Journal of Molecular Diagnostics最新文献

Utility of a Multiplex Molecular Respiratory Pathogen Panel on Clinical Management of Children in the Pediatric Emergency Department. 多种分子呼吸道病原体小组在儿科急诊科儿童临床管理中的应用

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2026-05-04 DOI: 10.1016/j.jmoldx.2026.04.005

Samuel M Goodfellow, Jennifer Dien Bard, Vivian Lee, Deborah R Liu, Cristina Costales

{"title":"Utility of a Multiplex Molecular Respiratory Pathogen Panel on Clinical Management of Children in the Pediatric Emergency Department.","authors":"Samuel M Goodfellow, Jennifer Dien Bard, Vivian Lee, Deborah R Liu, Cristina Costales","doi":"10.1016/j.jmoldx.2026.04.005","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2026.04.005","url":null,"abstract":"Acute respiratory infections (ARI) in children contribute to a significant volume of Pediatric Emergency Department (PED) visits annually. Rapid molecular respiratory pathogen panels (RPPs) have increasingly been integrated in diagnostic workup. This study aims to investigate RPP impact on clinical management of children presenting to the PED and the effect of implementing restrictive criteria for RPP orders. Retrospective analysis of PED RPP orders between June 2023 through June 2024 was performed with a randomized subset of 400 patients in two cohorts (infants < 1 year old and children between 1 to 5 years old) selected for in depth chart abstraction including clinical presentation and management, with even distribution of RPP positive and negative patients. Of 2,052 RPPs performed from children age 5 or younger, 1,464 (71.3%) were positive for one or more targets. Regardless of RPP result or patient age, no significant differences in disease severity (mean Emergency Severity Index (ESI) 3.7 vs 3.7) or clinical management (infants, 5.5% and young children, 3%) were observed. Applying stewardship criteria retrospectively to both cohorts demonstrated potential 48% reduction in unnecessary testing by RPP. RPP results, positive or negative for one or more targets, had limited impact on clinical management in the PED. The data supports the potential value of stewardship intervention to reduce cost while maintaining critical pathogen identification.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive pathological and genetic investigation of four young adults with a short QT interval and sudden unexpected death. 4例青壮年QT间期短并发突发性死亡的病理学和遗传学综合分析。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2026-05-04 DOI: 10.1016/j.jmoldx.2026.04.004

Yukiko Hata, Yoshiaki Yamaguchi, Keiichi Hirono, Shojiro Ichimata, Koichi Mizumaki, Naoki Nishida

{"title":"Comprehensive pathological and genetic investigation of four young adults with a short QT interval and sudden unexpected death.","authors":"Yukiko Hata, Yoshiaki Yamaguchi, Keiichi Hirono, Shojiro Ichimata, Koichi Mizumaki, Naoki Nishida","doi":"10.1016/j.jmoldx.2026.04.004","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2026.04.004","url":null,"abstract":"While structural heart abnormalities are not typically associated with short QT syndrome (SQTS)-related sudden unexpected death, few autopsy studies have examined the underlying pathology and genetic factors of SQTS. Therefore, we conducted comprehensive pathological examinations and whole-exome sequencing in four men (aged 24, 28, 31, and 45 years) with sudden unexpected death and a short QT interval (sQT). No variants were identified in genes currently known to be associated with SQTS. An enrichment analysis was performed to identify potential genetic causes and mechanisms. None of the men had a history of cardiovascular disease, familial sudden death, or arrhythmia. Rare variants in SCN10A, ANK2, KCNQ2, and CACNA1H were detected, potentially associated with cardiac electrophysiology. One case showed apical hypertrophic cardiomyopathy with a rare PLEC variant. The other three showed left ventricular hypertrabeculation with poor compaction, deep recess formation, myocardial fibrosis, micronecrosis, and minimal inflammatory cell infiltration. The enrichment analysis showed that these variants were associated with cardiac electrophysiology and morphogenesis. These results showed that individuals with sQT may be at risk of sudden death even without a clinical or family history. This risk may be increased by cardiomyopathy-related gene variants in preclinical or early disease stages. Electrocardiographic evaluation to identify sQT cases followed by morphological and genetic evaluations improves the assessment of a sudden death risk in individuals with sQT.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Validation of MyHPVscore: a high-performance HPV ctDNA lab developed test. MyHPVscore的验证：一种高性能的HPV ctDNA实验室开发的测试。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2026-05-04 DOI: 10.1016/j.jmoldx.2026.04.003

