Evidence map›Paper›PMID 22769017›Full record

ArticleBMC genomics2012

Technical and biological variance structure in mRNA-Seq data: life in the real world.

Ann L Oberg, Brian M Bot, Diane E Grill, Gregory A Poland, Terry M Therneau

Abstract read
In one paragraph

Article in BMC genomics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

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  16. Calculating sample size estimates for RNA sequencing data.Journal of computational biology : a journal of computational molecular cell biology · 2013
    Article
  17. Impact of bioinformatic procedures in the development and translation of high-throughput molecular classifiers in oncology.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013
    Review
  18. Article
  19. Article
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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

5 authors.

Ann L ObergDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA. oberg.ann@mayo.edu
Brian M Bot
Diane E Grill
Gregory A Poland
Terry M Therneau

Funding

MAYO CLINIC CENTER FOR TRANSLATIONAL SCIENCE ACTIVITIESUL1RR024150 · NCRR · MAYO CLINIC ROCHESTER · PI RIZZA, ROBERT A. · 2006 to 2011
$66.4M
Bioinformatics Approach to Influenza A/H1N1 Vaccine Immune ProfilingU01AI089859 · NIAID · MAYO CLINIC ROCHESTER · PI POLAND, GREGORY A. · 2010 to 2015
$33.8M
Immunogenetic Mechanisms of Vaccine ResponseR37AI048793 · NIAID · MAYO CLINIC ROCHESTER · PI POLAND, GREGORY A. · 2011 to 2020
$5.4M
IMMUNOGENETIC MECHANISMS OF VACCINE RESPONSER01AI048793 · NIAID · MAYO CLINIC ROCHESTER · PI POLAND, GREGORY A. · 2001 to 2010
$4.3M
NCRR NIH HHS 1 UL1 RR024150NIAID NIH HHS AI48793NIAID NIH HHS AI-89859NIAID NIH HHS N01-AI40065NIAID NIH HHS U01 AI089859
6 · The paper itself

Abstract

backgroundmRNA expression data from next generation sequencing platforms is obtained in the form of counts per gene or exon. Counts have classically been assumed to follow a Poisson distribution in which the variance is equal to the mean. The Negative Binomial distribution which allows for over-dispersion, i.e., for the variance to be greater than the mean, is commonly used to model count data as well.

resultsIn mRNA-Seq data from 25 subjects, we found technical variation to generally follow a Poisson distribution as has been reported previously and biological variability was over-dispersed relative to the Poisson model. The mean-variance relationship across all genes was quadratic, in keeping with a Negative Binomial (NB) distribution. Over-dispersed Poisson and NB distributional assumptions demonstrated marked improvements in goodness-of-fit (GOF) over the standard Poisson model assumptions, but with evidence of over-fitting in some genes. Modeling of experimental effects improved GOF for high variance genes but increased the over-fitting problem.

conclusionsThese conclusions will guide development of analytical strategies for accurate modeling of variance structure in these data and sample size determination which in turn will aid in the identification of true biological signals that inform our understanding of biological systems.

Indexed as

Models, StatisticalAdolescentAntibodiesBinomial DistributionChildFemaleHumansImmunity, HumoralPoisson DistributionRNA, MessengerRubellaRubella VaccineYoung AdultAntibodiesRNA, MessengerRubella Vaccine

Identifiers

PMID22769017
PMCPMC3505161

What OpenQuestion holds

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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.