Evidence map›Paper›PMID 28974199›Full record

ArticleBMC bioinformatics2017

Tissue-aware RNA-Seq processing and normalization for heterogeneous and sparse data.

Joseph N Paulson, Cho-Yi Chen, Camila M Lopes-Ramos, Marieke L Kuijjer, John Platig, Abhijeet R Sonawane, Maud Fagny, Kimberly Glass, John Quackenbush

Abstract read
In one paragraph

Article in BMC bioinformatics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
–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

31 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Challenges and Opportunities in Single-Sample Network Modeling.bioRxiv : the preprint server for biology · 2026
    Article
  3. Review
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  14. Immune activation duringiScience · 2021
    Article
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  16. Article
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  18. PUMA: PANDA Using MicroRNA Associations.Bioinformatics (Oxford, England) · 2020
    Article
  19. Article
  20. 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.

Joseph N PaulsonDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Cho-Yi ChenDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Camila M Lopes-RamosDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Marieke L KuijjerDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
John PlatigDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Abhijeet R SonawaneChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02215, USA.
Maud FagnyDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Kimberly GlassDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
John QuackenbushDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. johnq@jimmy.harvard.edu.

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI A. Heather Eliassen · 1985 to 2026
$330.6M
Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Benjamin Harris Kann · 2013 to 2026
$33.5M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2M
Respiratory Computational Discovery CoreP01HL114501 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHOI, MARY E · 2013 to 2025
$24.9M
SYSTEMS APPROACHES TO THE EPIDEMIOLOGY, GENETICS AND GENOMICS OF LUNG DISEASEST32HL007427 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI DAWN L DEMEO, Edwin K Silverman · 1985 to 2026
$13.6M
Systems Biology, Bioinformatics, and BiostatisticsP01HL105339 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2011 to 2015
$12.2M
Statistical Methods for Analysis of Massive Genetic and Genomic Data in Cancer ResearchR35CA197449 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI XIHONG LIN · 2015 to 2026
$10.9M
Chemical Inhibitors to Define an Essential M. Tuberculosis Signaling NetworkR01AI099204 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI HUSSON, ROBERT N · 2012 to 2016
$6.1M
Using Networks to Assign Gene Function in Lung DiseaseR01HL111759 · NHLBI · DANA-FARBER CANCER INST · PI QUACKENBUSH, JOHN, SILVERMAN, EDWIN K · 2012 to 2015
$3.4M
Genotype and Imaging Phenotype Biomarkers in Lung CancerU01CA190234 · NCI · DANA-FARBER CANCER INST · PI AERTS, HUGO, QUACKENBUSH, JOHN · 2015 to 2019
$3.3M
Using Integrative Networks to Explore Heterogeneous Phenotypes in COPDK25HL133599 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GLASS, KIMBERLY RENEE · 2016 to 2020
$945k
NCI NIH HHS P30 CA006516NCI NIH HHS P50 CA127003NCI NIH HHS P50 CA165962NCI NIH HHS R35 CA197449NCI NIH HHS U01 CA190234NHLBI NIH HHS K25 HL133599NHLBI NIH HHS P01 HL105339NHLBI NIH HHS P01 HL114501NHLBI NIH HHS R01 HL111759NIAID NIH HHS R01 AI099204
6 · The paper itself

Abstract

backgroundAlthough ultrahigh-throughput RNA-Sequencing has become the dominant technology for genome-wide transcriptional profiling, the vast majority of RNA-Seq studies typically profile only tens of samples, and most analytical pipelines are optimized for these smaller studies. However, projects are generating ever-larger data sets comprising RNA-Seq data from hundreds or thousands of samples, often collected at multiple centers and from diverse tissues. These complex data sets present significant analytical challenges due to batch and tissue effects, but provide the opportunity to revisit the assumptions and methods that we use to preprocess, normalize, and filter RNA-Seq data - critical first steps for any subsequent analysis.

resultsWe find that analysis of large RNA-Seq data sets requires both careful quality control and the need to account for sparsity due to the heterogeneity intrinsic in multi-group studies. We developed Yet Another RNA Normalization software pipeline (YARN), that includes quality control and preprocessing, gene filtering, and normalization steps designed to facilitate downstream analysis of large, heterogeneous RNA-Seq data sets and we demonstrate its use with data from the Genotype-Tissue Expression (GTEx) project.

conclusionsAn R package instantiating YARN is available at http://bioconductor.org/packages/yarn .

Indexed as

Databases, GeneticGene Expression ProfilingGene Expression RegulationHumansMolecular Sequence AnnotationOrgan SpecificityPrincipal Component AnalysisQuality ControlReference StandardsSample SizeSequence Analysis, RNASoftwareFilteringGTExNormalizationPreprocessingQuality controlRNA-Seq

Identifiers

PMID28974199
PMCPMC5627434

What OpenQuestion holds

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LicenceCC BY
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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.