Journal of Molecular Diagnostics最新文献_第10页

Analytical Performance of the NCI-myeloMATCH Assay NCI-myeloMATCH测定的分析性能-一种髓系疾病的快速周转基因组分析测定。

IF 3.4 3区医学 Q1 PATHOLOGY

Journal of Molecular Diagnostics

Pub Date : 2025-05-15 DOI: 10.1016/j.jmoldx.2025.05.001

Cecilia C.S. Yeung , Srikrishna K. Narava , Ting-Chia Chang , Maria Saeed , Lauri Aicher , Lan W. Beppu , Marvin S. Majano , Erin M. Taylor , Corinne E. Camalier , Pooja Sandhuria , Olga Sala-Torra , Jessica Li , Laura M. Yee , Lisa M. McShane , Chris Karlovich , Richard F. Little , Lyndsay Harris , James H. Doroshow , Paul M. Williams , Jerald P. Radich , Shahanawaz Jiwani

myeloMATCH is a National Cancer Institute (NCI) precision medicine clinical trial initiative to evaluate treatments for acute myeloid leukemia and myelodysplastic syndrome based on a leukemia’s diagnostic molecular–genetic profile. The NCI myeloid assay version 2 (NMAv2) uses the Genexus System, an automated platform with <48-hour turnaround from specimen receipt to reporting, to provide harmonized regulatory-compliant use for myeloMATCH across two independent clinical laboratories. Using clinical specimens, cell lines, and contrived reference materials, NMAv2 exhibited 99% sensitivity for 291 known mutations and 100% specificity. High reproducibility detecting all reportable variants was observed, with >98% mean positive percentage agreement and 100% negative percent agreement across six reproducibility assessments. Reproducibility experiments of companion diagnostic biomarkers (1 to 1.5× clinical limit of reporting) showed 100% positive percentage agreement and negative percent agreement. The limit of detection was 0.06% for hotspot single-nucleotide variants, 0.16% for non-hotspot single-nucleotide variants, 0.51% for hotspot insertion/deletions, approximately 1% for non-hotspot insertion/deletions, 0.23% for FLT3–internal tandem duplications, and ≤40 reads at 0.1% tumor content for fusions. Concordance of 99.39% was observed in orthogonal assays testing 76 blinded myeloid specimens in the sensitivity study, and 100% concordance was observed in testing 54 FLT3–internal tandem duplication specimens. The results show that NMAv2 has high specificity, sensitivity, accuracy, and reproducibility, and can rapidly characterize genomic alterations in acute myeloid leukemia and myelodysplastic syndrome.

MyeloMATCH是美国国家癌症研究所（NCI）的一项精准医学临床试验计划，旨在根据患者的诊断、临床和遗传特征来评估急性髓性白血病（AML）和骨髓增生异常综合征（MDS）的治疗方法。NCI髓系测定v2 （NMAv2）使用Ion Torrent Genexus系统，这是一个自动化平台，从标本接收到报告的周期小于48小时，为两个独立的临床实验室提供符合法规的使用，并具有统一的工作流程。使用骨髓抽吸液或外周血临床标本、细胞系和人造参照物，NMAv2对291个已知突变的敏感性为99%，特异性为100%。检测所有可报告的变异观察到高再现性，在六次再现性评估中，平均阳性百分比一致性（PPA）为bb0 98%，阴性百分比一致性（NPA）为100%。伴随诊断生物标志物（1-1.5倍临床LOR）的重复性实验显示PPA和NPA 100%。热点snv的检出限为0.06%，非热点snv的检出限为0.16%，热点索引的检出限为0.51%，非热点索引的检出限为~ 1%，FLT3-ITDs的检出限为0.23%，融合体在0.1%肿瘤含量下≤40 reads。在敏感性研究中，76例盲法髓系标本的正交试验的一致性为99.39%，54例FLT3-ITD标本的一致性为100%。结果表明，NMAv2具有高特异性、敏感性、准确性和可重复性，可以快速表征AML和MDS的基因组改变。

