Evidence map›Paper›PMID 34562627›Full record

ArticleInternational journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases2021

Characterizing the molecular composition and diagnostic potential of Mycobacterium tuberculosis urinary cell-free DNA using next-generation sequencing.

Amy Oreskovic, Adam Waalkes, Elizabeth A Holmes, Christopher A Rosenthal, Douglas P K Wilson, Adrienne E Shapiro, Paul K Drain, Barry R Lutz, Stephen J Salipante

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Article in International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2021. 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.

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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

9 authors.

Amy OreskovicDepartment of Bioengineering, University of Washington, Seattle, Washington, USA.
Adam WaalkesDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Elizabeth A HolmesDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Christopher A RosenthalDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Douglas P K WilsonUmkhuseli Innovation and Research Management, Pietermaritzburg, South Africa; Edendale Hospital, University of KwaZulu-Natal, Pietermaritzburg, South Africa.
Adrienne E ShapiroDepartment of Medicine, University of Washington, Seattle, Washington, USA; Department of Global Health, University of Washington, Seattle, Washington, USA.
Paul K DrainDepartment of Medicine, University of Washington, Seattle, Washington, USA; Department of Global Health, University of Washington, Seattle, Washington, USA.
Barry R LutzDepartment of Bioengineering, University of Washington, Seattle, Washington, USA; Brotman Baty Institute for Precision Medicine, Seattle, Washington, USA.
Stephen J SalipanteDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA; Brotman Baty Institute for Precision Medicine, Seattle, Washington, USA. Electronic address: stevesal@uw.edu.

Funding

Novel clinic-based TB diagnostics and testing algorithms for persons with HIVK23AI140918 · NIAID · UNIVERSITY OF WASHINGTON · PI SHAPIRO, ADRIENNE E · 2019 to 2024
$937k
NIAID NIH HHS K23 AI140918
6 · The paper itself

Abstract

backgroundUrine cell-free DNA (cfDNA) is an attractive target for diagnosing pulmonary Mycobacterium tuberculosis (MTB) infection, but has not been thoroughly characterized as a biomarker.

methodsThis study was performed to investigate the size and composition of urine cfDNA from tuberculosis (TB) patients with minimal bias using next-generation sequencing (NGS). A combination of DNA extraction and single-stranded sequence library preparation methods demonstrated to recover short, highly degraded cfDNA fragments was employed. Urine cfDNA from 10 HIV-positive patients with pulmonary TB and two MTB-negative controls was examined.

resultsMTB-derived cfDNA was identifiable by NGS from all MTB-positive patients and was absent from negative controls. MTB cfDNA was significantly shorter than human cfDNA, with median fragment lengths of ≤19-52 bp and 42-92 bp, respectively. MTB cfDNA abundance increased exponentially with decreased fragment length, having a peak fragment length of ≤19 bp in most samples. In addition, we identified a larger fraction of short human genomic cfDNA, ranging from 29 to 53 bp, than previously reported. Urine cfDNA fragments spanned the MTB genome with relative uniformity, but nucleic acids derived from multicopy elements were proportionately over-represented.

conclusionsTB urine cfDNA is a potentially powerful biomarker but is highly fragmented, necessitating special procedures to maximize its recovery and detection.

Indexed as

Cell-Free Nucleic AcidsMycobacterium tuberculosisBiomarkersDNA, BacterialHigh-Throughput Nucleotide SequencingHumansTuberculosis, PulmonaryBiomarkersCell-Free Nucleic AcidsDNA, BacterialCell-free DNADiagnosticsDNA sequencingMolecular diagnosisMycobacterium tuberculosisTransrenal DNAUrine

Identifiers

PMID34562627
PMCPMC8627387

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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.