Evidence map›Paper›PMID 32066774›Full record

ArticleScientific reports2020

Variability in estimated gene expression among commonly used RNA-seq pipelines.

Sonali Arora, Siobhan S Pattwell, Eric C Holland, Hamid Bolouri

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 2 pooled it
3.8field-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

39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.

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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

4 authors at 2 institutions in 2 countries.

Sonali AroraDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Siobhan S PattwellDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Eric C HollandDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. eholland@fredhutch.org.ORCID http://orcid.org/0000-0002-3792-7120
Hamid BolouriDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. hbolouri@fredhutch.org.ORCID https://orcid.org/0000-0001-8068-426X
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAFred Hutch Cancer Center · US

Funding

Project 3: Single Cell Measures of Intratumor Diversity for Optimal Breast Cancer TherapyU54CA193461 · NCI · DANA-FARBER CANCER INST · PI POLYAK, KORNELIA · 2015 to 2020
$11.2M
Stem Cell and Transplantation BiologyU54DK106829 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DEREK L STIREWALT · 2015 to 2026
$9.1M
Chromosome Metabolism and Cancer Training GrantT32CA009657 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI EISENMAN, ROBERT NEIL · 1991 to 2020
$7.6M
Critical role for a TrkB splice variant in oncogenic signalingR21CA223531 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HOLLAND, ERIC C. · 2018 to 2019
$415k
NCI NIH HHS R21 CA223531NCI NIH HHS T32 CA009657NCI NIH HHS U54 CA193461NIDDK NIH HHS U54 DK106829
6 · The paper itself

Abstract

RNA-sequencing data is widely used to identify disease biomarkers and therapeutic targets using numerical methods such as clustering, classification, regression, and differential expression analysis. Such approaches rely on the assumption that mRNA abundance estimates from RNA-seq are reliable estimates of true expression levels. Here, using data from five RNA-seq processing pipelines applied to 6,690 human tumor and normal tissues, we show that nearly 88% of protein-coding genes have similar gene expression profiles across all pipelines. However, for >12% of protein-coding genes, current best-in-class RNA-seq processing pipelines differ in their abundance estimates by more than four-fold when applied to exactly the same samples and the same set of RNA-seq reads. Expression fold changes are similarly affected. Many of the impacted genes are widely studied disease-associated genes. We show that impacted genes exhibit diverse patterns of discordance among pipelines, suggesting that many inter-pipeline differences contribute to overall uncertainty in mRNA abundance estimates. A concerted, community-wide effort will be needed to develop gold-standards for estimating the mRNA abundance of the discordant genes reported here. In the meantime, our list of discordantly evaluated genes provides an important resource for robust marker discovery and target selection.

Indexed as

Gene Expression Regulation, NeoplasticCCAAT-Enhancer-Binding ProteinsErb-b2 Receptor Tyrosine KinasesExome SequencingGene Expression ProfilingGenetic VariationHigh-Throughput Nucleotide SequencingHumansNeoplasm ProteinsNeoplasmsNuclear ProteinsNucleophosminPlatelet-Derived Growth FactorPrincipal Component AnalysisSequence Analysis, RNASplicing Factor U2AFCCAAT-Enhancer-Binding ProteinsCEBPA protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesNeoplasm ProteinsNuclear ProteinsNucleophosminPlatelet-Derived Growth Factorplatelet-derived growth factor ASplicing Factor U2AFU2AF1 protein, human

Identifiers

PMID32066774
PMCPMC7026138
OpenAlexW3006025691

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.