{"title":"Analytical Performance of the NCI-myeloMATCH Assay","authors":"Cecilia C.S. Yeung , Srikrishna K. Narava , Ting-Chia Chang , Maria Saeed , Lauri Aicher , Lan W. Beppu , Marvin S. Majano , Erin M. Taylor , Corinne E. Camalier , Pooja Sandhuria , Olga Sala-Torra , Jessica Li , Laura M. Yee , Lisa M. McShane , Chris Karlovich , Richard F. Little , Lyndsay Harris , James H. Doroshow , Paul M. Williams , Jerald P. Radich , Shahanawaz Jiwani","doi":"10.1016/j.jmoldx.2025.05.001","DOIUrl":"10.1016/j.jmoldx.2025.05.001","url":null,"abstract":"<div><div>myeloMATCH is a National Cancer Institute (NCI) precision medicine clinical trial initiative to evaluate treatments for acute myeloid leukemia and myelodysplastic syndrome based on a leukemia’s diagnostic molecular–genetic profile. The NCI myeloid assay version 2 (NMAv2) uses the Genexus System, an automated platform with <48-hour turnaround from specimen receipt to reporting, to provide harmonized regulatory-compliant use for myeloMATCH across two independent clinical laboratories. Using clinical specimens, cell lines, and contrived reference materials, NMAv2 exhibited 99% sensitivity for 291 known mutations and 100% specificity. High reproducibility detecting all reportable variants was observed, with >98% mean positive percentage agreement and 100% negative percent agreement across six reproducibility assessments. Reproducibility experiments of companion diagnostic biomarkers (1 to 1.5× clinical limit of reporting) showed 100% positive percentage agreement and negative percent agreement. The limit of detection was 0.06% for hotspot single-nucleotide variants, 0.16% for non-hotspot single-nucleotide variants, 0.51% for hotspot insertion/deletions, approximately 1% for non-hotspot insertion/deletions, 0.23% for <em>FLT3</em>–internal tandem duplications, and ≤40 reads at 0.1% tumor content for fusions. Concordance of 99.39% was observed in orthogonal assays testing 76 blinded myeloid specimens in the sensitivity study, and 100% concordance was observed in testing 54 <em>FLT3</em>–internal tandem duplication specimens. The results show that NMAv2 has high specificity, sensitivity, accuracy, and reproducibility, and can rapidly characterize genomic alterations in acute myeloid leukemia and myelodysplastic syndrome.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 8","pages":"Pages 783-795"},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095415","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 Bioinformatician Body of Knowledge—Clinical Laboratory Regulation and Data Security Core 临床生物信息学家知识体系-临床实验室法规和数据安全核心：分子病理学协会的报告。

IF 3.4 3区医学 Q1 PATHOLOGY

Journal of Molecular Diagnostics

Pub Date : 2025-05-08 DOI: 10.1016/j.jmoldx.2025.04.003

Ryan J. Schmidt , Larissa V. Furtado , Amber M. Fussell , Danielle Jordan , Matthew Lebo , Aijazuddin Syed , Robyn L. Temple-Smolkin , Eric Venner , Elizabeth Worthey , Alexis B. Carter

Clinical bioinformaticians have come to play an essential role in clinical molecular diagnostic laboratories. However, the core knowledge needed for the clinical practice and training of this emerging group of professionals has not been previously established. Clinical laboratories are subject to a complex set of legal and accreditation requirements from numerous governmental and nongovernmental bodies that cover the generation, processing, storage, and distribution of patient data in the form of test results and intermediate data files. Clinical bioinformaticians are intimately involved in the development and maintenance of systems that perform these activities. This third article in the Association for Molecular Pathology's Clinical Bioinformatician Body of Knowledge Core series presents a body of knowledge for the clinical bioinformatician describing relevant laboratory regulations and data security in the domains of hardware, software, networks, and interoperability. Although this article does not substitute for legal counsel, it provides a resource for clinical bioinformaticians to identify and familiarize themselves with regulations affecting their professional functions within the laboratory.

临床生物信息学家在临床分子诊断实验室中起着至关重要的作用。然而，临床实践和培训这一新兴专业群体所需的核心知识尚未建立。临床实验室受到众多政府和非政府机构的一套复杂的法律和认证要求的约束，这些要求涵盖了以测试结果和中间数据文件的形式产生、处理、存储和分发患者数据。临床生物信息学家密切参与执行这些活动的系统的开发和维护。这是分子病理学协会临床生物信息学家知识体系核心系列的第三份手稿，为临床生物信息学家提供了一个知识体系，描述了硬件、软件、网络和互操作性领域的相关实验室法规和数据安全。虽然这份手稿不能代替法律顾问，但它为临床生物信息学家提供了一个资源，以识别和熟悉影响他们在实验室专业功能的法规。

{"title":"Clinical Bioinformatician Body of Knowledge—Clinical Laboratory Regulation and Data Security Core","authors":"Ryan J. Schmidt , Larissa V. Furtado , Amber M. Fussell , Danielle Jordan , Matthew Lebo , Aijazuddin Syed , Robyn L. Temple-Smolkin , Eric Venner , Elizabeth Worthey , Alexis B. Carter","doi":"10.1016/j.jmoldx.2025.04.003","DOIUrl":"10.1016/j.jmoldx.2025.04.003","url":null,"abstract":"<div><div>Clinical bioinformaticians have come to play an essential role in clinical molecular diagnostic laboratories. However, the core knowledge needed for the clinical practice and training of this emerging group of professionals has not been previously established. Clinical laboratories are subject to a complex set of legal and accreditation requirements from numerous governmental and nongovernmental bodies that cover the generation, processing, storage, and distribution of patient data in the form of test results and intermediate data files. Clinical bioinformaticians are intimately involved in the development and maintenance of systems that perform these activities. This third article in the Association for Molecular Pathology's Clinical Bioinformatician Body of Knowledge Core series presents a body of knowledge for the clinical bioinformatician describing relevant laboratory regulations and data security in the domains of hardware, software, networks, and interoperability. Although this article does not substitute for legal counsel, it provides a resource for clinical bioinformaticians to identify and familiarize themselves with regulations affecting their professional functions within the laboratory.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 7","pages":"Pages 583-601"},"PeriodicalIF":3.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038631","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