Jordan Currie, Heather Walline, Colleen G Hochfelder, Chandan Bhambhani, Collin V Brummel, Erin Sandford, Apurva Bhangale, Rawan Akhdar, Marisa Buchakjian, Keith A Casper, Steven B Chinn, David Forner, Kelly M Malloy, Jennifer L Shah, Andrew G Shuman, Chaz L Stucken, Matthew E Spector, Francis P Worden, Pratyusha Yalamanchi, Molly Heft Neal, Paul L Swiecicki, Muneesh Tewari, Michelle L Mierzwa, Mark E Prince, J Chad Brenner

{"title":"Validation of MyHPVscore: a high-performance HPV ctDNA lab developed test.","authors":"Jordan Currie, Heather Walline, Colleen G Hochfelder, Chandan Bhambhani, Collin V Brummel, Erin Sandford, Apurva Bhangale, Rawan Akhdar, Marisa Buchakjian, Keith A Casper, Steven B Chinn, David Forner, Kelly M Malloy, Jennifer L Shah, Andrew G Shuman, Chaz L Stucken, Matthew E Spector, Francis P Worden, Pratyusha Yalamanchi, Molly Heft Neal, Paul L Swiecicki, Muneesh Tewari, Michelle L Mierzwa, Mark E Prince, J Chad Brenner","doi":"10.1016/j.jmoldx.2026.04.003","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2026.04.003","url":null,"abstract":"As rates of human papillomavirus-positive (HPV+) oropharynx cancer rise, there is increasing need for accurate biomarkers for diagnosis, treatment, and surveillance. The analytical performance of MyHPVscore, a droplet digital PCR laboratory-developed test (LDT), was characterized to detect circulating tumor DNA (ctDNA) from multiple high-risk HPV (hrHPV) types (16, 18, 31, 33, 35, 39) in plasma from patients with HPV+ cancer. Using Clinical and Laboratory Standards Institute guidelines, MyHPVscore was developed and validated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Analytical controls and plasma samples from HPV+ oropharyngeal squamous cell carcinoma (OPSCC) patients and non-cancer controls were used to evaluate sensitivity, specificity, linearity, and analyte stability. MyHPVscore demonstrated high analytical performance for detecting multiple hrHPV types. Limits of blank were 2.7 (HPV16) and 2.6 (other hrHPV types) positive droplets/reaction; limits of detection were 15.2 and 20.8 positive droplets/reaction, respectively. The linear range was 15-62,500 targets/mL plasma (HPV16) and 12-100,000 targets/mL (other hrHPV types) with strong correlation (R2 > 0.99). Analytes were stable for 96 hours at -20°C and yielded consistent qualitative results after >400 days of storage. No cross-reactivity was observed between hrHPV types or low-risk types (HPV6, HPV11). These results support the use of MyHPVscore as an LDT for detecting HPV+ oropharynx cancer. This methodology establishes an approach and standard controls that can benchmark other emerging ctDNA assays.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of Chimerism Testing by Next-Generation Sequencing Using Insertion/Deletion Markers: Analytical Validation and Examples of Clinical Utilization. 利用indel标记的下一代测序评价嵌合性测试：分析验证和临床应用实例。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2026-04-22 DOI: 10.1016/j.jmoldx.2026.04.002

Shannon Dutterer, Christle Moore, Maya Giddens, Juliet Smith, Jenifer Williams, Jessica Magwood, Jeane Silva, Cathi Murphey, Valia Bravo-Egana

