Evidence map›Paper›PMID 31053596›Full record

ArticleThe EMBO journal2019

Phospho-RNA-seq: a modified small RNA-seq method that reveals circulating mRNA and lncRNA fragments as potential biomarkers in human plasma.

Maria D Giraldez, Ryan M Spengler, Alton Etheridge, Annika J Goicochea, Missy Tuck, Sung Won Choi, David J Galas, Muneesh Tewari

Abstract readValidation Study
In one paragraph

Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing 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

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

  1. Pooled it
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  12. Epitranscriptomic sculpting: the role of mMedical oncology (Northwood, London, England) · 2025
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11 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

8 authors.

Maria D GiraldezDepartment of Internal Medicine, Hematology/Oncology Division, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-6829-7603
Ryan M SpenglerDepartment of Internal Medicine, Hematology/Oncology Division, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-0181-5589
Alton EtheridgePacific Northwest Research Institute, Seattle, WA, USA.
Annika J GoicocheaDepartment of Internal Medicine, Hematology/Oncology Division, University of Michigan, Ann Arbor, MI, USA.
Missy TuckDepartment of Internal Medicine, Hematology/Oncology Division, University of Michigan, Ann Arbor, MI, USA.
Sung Won ChoiDepartment of Pediatrics, Hematology/Oncology Division, University of Michigan, Ann Arbor, MI, USA.
David J GalasPacific Northwest Research Institute, Seattle, WA, USA.ORCID 0000-0001-8248-8617
Muneesh TewariDepartment of Internal Medicine, Hematology/Oncology Division, University of Michigan, Ann Arbor, MI, USA mtewari@med.umich.edu.ORCID 0000-0002-7781-3152

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
Training Program in Molecular HematologyT32HL007622 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SUNG WON CHOI, Jordan A. Shavit · 1986 to 2026
$9.2M
Reference Profiles of Extracellular RNA in 4 Body Fluids of Healthy HumansU01HL126496 · NHLBI · PACIFIC NORTHWEST RESEARCH INSTITUTE · PI GALAS, DAVID J., NICKERSON, DEBORAH A · 2014 to 2018
$3.5M
Reference Profiles of ExRNA in Biofluids from Well-Defined Human CohortsU01HL126499 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TEWARI, MUNEESH · 2014 to 2018
$3.3M
NCI NIH HHS P30 CA046592NHLBI NIH HHS T32 HL007622NHLBI NIH HHS U01 HL126496NHLBI NIH HHS U01 HL126499
6 · The paper itself

Abstract

Extracellular RNAs (exRNAs) in biofluids have attracted great interest as potential biomarkers. Although extracellular microRNAs in blood plasma are extensively characterized, extracellular messenger RNA (mRNA) and long non-coding RNA (lncRNA) studies are limited. We report that plasma contains fragmented mRNAs and lncRNAs that are missed by standard small RNA-seq protocols due to lack of 5' phosphate or presence of 3' phosphate. These fragments were revealed using a modified protocol ("phospho-RNA-seq") incorporating RNA treatment with T4-polynucleotide kinase, which we compared with standard small RNA-seq for sequencing synthetic RNAs with varied 5' and 3' ends, as well as human plasma exRNA Analyzing phospho-RNA-seq data using a custom, high-stringency bioinformatic pipeline, we identified mRNA/lncRNA transcriptome fingerprints in plasma, including tissue-specific gene sets. In a longitudinal study of hematopoietic stem cell transplant patients, bone marrow- and liver-enriched exRNA genes were tracked with bone marrow recovery and liver injury, respectively, providing proof-of-concept validation as a biomarker approach. By enabling access to an unexplored realm of mRNA and lncRNA fragments, phospho-RNA-seq opens up new possibilities for plasma transcriptomic biomarker development.

Indexed as

BiomarkersBlood Chemical AnalysisCell-Free Nucleic AcidsComputational BiologyGene Expression ProfilingHumansMicroRNAsRNA, Long NoncodingRNA, MessengerRNA-SeqSequence Analysis, RNABiomarkersCell-Free Nucleic AcidsMicroRNAsRNA, Long NoncodingRNA, Messengercell‐free RNAextracellular RNAliquid biopsyRNA‐seq

Identifiers

PMID31053596
PMCPMC6545557

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.