Evidence map›Paper›PMID 36936082›Full record

ArticleCell reports methods2023

Blood RNA alternative splicing events as diagnostic biomarkers for infectious disease.

Zijun Zhang, Natalie Sauerwald, Antonio Cappuccio, Irene Ramos, Venugopalan D Nair, German Nudelman, Elena Zaslavsky, Yongchao Ge, Angelo Gaitas, Hui Ren and 16 more

Abstract read
In one paragraph

Article in Cell reports methods, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. 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

26 authors.

Zijun ZhangCenter for Computational Biology, Flatiron Institute, New York, NY 10010, USA.
Natalie SauerwaldCenter for Computational Biology, Flatiron Institute, New York, NY 10010, USA.
Antonio CappuccioDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Irene RamosDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Venugopalan D NairDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
German NudelmanDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Elena ZaslavskyDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Yongchao GeDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Angelo GaitasDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Hui RenFluidigm Corporation, South San Francisco, CA 94080, USA.
Joel BrockmanFluidigm Corporation, South San Francisco, CA 94080, USA.
Jennifer GeisFluidigm Corporation, South San Francisco, CA 94080, USA.
Naveen RamalingamFluidigm Corporation, South San Francisco, CA 94080, USA.
David KingFluidigm Corporation, South San Francisco, CA 94080, USA.
Micah T McClainCenter for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Christopher W WoodsCenter for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Ricardo HenaoCenter for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Thomas W BurkeCenter for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Ephraim L TsalikCenter for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Carl W GoforthNaval Medical Research Center, Silver Spring, MD, USA.
Rhonda A LizewskiNaval Medical Research Unit SIX, Lima, Peru.
Stephen E LizewskiNaval Medical Research Unit SIX, Lima, Peru.
Dawn L WeirNaval Medical Research Center, Silver Spring, MD, USA.
Andrew G LetiziaNaval Medical Research Center, Silver Spring, MD, USA.
Stuart C SealfonDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Olga G TroyanskayaCenter for Computational Biology, Flatiron Institute, New York, NY 10010, USA.

Funding

lntegration and Visualization of Diverse Biological DataR01GM071966 · NIGMS · PRINCETON UNIVERSITY · PI TROYANSKAYA, OLGA G · 2005 to 2022
$6.4M
NIGMS NIH HHS R01 GM071966
6 · The paper itself

Abstract

Assays detecting blood transcriptome changes are studied for infectious disease diagnosis. Blood-based RNA alternative splicing (AS) events, which have not been well characterized in pathogen infection, have potential normalization and assay platform stability advantages over gene expression for diagnosis. Here, we present a computational framework for developing AS diagnostic biomarkers. Leveraging a large prospective cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and whole-blood RNA sequencing (RNA-seq) data, we identify a major functional AS program switch upon viral infection. Using an independent cohort, we demonstrate the improved accuracy of AS biomarkers for SARS-CoV-2 diagnosis compared with six reported transcriptome signatures. We then optimize a subset of AS-based biomarkers to develop microfluidic PCR diagnostic assays. This assay achieves nearly perfect test accuracy (61/62 = 98.4%) using a naive principal component classifier, significantly more accurate than a gene expression PCR assay in the same cohort. Therefore, our RNA splicing computational framework enables a promising avenue for host-response diagnosis of infection.

Indexed as

Communicable DiseasesCOVID-19Alternative SplicingBiomarkersCOVID-19 TestingHumansProspective StudiesRNASARS-CoV-2BiomarkersRNAdiagnostic biomarkerhost response assaysinfectious diseaseRNA splicingSARS-CoV-2viral infection

Identifiers

PMID36936082
PMCPMC10014279

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.