{"title":"Evaluation of Chimerism Testing by Next-Generation Sequencing Using Insertion/Deletion Markers: Analytical Validation and Examples of Clinical Utilization.","authors":"Shannon Dutterer, Christle Moore, Maya Giddens, Juliet Smith, Jenifer Williams, Jessica Magwood, Jeane Silva, Cathi Murphey, Valia Bravo-Egana","doi":"10.1016/j.jmoldx.2026.04.002","DOIUrl":"10.1016/j.jmoldx.2026.04.002","url":null,"abstract":"Post-transplant engraftment monitoring is essential to assess the risk of complications after allogeneic hematopoietic transplantation, such as graft failure and disease relapse. It is based on the analysis of the percentage of chimerism detected in the recipient. Chimerism analysis has been routinely performed using short tandem repeats (STRs). Next-generation sequencing (NGS) has made possible the use of other genetic markers, such as single-nucleotide polymorphisms and insertions/deletions (indels). This study evaluated the performance characteristics of the NGStrack assay from GenDx to verify its accuracy, sensitivity, and reproducibility. It was determined that the assay can detect DNA contributed by donor and recipient within the range of 0.5% to 99.5%. The results of this assay were compared with an STR-based method, and examples of clinical utilization of the assay were provided using patient cases, including chimerism analysis on different cell subsets. It was confirmed that chimerism analysis using indel markers provides an increased sensitivity with respect to the reported sensitivity of assays using STR. The sensitivity for STR-based methods is in the range of 1% to 5%, whereas the sensitivity for the indel NGS-based method assessed here is 0.5%. The increased sensitivity and precise correlation between chimerism results with clinical events validates the usefulness of this assay for early diagnosis of disease relapse and graft failure and allows for more precise clinical management.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessment of Multiplex Molecular Tests for Detecting Viral Infections in Lower Respiratory Tract Specimens. 多重分子检测下呼吸道病毒感染的评估。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2026-04-22 DOI: 10.1016/j.jmoldx.2026.03.008

Giuseppe Sberna, Pierpaolo Paba, Cosmina Mija, Gaetana Costanza, Fabiano Brillo, Sandro Grelli, Fabrizio Maggi, Eleonora Lalle

{"title":"Assessment of Multiplex Molecular Tests for Detecting Viral Infections in Lower Respiratory Tract Specimens.","authors":"Giuseppe Sberna, Pierpaolo Paba, Cosmina Mija, Gaetana Costanza, Fabiano Brillo, Sandro Grelli, Fabrizio Maggi, Eleonora Lalle","doi":"10.1016/j.jmoldx.2026.03.008","DOIUrl":"10.1016/j.jmoldx.2026.03.008","url":null,"abstract":"Lower respiratory tract (LRT) infections represent a major cause of morbidity and mortality, particularly among critically ill patients. Rapid molecular diagnostic tests have improved the detection of respiratory pathogens; however, most commercial assays are validated exclusively in upper RT (URT) specimens, limiting their applicability in LRT samples, which are often more representative of disease in advanced or severe cases. This study evaluated the diagnostic performance of two commercially available assays, the BioFire Respiratory Panel 2.1 Plus and the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay, on bronchoalveolar lavage (BAL) specimens, using the Allplex Respiratory Panel 1/2/3 and the Allplex SARS-CoV-2 assay as reference methods validated both for URT and LRT matrices. A total of 132 BAL samples were analyzed. BioFire identified more positives than did Allplex, particularly for human rhinovirus/enterovirus (HRV/EV), human parainfluenza virus (HPIV), and non-severe acute respiratory syndrome coronavirus (SARS-CoV)-2 coronaviruses. The overall agreement between BioFire and Allplex was fair (κ = 0.237), and pathogen-specific concordance was almost perfect for SARS-CoV-2 (κ = 0.841), influenza A/B (κ = 0.808), and HPIV (κ = 0.884). The Panther assay showed substantial agreement with Allplex (κ = 0.719) and near-perfect concordance for SARS-CoV-2 and influenza viruses, while BioFire and Panther exhibited almost perfect interassay agreement (κ = 0.903). These findings demonstrate that assays validated for URT specimens can perform reliably on BAL samples, underlining the diagnostic potential of LRT matrices and the need for expanded validation of molecular respiratory panels across specimen types.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical-Grade Somatic Variant Interpretation Performance via a Rule-Constrained Large Language Model Framework (Oncology Logic-Informed Variant Evaluator). 基于规则约束的大语言模型框架（OLIVE）的临床级体细胞变异解释性能。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2026-04-22 DOI: 10.1016/j.jmoldx.2026.04.001