A New Era for Molecular Diagnostics 分子诊断的新时代：重拾病人护理的战略眼光。

IF 3.4 3区医学 Q1 PATHOLOGY

Journal of Molecular Diagnostics

Pub Date : 2025-05-02 DOI: 10.1016/j.jmoldx.2025.04.002

Alanna J. Church

引用次数: 0

Clinical Validation of a Noninvasive Multi-Omics Method for Multicancer Early Detection in Retrospective and Prospective Cohorts 一种无创多组学方法在回顾性和前瞻性队列中用于多种癌症早期检测的临床验证。

IF 3.4 3区医学 Q1 PATHOLOGY

Journal of Molecular Diagnostics

Pub Date : 2025-04-29 DOI: 10.1016/j.jmoldx.2025.04.001

Shiyong Li , Shuaipeng Geng , Yan Chen , Qingqi Ren , Yi Luan , Weijie Liang , Yinyin Chang , Lijuan Zhang , Dandan Zhu , Wei Wu , Yingying Zhang , Linfeng Zhang , Yan Wang , Guolin Zhong , Bing Wei , Jie Ma , Yu Chang , Xinhua Wang , Zhiming Li , Chaohui Duan , Mao Mao

Recent studies highlight the promise of blood-based multicancer early detection (MCED) tests for identifying asymptomatic patients with cancer. However, most focus on a single cancer hallmark, thus limiting effectiveness because of cancer's heterogeneity. Here, a blood-based multi-omics test named SeekInCare for MCED is reported. SeekInCare incorporates multiple genomic and epigenetic hallmarks, including copy number aberration, fragment size, end motif, and oncogenic virus, via shallow whole-genome sequencing from cell-free DNA, alongside seven protein tumor markers in one tube of blood. Artificial intelligence algorithms were developed to distinguish patients with cancer from individuals without cancer and to predict the likely affected organ. The retrospective study included 617 patients with cancer and 580 individuals without cancer, covering 27 cancer types. SeekInCare achieved 60.0% sensitivity at 98.3% specificity, resulting in an area under the curve of 0.899. Sensitivities were 37.7%, 50.4%, 66.7%, and 78.1% in patients with stage I, II, III, and IV disease, respectively. Additionally, SeekInCare was evaluated in a prospective cohort consisting of 1203 individuals who received the test as a laboratory-developed test (median follow-up time, 753 days) in which it achieved 70.0% sensitivity at 95.2% specificity. The performances of SeekInCare in both retrospective and prospective studies demonstrate that SeekInCare is a blood-based MCED test, showing comparable performance to the other tests currently in development. These findings support its potential clinical utility as a cancer screening test in high-risk populations.

最近的研究强调了基于血液的多癌早期检测（MCED）检测在识别无症状癌症患者方面的前景。然而，由于癌症的异质性，大多数研究都集中在单一的癌症特征上，从而限制了有效性。本文报道了一种基于血液的多组学检测方法，名为SeekInCare。SeekInCare结合了多种基因组和表观遗传学特征，包括拷贝数畸变、片段大小、末端基序和致癌病毒，通过对无细胞DNA进行浅全基因组测序，以及一管血液中的七种蛋白质肿瘤标记物。开发了人工智能算法来区分癌症患者和非癌症患者，并预测可能受影响的器官。这项回顾性研究包括617名癌症患者和580名非癌症患者，涵盖27种癌症类型。SeekInCare的灵敏度为60.0%，特异度为98.3%，曲线下面积为0.899。I、II、III和IV期患者的敏感性分别为37.7%、50.4%、66.7%和78.1%。此外，SeekInCare在一个前瞻性队列中进行了评估，该队列由1203名个体组成，这些个体接受了作为实验室开发的测试（中位随访时间为753天），其灵敏度为70.0%，特异性为95.2%。SeekInCare在回顾性和前瞻性研究中的表现表明，SeekInCare是一种基于血液的MCED测试，其性能与目前正在开发的其他测试相当。这些发现支持了它作为高风险人群癌症筛查试验的潜在临床应用。

