableScience translational medicine · 2021
    Article
  10. Article
  11. Article
  12. Review
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  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Siddharth SubramaniyamDepartment of Computer Science & Engineering, Texas A&M Univeristy, College Station, TX, USA.
Michael A DeJesusRockefeller University, New York, NY, USA.
Anisha ZaveriDepartment of Microbiology & Immunology, Weill Cornell Medical College, New York, NY, USA.
Clare M SmithDepartment of Microbiology & Physiological Systems, University of Massachusetts Medical School, Worchester, MA, USA.
Richard E BakerDepartment of Microbiology & Physiological Systems, University of Massachusetts Medical School, Worchester, MA, USA.
Sabine EhrtDepartment of Microbiology & Immunology, Weill Cornell Medical College, New York, NY, USA.
Dirk SchnappingerDepartment of Microbiology & Immunology, Weill Cornell Medical College, New York, NY, USA.
Christopher M SassettiDepartment of Microbiology & Physiological Systems, University of Massachusetts Medical School, Worchester, MA, USA.
Thomas R IoergerDepartment of Computer Science & Engineering, Texas A&M Univeristy, College Station, TX, USA. ioerger@cs.tamu.edu.ORCID http://orcid.org/0000-0001-8702-9102
Cornell University · USUniversity of Massachusetts Chan Medical School · USTexas A&M University · USRockefeller University · US

Funding

The roles of genes critical for growth under defined conditions in vitro or duriU19AI107774 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI CARR, STEVEN A, FORTUNE, SARAH · 2013 to 2017
$13.2M
Systems Genetics of TuberculosisP01AI132130 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BEHAR, SAMUEL M · 2017 to 2021
$11.2M
National Institute of Allergy and Infectious Diseases AI107774NIAID NIH HHS P01 AI132130NIAID NIH HHS U19 AI107774
6 · The paper itself

Abstract

backgroundDeep sequencing of transposon mutant libraries (or TnSeq) is a powerful method for probing essentiality of genomic loci under different environmental conditions. Various analytical methods have been described for identifying conditionally essential genes whose tolerance for insertions varies between two conditions. However, for large-scale experiments involving many conditions, a method is needed for identifying genes that exhibit significant variability in insertions across multiple conditions.

resultsIn this paper, we introduce a novel statistical method for identifying genes with significant variability of insertion counts across multiple conditions based on Zero-Inflated Negative Binomial (ZINB) regression. Using likelihood ratio tests, we show that the ZINB distribution fits TnSeq data better than either ANOVA or a Negative Binomial (in a generalized linear model). We use ZINB regression to identify genes required for infection of M. tuberculosis H37Rv in C57BL/6 mice. We also use ZINB to perform a analysis of genes conditionally essential in H37Rv cultures exposed to multiple antibiotics.

conclusionsOur results show that, not only does ZINB generally identify most of the genes found by pairwise resampling (and vastly out-performs ANOVA), but it also identifies additional genes where variability is detectable only when the magnitudes of insertion counts are treated separately from local differences in saturation, as in the ZINB model.

Indexed as

Databases, GeneticHigh-Throughput Nucleotide SequencingModels, StatisticalAnimalsAnti-Bacterial AgentsBinomial DistributionDNA Transposable ElementsGenes, EssentialLikelihood FunctionsLinear ModelsMice, Inbred C57BLMycobacterium tuberculosisAnti-Bacterial AgentsDNA Transposable ElementsEssentialityMycobacterium tuberculosisTnSeqTransposon insertion libraryZero-inflated negative binomial distribution

Identifiers

PMID31752678
PMCPMC6873424
OpenAlexW2991307198

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.