Melissa Y Tjota, Peng Wang, Sisi Qin, Ming Gao, Wenjun Kang, Viswateja Nelakuditi, Jeremy P Segal

{"title":"Clinical-Grade Somatic Variant Interpretation Performance via a Rule-Constrained Large Language Model Framework (Oncology Logic-Informed Variant Evaluator).","authors":"Melissa Y Tjota, Peng Wang, Sisi Qin, Ming Gao, Wenjun Kang, Viswateja Nelakuditi, Jeremy P Segal","doi":"10.1016/j.jmoldx.2026.04.001","DOIUrl":"10.1016/j.jmoldx.2026.04.001","url":null,"abstract":"Interpretation of somatic variants in clinical oncology requires integration of gene-specific biology, tumor context, and multiple evidence sources. Although large language models (LLMs) can assist variant interpretation, concerns remain regarding reproducibility, safety, and dependence on opaque model behavior. A rule-constrained LLM-based decision support framework, Oncology Logic-Informed Variant Evaluator (OLIVE), was developed and evaluated for somatic variant interpretation in a clinical molecular pathology service. OLIVE summarizes multiple data sources and applies explicit gene-specific guidance files to generate structured prompts for final classification and interpretation. Performance was assessed on 200 consecutive clinical tumor next-generation sequencing cases comprising 1437 variant observations (1228 unique variants). Concordance with historical laboratory classifications was evaluated for reportable (pathogenic/likely pathogenic) versus variant of uncertain significance determinations. Across three replicates, mean concordance with historical interpretation was 97.5% (range, 97.4% to 97.6%). Forty-two variants (2.9%) showed discordance in at least one replicate, with most discordances being consistent across runs. Blinded post hoc expert adjudication of discordant variants demonstrated interpretive variability favoring the laboratory or OLIVE classification in equal proportions (21 versus 21 variants). Discordances predominantly reflected intrinsic interpretive ambiguity, evidence evolution, and rule stringency rather than model instability. Similar results with a different LLM indicate performance is not model dependent and is primarily driven by expert guidance. These results indicate that OLIVE can reproducibly support expert somatic variant interpretation in a real-world clinical setting.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluating the Impact of ClinGen Variant Curation Expert Panel Criteria Specifications on Variant Interpretation across Multiple Genes. 评估ClinGen变异策展专家小组标准规范对跨多个基因变异解释的影响。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2026-04-15 DOI: 10.1016/j.jmoldx.2026.03.007

