Evidence map›Paper›PMID 30742071›Full record

ArticleNature microbiology2019

Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease.

Timothy A Blauwkamp, Simone Thair, Michael J Rosen, Lily Blair, Martin S Lindner, Igor D Vilfan, Trupti Kawli, Fred C Christians, Shivkumar Venkatasubrahmanyam, Gregory D Wall and 13 more

2 registry-linked trialsAbstract readValidation Study
PubMed Publisher
In one paragraph

Article in Nature microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 560 papers.

0numbers the graph read from it
0cells of the map it votes in
560citing papers in PubMed
37.7field-weighted citation impact, top 1% 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.

NCT04047719 completednot on this map

Pneumonia in the ImmunoCompromised - Use of the Karius Test for the Detection of Undiagnosed Pathogens

TypeobservationalSponsorKarius, Inc.Ran2019 to 2022Enrolled257ConditionsPneumonia, Bacterial, Pneumonia, Viral, Pneumonia Fungal, Pneumonia CavitaryArmsKarius Test
NCT07626073 enrolling by invitationnot on this mapstarted 2023, after this paper: background citation

h Can Provide the Detection Results of Pathogen Type and Resistant Gene. This Study is a Prospective Multi Centers Study to Explore Using the New Diagnostic Tool of " RPIP " and the Different Detection Methods of Next Generation Sequencing and Multiplex PC R in Patients With Pneumonia in ICU. Further Compare the Difference of Pathogen Identification and Clinical Impact by Different Diagnostic Methods.

Typeobservational_patient_registrySponsorChina Medical University HospitalRan2023 to 2028Enrolled200ConditionsRespiratory Pathogens
3 · Its place in the literature

Who cites it

560 citing papers in PubMed, 942 citations in OpenAlex.

  1. Trial
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  11. Detection ofASM case reports · 2026
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  18. [Clinical value of cerebrospinal fluid metagenomic next-generation sequencing in the diagnosis of neonatal intracranial infection].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026
    Observational
  19. Article
  20. Article

500 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 2 institutions in 1 country.

Timothy A Blauwkamp *Karius, Inc., Redwood City, CA, USA. tim.blauwkamp@kariusdx.com.ORCID http://orcid.org/0000-0003-2790-4256
Simone Thair *Department of Emergency Medicine, Stanford University, Palo Alto, CA, USA.
Michael J RosenKarius, Inc., Redwood City, CA, USA.
Lily BlairKarius, Inc., Redwood City, CA, USA.
Martin S LindnerKarius, Inc., Redwood City, CA, USA.
Igor D VilfanKarius, Inc., Redwood City, CA, USA.
Trupti KawliKarius, Inc., Redwood City, CA, USA.
Fred C ChristiansKarius, Inc., Redwood City, CA, USA.
Shivkumar VenkatasubrahmanyamKarius, Inc., Redwood City, CA, USA.
Gregory D WallKarius, Inc., Redwood City, CA, USA.
Anita CheungKarius, Inc., Redwood City, CA, USA.
Zoë N RogersKarius, Inc., Redwood City, CA, USA.
Galit Meshulam-SimonKarius, Inc., Redwood City, CA, USA.
Liza HuijseKarius, Inc., Redwood City, CA, USA.
Sanjeev BalakrishnanKarius, Inc., Redwood City, CA, USA.
James V QuinnDepartment of Emergency Medicine, Stanford University, Palo Alto, CA, USA.
Desiree HollemonKarius, Inc., Redwood City, CA, USA.ORCID http://orcid.org/0000-0003-4971-9334
David K HongKarius, Inc., Redwood City, CA, USA.
Marla Lay VaughnKarius, Inc., Redwood City, CA, USA.
Mickey KerteszKarius, Inc., Redwood City, CA, USA.
Sivan BercoviciKarius, Inc., Redwood City, CA, USA.
Judith C Wilber *Karius, Inc., Redwood City, CA, USA.
Samuel Yang *Department of Emergency Medicine, Stanford University, Palo Alto, CA, USA.
Stanford University · USFresenius Medical Care (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Thousands of pathogens are known to infect humans, but only a fraction are readily identifiable using current diagnostic methods. Microbial cell-free DNA sequencing offers the potential to non-invasively identify a wide range of infections throughout the body, but the challenges of clinical-grade metagenomic testing must be addressed. Here we describe the analytical and clinical validation of a next-generation sequencing test that identifies and quantifies microbial cell-free DNA in plasma from 1,250 clinically relevant bacteria, DNA viruses, fungi and eukaryotic parasites. Test accuracy, precision, bias and robustness to a number of metagenomics-specific challenges were determined using a panel of 13 microorganisms that model key determinants of performance in 358 contrived plasma samples, as well as 2,625 infections simulated in silico and 580 clinical study samples. The test showed 93.7% agreement with blood culture in a cohort of 350 patients with a sepsis alert and identified an independently adjudicated cause of the sepsis alert more often than all of the microbiological testing combined (169 aetiological determinations versus 132). Among the 166 samples adjudicated to have no sepsis aetiology identified by any of the tested methods, sequencing identified microbial cell-free DNA in 62, likely derived from commensal organisms and incidental findings unrelated to the sepsis alert. Analysis of the first 2,000 patient samples tested in the CLIA laboratory showed that more than 85% of results were delivered the day after sample receipt, with 53.7% of reports identifying one or more microorganisms.

Indexed as

Cell-Free Nucleic AcidsCohort StudiesCommunicable DiseasesDNA, BacterialDNA, FungalDNA, ViralHigh-Throughput Nucleotide SequencingHumansSepsisCell-Free Nucleic AcidsDNA, BacterialDNA, FungalDNA, Viral

Identifiers

PMID30742071
OpenAlexW2911798461

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.