Evidence map›Paper›PMID 40980342›Full record

ArticleThe journal of liquid biopsy2025

Validation of a liquid biopsy assay with increased sensitivity for clinical comprehensive genomic profiling.

Xavier S Bower, Jan Wignall, Matthew G Varga, Joyce Zhu, Michael O'Sullivan, Naomi E Searle, Lenny K Hong, Turgut Dogruluk, Zeqian Li, Tiffany E Farmer and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of liquid biopsy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

20 authors.

Xavier S BowerBillionToOne, Inc., Menlo Park, CA, USA.
Jan WignallBillionToOne, Inc., Menlo Park, CA, USA.
Matthew G VargaBillionToOne, Inc., Menlo Park, CA, USA.
Joyce ZhuBillionToOne, Inc., Menlo Park, CA, USA.
Michael O'SullivanBillionToOne, Inc., Menlo Park, CA, USA.
Naomi E SearleBillionToOne, Inc., Menlo Park, CA, USA.
Lenny K HongBillionToOne, Inc., Menlo Park, CA, USA.
Turgut DogrulukBillionToOne, Inc., Menlo Park, CA, USA.
Zeqian LiBillionToOne, Inc., Menlo Park, CA, USA.
Tiffany E FarmerBillionToOne, Inc., Menlo Park, CA, USA.
Emilio Rosas-LinhardBillionToOne, Inc., Menlo Park, CA, USA.
Jason LuongBillionToOne, Inc., Menlo Park, CA, USA.
Esther LinBillionToOne, Inc., Menlo Park, CA, USA.
Marie Erica SimonBillionToOne, Inc., Menlo Park, CA, USA.
David S TsaoBillionToOne, Inc., Menlo Park, CA, USA.
John R Ten BoschBillionToOne, Inc., Menlo Park, CA, USA.
Gary PalmerBillionToOne, Inc., Menlo Park, CA, USA.
Ajeet GajraHematology Oncology Associates of Central NY, East Syracuse, NY, USA.
Chanh HuynhCancer Care Associates of York, York, PA, USA.
Wen ZhouBillionToOne, Inc., Menlo Park, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent advancements in precision oncology have affirmed the need for comprehensive genomic profiling (CGP) liquid biopsy assays with increased sensitivity, especially for detecting alterations in tumors which shed circulating tumor DNA (ctDNA) at low abundance. Such tests could address the limitations of tissue biopsies while simultaneously enhancing the detection of clinically actionable variants. This study included analytical and clinical validation studies of Northstar Select, a plasma-based, tumor-naive CGP assay covering 84 genes. The assay detects SNV/Indels, CNVs (gain and loss), fusions, and microsatellite instability (MSI-H). A retrospective analysis of 674 analytical patient samples collected during routine care in the United States, covering various solid tumor types, was conducted to investigate performance across tumor types. In addition, clinical validation was conducted in a prospective head-to-head comparison study of 182 patients, assessing the performance of Northstar Select and on-market CGP liquid biopsy assays. Analytical validation demonstrated a 95 % Limit of Detection of 0.15 % variant allele frequency (VAF) for SNV/Indels, which was confirmed by digital droplet PCR. Northstar Select demonstrated sensitive detection of CNVs in liquid down to 2.11 copies for amplifications and 1.80 copies for losses, and 0.30 % for gene fusions, addressing a key challenge in liquid biopsy testing. It outperformed on-market CGP assays, identifying 51 % more pathogenic SNV/indels and 109 % more CNVs. Additionally, this resulted in 45 % fewer null reports with no pathogenic or actionable results. The majority (91 %) of additional clinically actionable SNV/indels found were detected below 0.5 % VAF. Northstar Select demonstrated analytical and clinical validity, with high sensitivity across all variant classes. The low LOD allows for reliable detection of variants at lower VAFs compared to existing commercial assays. Northstar Select can therefore enhance clinical decision-making by providing the opportunity to identify more actionable genomic alterations, which may be especially beneficial for patients with low-shedding tumors.

Indexed as

Circulating tumor DNAComprehensive genomic profilingLiquid biopsyNext generation sequencingPrecision oncology

Identifiers

PMID40980342
PMCPMC12447423

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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.