{"title":"Clinical Validation of a Noninvasive Multi-Omics Method for Multicancer Early Detection in Retrospective and Prospective Cohorts","authors":"Shiyong Li , Shuaipeng Geng , Yan Chen , Qingqi Ren , Yi Luan , Weijie Liang , Yinyin Chang , Lijuan Zhang , Dandan Zhu , Wei Wu , Yingying Zhang , Linfeng Zhang , Yan Wang , Guolin Zhong , Bing Wei , Jie Ma , Yu Chang , Xinhua Wang , Zhiming Li , Chaohui Duan , Mao Mao","doi":"10.1016/j.jmoldx.2025.04.001","DOIUrl":"10.1016/j.jmoldx.2025.04.001","url":null,"abstract":"<div><div>Recent studies highlight the promise of blood-based multicancer early detection (MCED) tests for identifying asymptomatic patients with cancer. However, most focus on a single cancer hallmark, thus limiting effectiveness because of cancer's heterogeneity. Here, a blood-based multi-omics test named SeekInCare for MCED is reported. SeekInCare incorporates multiple genomic and epigenetic hallmarks, including copy number aberration, fragment size, end motif, and oncogenic virus, via shallow whole-genome sequencing from cell-free DNA, alongside seven protein tumor markers in one tube of blood. Artificial intelligence algorithms were developed to distinguish patients with cancer from individuals without cancer and to predict the likely affected organ. The retrospective study included 617 patients with cancer and 580 individuals without cancer, covering 27 cancer types. SeekInCare achieved 60.0% sensitivity at 98.3% specificity, resulting in an area under the curve of 0.899. Sensitivities were 37.7%, 50.4%, 66.7%, and 78.1% in patients with stage I, II, III, and IV disease, respectively. Additionally, SeekInCare was evaluated in a prospective cohort consisting of 1203 individuals who received the test as a laboratory-developed test (median follow-up time, 753 days) in which it achieved 70.0% sensitivity at 95.2% specificity. The performances of SeekInCare in both retrospective and prospective studies demonstrate that SeekInCare is a blood-based MCED test, showing comparable performance to the other tests currently in development. These findings support its potential clinical utility as a cancer screening test in high-risk populations.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 7","pages":"Pages 657-670"},"PeriodicalIF":3.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030491","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

Analytical Validation of Next-Generation Sequencing–Based Comprehensive Liquid Biopsy Assay for Therapy Selection 新一代基于测序的综合液体活检检测在治疗选择中的分析验证

IF 3.4 3区医学 Q1 PATHOLOGY

Journal of Molecular Diagnostics

Pub Date : 2025-04-24 DOI: 10.1016/j.jmoldx.2025.02.005

Hala Boulos, Christine Lo, Wei Zhu, Terri M. Driessen, Jason Yamada-Hanff, Taylor Harding, Ariane Lozac'hmeur, Tiana Pereira, Anne Sonnenschein, Josh Och, Ailin Jin, Nirali Patel, Rick Blidner, Robert Tell, Jonathan Freaney, Nike Beaubier, Brett Mahon

Liquid biopsies are an increasingly important tool for the real-time monitoring of biomarkers, cancer recurrence, and disease burden in oncology practice. Tempus xF+ is a liquid biopsy assay that detects cell-free DNA in blood samples of patients with advanced solid tumors. The xF+ panel covers 523 genes spanning approximately 1.8 Mb of the human genome and can detect single-nucleotide variants and insertions-deletions in 522 genes. It also detects copy number gains in 7 genes and translocations (gene rearrangements) in 10 genes. Furthermore, the larger panel size allows for the calculation of blood tumor mutational burden. This work highlights the analytical validation performed for the xF+ assay, comparing it with a smaller panel liquid biopsy assay, calculating blood tumor mutational burden, and exploring its potential clinical utility.

在肿瘤实践中，液体活检是实时监测生物标志物、癌症复发和疾病负担的越来越重要的工具。Tempus xF+是一种液体活检技术，用于检测晚期实体瘤患者血液样本中的无细胞DNA。xF+面板涵盖了523个基因，跨越大约1.8 Mb的人类基因组，可以检测522个基因的单核苷酸变异和插入-缺失。它还检测到7个基因的拷贝数增加和10个基因的易位（基因重排）。此外，更大的面板尺寸允许计算血液肿瘤突变负担。这项工作强调了对xF+测定法进行的分析验证，将其与较小的面板液体活检法进行比较，计算血液肿瘤突变负担，并探索其潜在的临床应用。

{"title":"Analytical Validation of Next-Generation Sequencing–Based Comprehensive Liquid Biopsy Assay for Therapy Selection","authors":"Hala Boulos, Christine Lo, Wei Zhu, Terri M. Driessen, Jason Yamada-Hanff, Taylor Harding, Ariane Lozac'hmeur, Tiana Pereira, Anne Sonnenschein, Josh Och, Ailin Jin, Nirali Patel, Rick Blidner, Robert Tell, Jonathan Freaney, Nike Beaubier, Brett Mahon","doi":"10.1016/j.jmoldx.2025.02.005","DOIUrl":"10.1016/j.jmoldx.2025.02.005","url":null,"abstract":"<div><div>Liquid biopsies are an increasingly important tool for the real-time monitoring of biomarkers, cancer recurrence, and disease burden in oncology practice. Tempus xF+ is a liquid biopsy assay that detects cell-free DNA in blood samples of patients with advanced solid tumors. The xF+ panel covers 523 genes spanning approximately 1.8 Mb of the human genome and can detect single-nucleotide variants and insertions-deletions in 522 genes. It also detects copy number gains in 7 genes and translocations (gene rearrangements) in 10 genes. Furthermore, the larger panel size allows for the calculation of blood tumor mutational burden. This work highlights the analytical validation performed for the xF+ assay, comparing it with a smaller panel liquid biopsy assay, calculating blood tumor mutational burden, and exploring its potential clinical utility.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 5","pages":"Pages 383-394"},"PeriodicalIF":3.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864750","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 the Clinical Performance and Reproducibility of the Savanna HSV 1+2/VZV Assay 热带草原HSV 1+2/VZV检测的临床性能和可重复性验证。

