Evidence map›Paper›PMID 40082566›Full record

Trial reportScientific reports2025

Exome sequencing shows same pattern of clonal tumor mutational burden, intratumor heterogenicity and clonal neoantigen between autologous tumor and Vigil product.

David Willoughby, Ernest Bognar, Laura Stanbery, Casey Nagel, Gladice Wallraven, Aman Pruthi, Nicholas Bild, Ericca Stamper, Donald Rao, Adam Walter and 1 more

Abstract readClinical Trial, Phase II
In one paragraph

Trial report in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
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

11 authors.

David WilloughbyFrontage Laboratories, Inc, Deerfield Beach, FL, USA.
Ernest BognarGradalis, Inc, 2545 Golden Bear Dr., Suite 110, Carrollton, Dallas, TX, 75006, USA.
Laura StanberyGradalis, Inc, 2545 Golden Bear Dr., Suite 110, Carrollton, Dallas, TX, 75006, USA.
Casey NagelFrontage Laboratories, Inc, Deerfield Beach, FL, USA.
Gladice WallravenGradalis, Inc, 2545 Golden Bear Dr., Suite 110, Carrollton, Dallas, TX, 75006, USA.
Aman PruthiFrontage Laboratories, Inc, Deerfield Beach, FL, USA.
Nicholas BildFrontage Laboratories, Inc, Deerfield Beach, FL, USA.
Ericca StamperFrontage Laboratories, Inc, Deerfield Beach, FL, USA.
Donald RaoGradalis, Inc, 2545 Golden Bear Dr., Suite 110, Carrollton, Dallas, TX, 75006, USA.
Adam WalterGradalis, Inc, 2545 Golden Bear Dr., Suite 110, Carrollton, Dallas, TX, 75006, USA.
John NemunaitisGradalis, Inc, 2545 Golden Bear Dr., Suite 110, Carrollton, Dallas, TX, 75006, USA. Johnnemunaitis@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Retrospective data support overall survival (OS) advantage to high clonal tumor mutation burden (cTMB), high clonal neoantigen load (cNEO) and low intratumor heterogeneity (ITH) in cancer patients who receive immunotherapy. In order to explore this relationship prospectively with Vigil, a triple function targeted immunotherapy involving ovarian cancer patients in long term follow up of the Phase 2b VITAL trial, we developed an exome sequencing procedure and associated bioinformatics pipeline to determine clonal signal patterns. DNA libraries containing exome sequences tagged with unique molecular identifiers (UMI) were prepared from paired samples and sequenced on Illumina sequencers to high coverage depths of ~ 930X (tumor) and ~ 130X (normal). Raw sequence reads were processed into optimized binary alignment map (BAM) files, using the UMI information. The BAM files were inputted into modules for calling MHC-I alleles, annotating single nucleotide variants (SNVs) and small insertions/deletions (InDels), and for determination of allelic copy number. The outputs were used to predict the sequence of peptide neoantigens and to perform clonality analysis in order to assign each SNV and InDel in a patient tumor sample to a primary clone or subclone. The Clonal Neoantigen pipeline was further assessed using whole exome Illumina sequencing data from three previously published studies. Evaluation of the pipeline using synthetic sequencing data from a sub-clonal deconvolution tool benchmarking study, showed positive predictive value (PPV) and positive percent agreement (PPA) of > 97.5% and > 96.5%, respectively, for SNV and InDel detection with minimum requirements for variant density and allele fraction. Haplotype calls from the Clonal Neoantigen pipeline MHC-I/ MHC-II typing module matched a published benchmark for 91.5% of the calls in a sample of 99 patients. Analysis of exome sequencing data from 14 patients with advanced melanoma revealed a strong correlation between cTMB values determined by the Clonal Neoantigen pipeline as compared to those calculated from the published data (R

Indexed as

Antigens, NeoplasmExomeExome SequencingMutationNeoplasmsOvarian NeoplasmsFemaleHigh-Throughput Nucleotide SequencingHumansImmunotherapyAntigens, NeoplasmAutologous tumorClonal tumor mutation burdenIntratumor heterogeneityNeoantigenTumor mutation burdenVigil

Identifiers

PMID40082566
PMCPMC11906592

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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.