Evidence map›Paper›PMID 30400812›Full record

ArticleBMC genomics2018

Analysis and correction of compositional bias in sparse sequencing count data.

M Senthil Kumar, Eric V Slud, Kwame Okrah, Stephanie C Hicks, Sridhar Hannenhalli, Héctor Corrada Bravo

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

64 citing papers in PubMed, 136 citations in OpenAlex.

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  7. Design, processing, and modeling for longitudinal multiomics microbiome data.Frontiers in cellular and infection microbiology · 2026
    Review
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4 more citing papers are in PubMed but not listed here.

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

6 authors at 3 institutions in 1 country.

M Senthil KumarGraduate Program in Bioinformatics, University of Maryland, College Park, MD, USA. smuthiah@umiacs.umd.edu.
Eric V SludDepartment of Mathematics, University of Maryland, College Park, MD, USA.
Kwame OkrahGRED Oncology Biostatistics, Genentech, San Francisco, CA, USA.
Stephanie C HicksBiostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard University, Boston, MA, USA.
Sridhar HannenhalliCenter for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.
Héctor Corrada BravoCenter for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.
University of Maryland, College Park · USCancer Research And Biostatistics · USUnited States Census Bureau · US

Funding

Preprocessing and Analysis Tools for High-Throughput TechnologiesR01GM083084 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2007 to 2018
$4.4M
Overcoming bias and unwanted variability in next generation sequencingR01HG005220 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2010 to 2018
$3.6M
Integrative Visual and Computational Exploratory Analysis of Genomics DataR01GM114267 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI CORRADA BRAVO, HECTOR · 2015 to 2018
$1.8M
Software for the Statistical Analysis of Microarray Probe Level DataR01RR021967 · NCRR · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2007 to 2011
$1.2M
Software for the statistical analysis of microarray probe level dataR01GM103552 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2012 to 2013
$735k
Statistical Methods for the Normalization and Quantification of Single-Cell RNA-Sequencing DataR00HG009007 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI HICKS, STEPHANIE CARINNE · 2018 to 2020
$725k
Identifying the dynamics of small and large microbial communitiesR21GM107683 · NIGMS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI CHUNG, MATTHIAS · 2013 to 2014
$313k
Statistical Methods for the Normalization and Quantification of Single-Cell RNA-Sequencing DataK99HG009007 · NHGRI · DANA-FARBER CANCER INST · PI HICKS, STEPHANIE CARINNE · 2017 to 2018
$124k
National Science Foundation (US) 1564785NCRR NIH HHS R01 RR021967NHGRI NIH HHS K99 HG009007NHGRI NIH HHS R00 HG009007NHGRI NIH HHS R01 HG005220NIGMS NIH HHS R01 GM083084NIGMS NIH HHS R01 GM103552NIGMS NIH HHS R01 GM114267NIGMS NIH HHS R21 GM107683NIH HHS GM083084NIH HHS GM114267NIH HHS HG005220
6 · The paper itself

Abstract

backgroundCount data derived from high-throughput deoxy-ribonucliec acid (DNA) sequencing is frequently used in quantitative molecular assays. Due to properties inherent to the sequencing process, unnormalized count data is compositional, measuring relative and not absolute abundances of the assayed features. This compositional bias confounds inference of absolute abundances. Commonly used count data normalization approaches like library size scaling/rarefaction/subsampling cannot correct for compositional or any other relevant technical bias that is uncorrelated with library size.

resultsWe demonstrate that existing techniques for estimating compositional bias fail with sparse metagenomic 16S count data and propose an empirical Bayes normalization approach to overcome this problem. In addition, we clarify the assumptions underlying frequently used scaling normalization methods in light of compositional bias, including scaling methods that were not designed directly to address it.

conclusionsCompositional bias, induced by the sequencing machine, confounds inferences of absolute abundances. We present a normalization technique for compositional bias correction in sparse sequencing count data, and demonstrate its improved performance in metagenomic 16s survey data. Based on the distribution of technical bias estimates arising from several publicly available large scale 16s count datasets, we argue that detailed experiments specifically addressing the influence of compositional bias in metagenomics are needed.

Indexed as

AlgorithmsMicrobiotaBayes TheoremComputational BiologyHigh-Throughput Nucleotide SequencingMetagenomicsRNA, Ribosomal, 16SRNA, Ribosomal, 16SAbsolute abundanceCompositional biasCount dataData integrationEmpirical BayesMetagenomicsNormalizationscRNAseqSpike-in

Identifiers

PMID30400812
PMCPMC6219007
OpenAlexW2950612336

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.