IF 3.4 3区医学 Q1 PATHOLOGY

Journal of Molecular Diagnostics

Pub Date : 2025-04-23 DOI: 10.1016/j.jmoldx.2025.03.009

Matthew L. Faron , Jane M. Caldwell , Lavannya Sabharwal , Amorina Purpora , Jennifer Meece , Puspa Bhattarai , Julie O’Neill , Melody Christian , Neelam X. Dhiman , Jennifer Halliday , Jessica S. Hoff , Carrie V. Vause , Paul A. Granato

Herpes simplex virus 1 (HSV-1), HSV 2 (HSV-2), and varicella-zoster virus (VZV) cause nondescript cutaneous and mucocutaneous lesions requiring rapid, differential identification for appropriate diagnosis and patient counseling. Decentralized multiplex molecular assays may provide more rapid results than existing methodologies but require clinical validation. This multicenter study evaluated the clinical performance of the Savanna HSV 1+2/VZV Assay against the high-complexity Lyra Direct HSV 1+2/VZV real-time PCR nucleic acid test for the detection of HSV-1, HSV-2, and VZV from clinical specimens. The Savanna HSV 1+2/VZV Assay is an automated, moderate-complexity, real-time PCR assay recently cleared by the US Food and Drug Administration for the simultaneous detection and differentiation of HSV-1, HSV-2, and VZV DNA isolated from lesion swabs. In this study, 744 clinical specimens (531 female, 213 male) were evaluated by Savanna and compared with Lyra. Discrepant result analysis was conducted with the moderate-complexity Solana HSV 1+2/VZV isothermal nucleic acid test. For 744 clinical samples, Savanna exhibited overall, positive, and negative percent agreement of 99.5%, 100%, and 99.3% for HSV-1; 99.9%, 100%, and 99.8% for HSV-2; and 100%, 100%, and 100% for VZV. The Savanna HSV 1+2/VZV Assay exhibited excellent performance in a multicenter, clinical study. Savanna can provide laboratory-equivalent results outside of the central laboratory with the potential to deliver accurate results during the patient visit.

单纯疱疹病毒1型（HSV-1）、单纯疱疹病毒2型（HSV-2）和水痘-带状疱疹病毒（VZV）感染引起难以描述的皮肤和粘膜病变，需要快速鉴别识别，以确保适当的诊断和患者咨询。可在中心实验室之外使用的对这些病原体的多重分子分析可能比现有方法提供更快的结果，但它们需要临床验证。本多中心研究比较了Savanna HSV 1+2/VZV检测与Lyra Direct HSV 1+2/VZV实时PCR核酸检测（NAAT）在临床标本中检测HSV-1、HSV-2和VZV的临床表现。Savanna HSV 1+2/VZV检测是一种自动化的、中等复杂程度的实时PCR检测方法，最近被美国食品和药物管理局批准，用于同时检测和分化从病变拭子中分离的HSV-1、HSV-2和VZV DNA。本研究共收集744例临床标本，其中女性531例，男性213例，并与Lyra进行比较。采用美国食品药品监督管理局批准的中等复杂度Solana HSV 1+2/VZV等温核酸检测进行差异结果分析。在744份临床样本中，Savanna对HSV-1的总体、阳性和阴性百分比的一致性分别为99.5%、100%和99.3%；2型单纯疱疹病毒感染率分别为99.9%、100%和99.8%；VZV是100%，100%,100%Savanna HSV 1+2/VZV检测在多中心临床研究中表现优异。Savanna可以在中心实验室之外提供与实验室相当的结果，并有可能在患者就诊期间提供准确的结果。