Dina Marek-Yagel, Rotem Greenberg, Michal Naftali, Shay Ben Shachar, Ofer Isakov

{"title":"Evaluating the Impact of ClinGen Variant Curation Expert Panel Criteria Specifications on Variant Interpretation across Multiple Genes.","authors":"Dina Marek-Yagel, Rotem Greenberg, Michal Naftali, Shay Ben Shachar, Ofer Isakov","doi":"10.1016/j.jmoldx.2026.03.007","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2026.03.007","url":null,"abstract":"Gene-specific variant interpretation guidelines are constantly being published to refine variant classification. The development, implementation, and benefit of such guidelines require careful assessment. This study evaluates the utility of these guidelines on variant interpretation. All actionable genes listed in American College of Medical Genetics and Genomics-Secondary findings version 3.3 genes with available Clinical Genome Resource (ClinGen) Variant Curation Expert Panel criteria specifications were analyzed. A total of 1223 variants in these genes were classified using the American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria and revised according to the Variant Curation Expert Panel specifications. Reclassification outcomes were compared using high-confidence variants. Application of the revised guidelines resulted in score changes in 63.1% of variants, although most did not cross classification thresholds. Reclassification occurred in 20.3% of cases, predominantly as downgrades and improved concordance with ClinVar by 5.8%, particularly for benign classifications. Of 622 variants of unknown significance (VUSs), 25.1% were resolved, with the highest resolution rates in BRCA1, BRCA2, and PALB2, whereas LDLR and TPM1 remained largely unchanged. No consistent correlation was found between the extent of criteria modification for each guideline and VUS resolution. The utility of the guidelines was shown to be variable and gene dependent. Although most reduced VUS rates and refined benign classifications, in some, only a minor impact was achieved, suggesting standardization and calibration of future guidelines are necessary.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oncogenicity Variant Interpreter: Oncogenicity Guidelines Implementation to Support Somatic Variants Interpretation in Precision Oncology. 致癌性变异解释器（OncoVI）：致癌性指南的实施，以支持精确肿瘤学中体细胞变异的解释。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2026-04-03 DOI: 10.1016/j.jmoldx.2026.03.004

Maria Giulia Carta, Lars Tögel, Annett Hölsken, Christoph Schubart, Heinrich Sticht, Robert Stöhr, Silvia Spoerl, Norbert Meidenbauer, Arndt Hartmann, Paolo Magni, Florian Haller, Fulvia Ferrazzi

{"title":"Oncogenicity Variant Interpreter: Oncogenicity Guidelines Implementation to Support Somatic Variants Interpretation in Precision Oncology.","authors":"Maria Giulia Carta, Lars Tögel, Annett Hölsken, Christoph Schubart, Heinrich Sticht, Robert Stöhr, Silvia Spoerl, Norbert Meidenbauer, Arndt Hartmann, Paolo Magni, Florian Haller, Fulvia Ferrazzi","doi":"10.1016/j.jmoldx.2026.03.004","DOIUrl":"10.1016/j.jmoldx.2026.03.004","url":null,"abstract":"Accurate and reproducible interpretation of somatic variants is fundamental for therapy decision-making in patients with cancer. To harmonize and automate oncogenicity classification, Oncogenicity Variant Interpreter (OncoVI), an open-source, Python-based implementation of the Clinical Genome Resource/Cancer Genomics Consortium/Variant Interpretation for Cancer Consortium oncogenicity guidelines, was developed. For each of the guideline criteria, the textual descriptions were interpreted, and publicly available resources were identified to be used as reference. Starting from the genomic coordinates of a variant, OncoVI automatically performs functional annotation, collects relevant evidence from the integrated resources, evaluates each criterion, and provides a final oncogenicity classification. OncoVI achieved an accuracy of 80% on a gold standard set of 93 somatic variants provided by the guidelines, with a sensitivity of 88% for oncogenic/likely oncogenic variants. When applied to a real-world set of 7802 variants from 557 participants previously evaluated by the Molecular Tumor Board (MTB) Erlangen, OncoVI showed 79% concordance with the prior MTB assessment of variant impact on protein function. In addition, expert reassessment of 135 MTB variants, conducted in accordance with the oncogenicity guidelines, further confirmed both the validity of OncoVI implementation and the appropriateness of the identified resources. Taken together, OncoVI provides significant support for the harmonized and reproducible oncogenicity classification of somatic variants across institutions.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Validation of a Low-Volume (100 μL) Plasma Protocol for HIV-1 RNA Quantification Using the Hologic Aptima HIV-1 Quant Dx Assay. Hologic Aptima HIV-1定量Dx检测低体积（100 μL）血浆方案的验证

