Abstract 7179: Streamlined Glioma diagnosis from formalin-fixed paraffin-embedded (FFPE) tissue: One assay, a fraction of the cost and turnaround time
Notice bibliographique
Résumé
Abstract We developed a single diagnostic assay to detect Glioma biomarkers including whole chromosomal and gene copy number variations (CNVs), and single nucleotide variations (SNVs). CNVs and SNVs are traditionally detected using different large/high-throughput platforms that can only exist in big genomic facilities. This leads to very high molecular costs and long turnaround times. The current complex diagnostic algorithm creates delays in patient management while increasing inequity in healthcare as smaller non-centralized labs are unable to conduct glioma molecular testing. To streamline glioma diagnosis and address these challenges, we aimed to use a third-generation sequencing platform called nanopore sequencing. It can simultaneously detect both CNVs and SNVs using small inexpensive tools, but is not yet compatible with formalin-fixed paraffin-embedded (FFPE) DNA. Therefore, we developed a PCR based assay to create clean nanopore compatible FFPE DNA copies to detect CNVs and SNVs. We established a single nucleotide polymorphism (SNP) microarray-based approach to detect the CNVs. Approximately 300 amplicons were included in the assay design including unique SNP-rich areas to detect the chromosomal heterozygosity. We included all glioma markers required by World Health Organization's (WHO) guidelines including chromosomal CNVs on chr 1, 7, 10, 19; gene CNVs on CDKN2A, CDKN2B, EGFR; and SNVs on IDH1, IDH2, TERT promoter, TP53, ATRX, H3-3A and H3C2. We optimized the testing conditions, and reduced cost and turn-around including streamlining the data analysis using a custom shell script. Lastly, we conducted a mini validation as well as a cost and turn-around time analysis using 40 Glioma FFPE samples. All our samples had a concordant molecular classification status with the reference results. The concordance, sensitivity and specificity (total accuracy) of the assay were all at 100%. A loss status of chr 1p, chr 19q and chr 10 were determined via a loss of heterozygosity (LOH), and gain status of chr 7 was observed as an allele gain 2:1 SNP pattern. Our total turnaround time (from DNA extraction to data analysis) is 3 business days for an entire batch of samples, which is at least 1/3rd the turnaround time of conventional methods. Our material cost is $150 CAD/sample (including DNA extraction, library preparation and sequencing) which is ∼10% of the existing assay costs. This is the first single streamlined diagnostic test to detect CNVs and SNVs in Gliomas using FFPE DNA. Our assay will increase healthcare equity by allowing smaller labs to adopt molecular testing due to its low assay/capital cost, shorter testing time, and streamlined workflow, helping to overcome many of the existing cancer diagnostic challenges. Citation Format: Mashiat Lamia Mimosa, Jared T. Simpson, Shreya Patel, Karel Boissinot, Mora Tiab, Ramzi Fattouh, Rola M. Saleeb. Streamlined Glioma diagnosis from formalin-fixed paraffin-embedded (FFPE) tissue: One assay, a fraction of the cost and turnaround time [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7179.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,003 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».