{"title":"Validation of the Clinical Performance and Reproducibility of the Savanna HSV 1+2/VZV Assay","authors":"Matthew L. Faron , Jane M. Caldwell , Lavannya Sabharwal , Amorina Purpora , Jennifer Meece , Puspa Bhattarai , Julie O’Neill , Melody Christian , Neelam X. Dhiman , Jennifer Halliday , Jessica S. Hoff , Carrie V. Vause , Paul A. Granato","doi":"10.1016/j.jmoldx.2025.03.009","DOIUrl":"10.1016/j.jmoldx.2025.03.009","url":null,"abstract":"<div><div>Herpes simplex virus 1 (HSV-1), HSV 2 (HSV-2), and varicella-zoster virus (VZV) cause nondescript cutaneous and mucocutaneous lesions requiring rapid, differential identification for appropriate diagnosis and patient counseling. Decentralized multiplex molecular assays may provide more rapid results than existing methodologies but require clinical validation. This multicenter study evaluated the clinical performance of the Savanna HSV 1+2/VZV Assay against the high-complexity Lyra Direct HSV 1+2/VZV real-time PCR nucleic acid test for the detection of HSV-1, HSV-2, and VZV from clinical specimens. The Savanna HSV 1+2/VZV Assay is an automated, moderate-complexity, real-time PCR assay recently cleared by the US Food and Drug Administration for the simultaneous detection and differentiation of HSV-1, HSV-2, and VZV DNA isolated from lesion swabs. In this study, 744 clinical specimens (531 female, 213 male) were evaluated by Savanna and compared with Lyra. Discrepant result analysis was conducted with the moderate-complexity Solana HSV 1+2/VZV isothermal nucleic acid test. For 744 clinical samples, Savanna exhibited overall, positive, and negative percent agreement of 99.5%, 100%, and 99.3% for HSV-1; 99.9%, 100%, and 99.8% for HSV-2; and 100%, 100%, and 100% for VZV. The Savanna HSV 1+2/VZV Assay exhibited excellent performance in a multicenter, clinical study. Savanna can provide laboratory-equivalent results outside of the central laboratory with the potential to deliver accurate results during the patient visit.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 7","pages":"Pages 605-614"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038495","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

Analytical Validation and Clinical Sensitivity of the Belay Summit Assay for the Detection of DNA Variants in Cerebrospinal Fluid of Primary and Metastatic Central Nervous System Cancer 原发性和转移性中枢神经系统癌脑脊液DNA变异检测的分析验证和临床敏感性

IF 3.4 3区医学 Q1 PATHOLOGY

Journal of Molecular Diagnostics

Pub Date : 2025-04-23 DOI: 10.1016/j.jmoldx.2025.03.010

Qian Nie, Kala F. Schilter, Kyle M. Hernandez, Jennifer N. Adams, Rakshitha Jagadish, Anthony Acevedo, Alexandra Larson, Brett A. Domagala, Samantha A. Vo, Sakshi Khurana, Kathleen Mitchell, Dean Ellis, Baymuhammet Muhammedov, Yuxuan Wang, Christopher Douville, Brian Coe, Chetan Bettegowda, Honey V. Reddi

In contrast to most solid tumors, cancers of the central nervous system (CNS) pose a unique challenge for effective detection and tracking via plasma because of the blood-brain barrier. Informed diagnosis of primary and metastatic CNS tumors can be facilitated using a liquid biopsy assay that evaluates tumor-derived DNA from the cerebrospinal fluid (CSF), potentially increasing the efficacy of diagnosis and reducing the uncertainty and morbidities associated with the current standard of care that involves neurosurgical procedures. The Belay Summit assay involves tumor-derived DNA–based genomic profiling of CSF to inform diagnosis of CNS tumors. The analytical sensitivity of Summit for single-nucleotide/multinucleotide variants and insertions/deletions is 96% at a 95% limit of detection of 0.30% variant allele fraction. Analytical sensitivity for chromosomal arm-level aneuploidy is 91% at abs(log2r) of 0.09 limit of detection. Clinical sensitivity across a cohort of 124 specimens, including primary and metastatic CNS tumors, was demonstrated to be 90% with a specificity of 95%, supporting the potential for positive clinical utility. These results demonstrate that the Belay Summit assay can accurately and reproducibly be used to inform the diagnosis of primary and metastatic CNS tumors using CSF.

与大多数实体瘤不同，由于血脑屏障的存在，中枢神经系统（CNS）的癌症对通过血浆进行有效检测和跟踪提出了独特的挑战。使用液体活检法评估脑脊液（CSF）中肿瘤来源的DNA，可以促进原发性和转移性中枢神经系统肿瘤的知情诊断，潜在地提高诊断的有效性，并减少与目前涉及神经外科手术的护理标准相关的不确定性和发病率。Belay Summit检测包括肿瘤来源的基于dna的脑脊液基因组分析，以告知中枢神经系统肿瘤的诊断。在0.30%变异等位基因分数的95%检测限下，Summit对单核苷酸/多核苷酸变异和插入/缺失的分析灵敏度为96%。染色体臂水平非整倍体在abs(log2r) 0.09检测限时的分析灵敏度为91%。124个标本的临床敏感性，包括原发性和转移性中枢神经系统肿瘤，被证明为90%，特异性为95%，支持潜在的积极临床应用。这些结果表明，Belay Summit试验可以准确且可重复地用于脑脊液对原发性和转移性中枢神经系统肿瘤的诊断。