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2026-04-03 DOI: 10.1016/j.jmoldx.2026.03.006

Lorna S Madurai, Kiveshan Reddy, Someshni Nair, Bhavani Manivannan, Kayla Pillay, Sharana Mahomed

{"title":"Validation of a Low-Volume (100 μL) Plasma Protocol for HIV-1 RNA Quantification Using the Hologic Aptima HIV-1 Quant Dx Assay.","authors":"Lorna S Madurai, Kiveshan Reddy, Someshni Nair, Bhavani Manivannan, Kayla Pillay, Sharana Mahomed","doi":"10.1016/j.jmoldx.2026.03.006","DOIUrl":"10.1016/j.jmoldx.2026.03.006","url":null,"abstract":"Pediatric HIV-1 viral load monitoring is often limited by the small blood volumes that can be safely obtained from infants and young children. Standard assays typically require 0.5 to 0.7 mL of plasma, which can pose challenges in these settings. This study evaluated a modified low-volume protocol using 100 μL of plasma, diluted for use with the Hologic Aptima HIV-1 Quant Dx assay, to determine whether performance was equivalent to the standard 700 μL protocol. An analytical validation was conducted by using de-identified EDTA plasma samples spanning a wide range of HIV-1 RNA concentrations. Each specimen was tested by using both protocols on the Panther system. Agreement between methods was assessed by using log10 differences, correlation analysis, and Bland-Altman analysis; within-run and between-run precision was evaluated by using replicate testing of negative, low-positive, and high-positive samples. The 100 μL protocol displayed excellent concordance with the standard method, with a mean log10 difference of approximately 0.00 and a maximum difference of 0.12 log10 copies/mL. No false-positive or false-negative results were observed among 30 fully suppressed samples. Precision analyses showed minimal variability, with all results within predefined acceptability criteria. These findings indicate that the low-volume Aptima protocol provides accurate and reliable HIV-1 RNA quantification and can expand access to viral load testing in pediatric patients and other clinical settings in which plasma volume is limited.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Certified Reference Materials for Standardization of Cell-Free DNA Isolation Recovery in Liquid Biopsy. 液体活检中cfDNA分离回收标准化标准物质。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2026-04-03 DOI: 10.1016/j.jmoldx.2026.03.005

Sumeyra Nur Sanal Demirci, Sema Tiryaki, Muslum Akgoz

{"title":"Certified Reference Materials for Standardization of Cell-Free DNA Isolation Recovery in Liquid Biopsy.","authors":"Sumeyra Nur Sanal Demirci, Sema Tiryaki, Muslum Akgoz","doi":"10.1016/j.jmoldx.2026.03.005","DOIUrl":"10.1016/j.jmoldx.2026.03.005","url":null,"abstract":"Reliable quantification of cell-free DNA (cfDNA) in liquid biopsy diagnostics critically depends on unbiased and reproducible isolation workflows. Fragment-length-dependent recovery during isolation represents a major source of pre-analytical bias. This variability limits method validation, interlaboratory comparability, and the reliability of cfDNA measurements in clinical and research laboratories. However, certified reference materials (CRMs) specifically designed to evaluate cfDNA isolation recovery are currently lacking. In this study, two synthetic cfDNA CRMs were developed to enable fragment-length-resolved assessment of isolation recovery. UME CRM 3022 comprises 80- and 240-bp double-stranded DNA fragments, whereas UME CRM 3024 includes fragments of 80, 120, 160, and 240 bp. The materials were prepared gravimetrically and characterized using optimized duplex and multiplex droplet digital PCR assays. Homogeneity, short-term stability, and long-term stability were evaluated. Certified copy number concentrations with stated measurement uncertainties were assigned for each fragment. Applicability in a plasma matrix was demonstrated to support practical workflow integration. These CRMs provide a traceable, fragment-resolved framework for recovery-based standardization of cfDNA isolation, supporting improved analytical reliability in liquid biopsy applications.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0