{"title":"Analytical Validation and Clinical Sensitivity of the Belay Summit Assay for the Detection of DNA Variants in Cerebrospinal Fluid of Primary and Metastatic Central Nervous System Cancer","authors":"Qian Nie, Kala F. Schilter, Kyle M. Hernandez, Jennifer N. Adams, Rakshitha Jagadish, Anthony Acevedo, Alexandra Larson, Brett A. Domagala, Samantha A. Vo, Sakshi Khurana, Kathleen Mitchell, Dean Ellis, Baymuhammet Muhammedov, Yuxuan Wang, Christopher Douville, Brian Coe, Chetan Bettegowda, Honey V. Reddi","doi":"10.1016/j.jmoldx.2025.03.010","DOIUrl":"10.1016/j.jmoldx.2025.03.010","url":null,"abstract":"<div><div>In contrast to most solid tumors, cancers of the central nervous system (CNS) pose a unique challenge for effective detection and tracking via plasma because of the blood-brain barrier. Informed diagnosis of primary and metastatic CNS tumors can be facilitated using a liquid biopsy assay that evaluates tumor-derived DNA from the cerebrospinal fluid (CSF), potentially increasing the efficacy of diagnosis and reducing the uncertainty and morbidities associated with the current standard of care that involves neurosurgical procedures. The Belay Summit assay involves tumor-derived DNA–based genomic profiling of CSF to inform diagnosis of CNS tumors. The analytical sensitivity of Summit for single-nucleotide/multinucleotide variants and insertions/deletions is 96% at a 95% limit of detection of 0.30% variant allele fraction. Analytical sensitivity for chromosomal arm-level aneuploidy is 91% at abs(log2r) of 0.09 limit of detection. Clinical sensitivity across a cohort of 124 specimens, including primary and metastatic CNS tumors, was demonstrated to be 90% with a specificity of 95%, supporting the potential for positive clinical utility. These results demonstrate that the Belay Summit assay can accurately and reproducibly be used to inform the diagnosis of primary and metastatic CNS tumors using CSF.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 7","pages":"Pages 615-629"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042528","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

Fragile X Syndrome Carrier Screening Using a Nanopore Sequencing Assay 使用纳米孔测序法筛选脆性X综合征携带者。

IF 3.4 3区医学 Q1 PATHOLOGY

Journal of Molecular Diagnostics

Pub Date : 2025-04-23 DOI: 10.1016/j.jmoldx.2025.03.008

Zhongmin Xia , Qiuxiao Deng , Ping Hu , Chunliu Gao , Yu Jiang , Yulin Zhou , Qiwei Guo

Fragile X syndrome (FXS) is the leading cause of monogenic autism spectrum disorder and inherited intellectual disabilities. Although the value of population-based FXS carrier screening has been acknowledged, appropriate screening methods are urgently required to establish and implement screening programs. We developed a nanopore sequencing–based assay that includes data analysis software to identify FXS carriers. Reference and clinical samples were used to evaluate the performance of the nanopore sequencing assay. Triplet-primed PCR and PacBio sequencing assays were used for comparisons. Nanopore sequencing identified reference carrier samples with a full range of premutation alleles in single-, 10-, and 100-plex assays, and identified AGG interruptions in an allele-specific manner. Moreover, nanopore sequencing revealed no size preference for amplicons containing different-length CGG repeat regions. Finally, nanopore sequencing successfully identified three carriers among 10 clinical samples for preliminary clinical validation. The observed variation in CGG repeat region size resulted from the base calling process of nanopore sequencing. In conclusion, the nanopore sequencing assay is rapid, high-capacity, inexpensive, and easy to perform, thus providing a promising tool and paving the way for population-based FXS carrier screening.

脆性X染色体综合征（FXS）是单基因自闭症谱系障碍和遗传性智力残疾的主要原因。虽然基于人群的FXS携带者筛查的价值已得到认可，但迫切需要适当的筛查方法来建立和实施筛查计划。我们开发了一种基于纳米孔测序的检测方法，其中包括数据分析软件来识别FXS携带者。采用参考样本和临床样本评估纳米孔测序法的性能。采用三重引物PCR和PacBio测序法进行比较。纳米孔测序在单、10和100 plex分析中鉴定了具有全范围预突变等位基因的参考载体样本，并以等位基因特异性的方式鉴定了AGG中断。此外，纳米孔测序显示，含有不同长度CGG重复区域的扩增子没有尺寸偏好。最后，纳米孔测序成功地从10个临床样本中鉴定出3个携带者，进行初步临床验证。观察到的CGG重复区大小的变化是由纳米孔测序的碱基调用过程引起的。总之，纳米孔测序分析具有快速、高容量、廉价和易于执行的特点，因此为基于人群的FXS载体筛选提供了一种有前途的工具。

{"title":"Fragile X Syndrome Carrier Screening Using a Nanopore Sequencing Assay","authors":"Zhongmin Xia , Qiuxiao Deng , Ping Hu , Chunliu Gao , Yu Jiang , Yulin Zhou , Qiwei Guo","doi":"10.1016/j.jmoldx.2025.03.008","DOIUrl":"10.1016/j.jmoldx.2025.03.008","url":null,"abstract":"<div><div>Fragile X syndrome (FXS) is the leading cause of monogenic autism spectrum disorder and inherited intellectual disabilities. Although the value of population-based FXS carrier screening has been acknowledged, appropriate screening methods are urgently required to establish and implement screening programs. We developed a nanopore sequencing–based assay that includes data analysis software to identify FXS carriers. Reference and clinical samples were used to evaluate the performance of the nanopore sequencing assay. Triplet-primed PCR and PacBio sequencing assays were used for comparisons. Nanopore sequencing identified reference carrier samples with a full range of premutation alleles in single-, 10-, and 100-plex assays, and identified AGG interruptions in an allele-specific manner. Moreover, nanopore sequencing revealed no size preference for amplicons containing different-length CGG repeat regions. Finally, nanopore sequencing successfully identified three carriers among 10 clinical samples for preliminary clinical validation. The observed variation in CGG repeat region size resulted from the base calling process of nanopore sequencing. In conclusion, the nanopore sequencing assay is rapid, high-capacity, inexpensive, and easy to perform, thus providing a promising tool and paving the way for population-based FXS carrier screening.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 7","pages":"Pages 645-656"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003650","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

Catching Up to Increased Complexity in Breast Cancer Molecular Testing 乳腺癌分子检测日益复杂。

IF 3.4 3区医学 Q1 PATHOLOGY

Journal of Molecular Diagnostics

Pub Date : 2025-04-23 DOI: 10.1016/j.jmoldx.2025.03.007

Gregory R. Bean , Chieh-Yu Lin , Melissa Krystel-Whittemore , Lulu Sun

引用次数: 0

Clinical Bioinformatician Body of Knowledge—Molecular Diagnostics Core 临床生物信息学家知识体系-分子诊断核心：分子病理学协会报告。

IF 3.4 3区医学 Q1 PATHOLOGY

Journal of Molecular Diagnostics

Pub Date : 2025-04-23 DOI: 10.1016/j.jmoldx.2025.03.006

Annette Leon , Eduardo Castro-Echeverry , Amber M. Fussell , Danielle Jordan , Nefize S. Kip , Angshumoy Roy , Carlos J. Suarez , Robyn L. Temple-Smolkin , Joshua Coleman

Clinical bioinformaticians play a critical role in clinical molecular diagnostics laboratories as developers of data analysis pipelines, tools, and databases. They also contribute to a variety of other tasks, such as genomic data interpretation, database administration, hardware engineering, informatics, information technology, infrastructure support, and software engineering. To effectively perform these functions, the clinical bioinformaticians must possess a strong foundational knowledge of molecular biology, genetics, genomics, computational biology, and the relevant federal, state, and/or regional regulations, laboratory accreditation requirements, and other standards and best practices. This first article in the Association for Molecular Pathology's Clinical Bioinformatician Body of Knowledge series provides a comprehensive core knowledge base on molecular biology, genetics, genomics, clinical laboratory practices, sequencing technologies, databases, and clinical applications. This resource serves not only to equip clinical bioinformaticians for their professional roles but also as a valuable reference for laboratorians.

临床生物信息学家作为数据分析管道、工具和数据库的开发人员，在临床分子诊断实验室中发挥着关键作用。他们还为各种其他任务做出贡献，例如基因组数据解释、数据库管理、硬件工程、信息学、信息技术、基础设施支持和软件工程。为了有效地履行这些职能，临床生物信息学家必须具备分子生物学、遗传学、基因组学、计算生物学的强大基础知识，以及相关的联邦、州和/或地区法规、实验室认证要求和其他标准和最佳实践。这是分子病理学协会临床生物信息学家知识体系系列的第一篇文章，提供了关于分子生物学、遗传学、基因组学、临床实验室实践、测序技术、数据库和临床应用的全面核心知识库。该资源不仅为临床生物信息学家的专业角色提供了装备，而且为实验室人员提供了有价值的参考。

{"title":"Clinical Bioinformatician Body of Knowledge—Molecular Diagnostics Core","authors":"Annette Leon , Eduardo Castro-Echeverry , Amber M. Fussell , Danielle Jordan , Nefize S. Kip , Angshumoy Roy , Carlos J. Suarez , Robyn L. Temple-Smolkin , Joshua Coleman","doi":"10.1016/j.jmoldx.2025.03.006","DOIUrl":"10.1016/j.jmoldx.2025.03.006","url":null,"abstract":"<div><div>Clinical bioinformaticians play a critical role in clinical molecular diagnostics laboratories as developers of data analysis pipelines, tools, and databases. They also contribute to a variety of other tasks, such as genomic data interpretation, database administration, hardware engineering, informatics, information technology, infrastructure support, and software engineering. To effectively perform these functions, the clinical bioinformaticians must possess a strong foundational knowledge of molecular biology, genetics, genomics, computational biology, and the relevant federal, state, and/or regional regulations, laboratory accreditation requirements, and other standards and best practices. This first article in the Association for Molecular Pathology's Clinical Bioinformatician Body of Knowledge series provides a comprehensive core knowledge base on molecular biology, genetics, genomics, clinical laboratory practices, sequencing technologies, databases, and clinical applications. This resource serves not only to equip clinical bioinformaticians for their professional roles but also as a valuable reference for laboratorians.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 7","pages":"Pages 546-565"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036942","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