Journal of Molecular Diagnostics最新文献

{"title":"Clinical Bioinformatician Body of Knowledge-Bioinformatics and Software Core: A Report of the Association for Molecular Pathology.","authors":"Sabah Kadri, Kelly E Craven, Amber M Fussell, Elaine P S Gee, Danielle Jordan, Eric W Klee, Niklas Krumm, Robyn L Temple-Smolkin, Ahmet Zehir, Weiwei Zhang, Andrea Sboner","doi":"10.1016/j.jmoldx.2025.04.008","DOIUrl":"10.1016/j.jmoldx.2025.04.008","url":null,"abstract":"<p><p>With the evolution of next-generation sequencing-based testing in molecular diagnostics laboratories, the clinical role of bioinformaticians has also evolved. The Association for Molecular Pathology's Clinical Bioinformatician Body of Knowledge aims to define the various roles the clinical bioinformatician operates individually or within a clinical bioinformatics team, along with proficiencies and skill sets that may be required or desirable across these roles. One of the most common professional responsibilities of a clinical bioinformatician is to implement bioinformatics pipelines, either vendor supplied or custom built for the assays in the molecular diagnostics laboratory, along with analysis and quality control of clinical genomics data. This second article in the series describes the various stages in the life cycle of a clinical bioinformatics pipeline and the considerations, areas of expertise, and skill sets required in each stage. This information may help laboratory professionals to better work with clinical bioinformaticians and laboratory directors to hire the appropriate expertise based on the specific needs of the laboratory.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121464","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}

{"title":"Standardizing Laboratory Practices in Pharmacogenomics (STRIPE) consensus conference: Report from the Laboratory Challenges Working Group.","authors":"Victoria M Pratt, Betsy Bove, Raymond A Lorenz, Annette K Taylor, Bronwyn Ramey","doi":"10.1016/j.jmoldx.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2025.04.006","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103001","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}

{"title":"Path to Health Equity and Improved Outcomes through Inclusive Sex and Gender Data Collection in Genomic Testing.","authors":"Marco L Leung, Ina Amarillo, Danielle Jordan, Matthew S Lebo, Rizwan C Naeem, David I Suster, Robyn Temple-Smolkin, Cigdem H Ussakli, Honey V Reddi","doi":"10.1016/j.jmoldx.2025.04.004","DOIUrl":"10.1016/j.jmoldx.2025.04.004","url":null,"abstract":"<p><p>As the demand for health services among sexual and gender diverse (SGD) individuals rises, there is a growing need for comprehensive and equitable standards of care across the health care system. Despite progress in various research areas, there is a relative lag in genetics and genomics. In this Perspective, the Association for Molecular Pathology Working Group presents survey data on how the sex and gender identity of patients, including SGD individuals, is collected, interpreted, and reported within current genomic laboratory practices during the preanalytical, analytical, and postanalytical phases. Recommendations and guidelines related to the care of the SGD community are explored, identifying knowledge and practice gaps in each phase. On the basis of the survey results, review of existing available literature, and collective professional experience, the Working Group provides future considerations to enhance affirmative and inclusive processes, improve test quality, advance health equity, and enhance patient outcomes.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095509","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}

{"title":"Smart Nonuniformity: Calibration of Sequencing Depth of a Targeted Gene Panel to Simultaneously Detect Somatic and Germline Variants.","authors":"Robert L O'Reilly, Philip Harraka, Jared Burke, Daniele Belluoccio, Paul Yeh, Kerryn Howlett, Kiarash Behrouzfar, Amanda Rewse, Helen Tsimiklis, Graham G Giles, John L Hopper, Kristen J Bubb, Stephen J Nicholls, Roger L Milne, Melissa C Southey","doi":"10.1016/j.jmoldx.2025.04.007","DOIUrl":"10.1016/j.jmoldx.2025.04.007","url":null,"abstract":"<p><p>Targeted gene panel sequencing that measures genomic variation at different depths has potential diagnostic application. A targeted gene panel was developed to detect somatic variants associated with clonal hematopoiesis of indeterminate potential (CHIP), which requires an optimal sequencing depth of >500×; and germline variants requiring a lower ≥50× depth (panel 1). This was achieved by adjusting probe ratios for genomic regions relevant to identifying CHIP in comparison to those relevant to germline variation analysis. An additional custom panel containing only the genomic regions relevant to the identification of CHIP (panel 2) was also manufactured to confirm that panel 1 did not miss variants because of the complex design. Both panels were used to sequence 150 blood-derived DNAs; 94 DNAs from research participants aged 64 to 75 years; 16 DNAs with known germline variants; 16 DNAs with known germline variants (titrated from 0% to 100%); 24 DNAs from individuals aged <40 years; and 3 commercial CHIP controls and 3 high-molecular-weight DNA controls. The sequencing median depth ratio between the CHIP and germline relevant genomic regions was 4.7:1. Fourteen CHIP-associated variants were called in both panel 1 (1382× median variant depth) and panel 2 (1665× median variant depth). All known germline variants were identified (251× median variant depth). Smart nonuniformity sequencing reliably detects variants with allele frequency in the range >0.01 to 1 in one workflow.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095511","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}

{"title":"Leveraging RNA from DNA Extraction Lysate to Rescue \"Insufficient\" Samples for More Comprehensive Genomic Profiling in Patients with Scant Tumor Specimens.","authors":"Mark D Ewalt, Sara E DiNapoli, Kerry Mullaney, Alison Urvalek, Minji Kim Uh, Purvil Sukhadia, J Keith Killian, Michael Zaidinski, Hun Jae Jung, Tiffany McFarlane, Kelly Rios-Papachristos, Alexander Drilon, Mark G Kris, Khedoudja Nafa, Maria E Arcila, Marc Ladanyi, Ahmet Zehir, Michael Offin, Ryma Benayed","doi":"10.1016/j.jmoldx.2025.04.005","DOIUrl":"10.1016/j.jmoldx.2025.04.005","url":null,"abstract":"<p><p>Tissue availability is often a limiting factor in obtaining comprehensive genomic profiling to identify actionable oncogenic drivers in tumors from patients with cancer. The utility of performing complementary DNA and RNA sequencing to better identify targetable gene fusions was previously reported. Here, we report our experience using RNA recovered from lysate material, following DNA extraction, to perform targeted RNA sequencing and identify gene fusions and oncogenic transcript variants in a large cohort of patients with solid tumors. To validate this approach, RNA-sequencing results of lysate-extracted RNA and direct formalin-fixed, paraffin-embedded (FFPE) extracted RNA from the same tumors were compared. After finding equivalent identification of oncogenic gene fusions and transcript variants, efforts were expanded to a larger cohort across more diverse tumor types. Lysate-extracted RNA performed comparably to freshly FFPE extract RNA, with 97% and 96% success rates, respectively. Within the lysate-extracted group, it was documented that lysate was the only material available for RNA extraction (n = 1862, 42% of all tested samples) and, within this subgroup, 364 (20%) samples were positive for actionable fusions or oncogenic isoforms. Using RNA recovered from lysate can permit sequential or simultaneous comprehensive DNA/RNA sequencing from scant FFPE samples in laboratories where dual sample extraction is not logistically possible, allowing more complete profiling to enhance the identification of actionable oncogenic gene fusions to guide care.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095416","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}

{"title":"Analytical Performance of the NCI-myeloMATCH Assay: A Rapid Turnaround Genomic Profiling Assay for Myeloid Disorders.","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":"<p><p>myeloMATCH is a National Cancer Institute precision medicine clinical trial initiative to evaluate treatments for acute myeloid leukemia and myelodysplastic syndrome based on a patient's diagnostic presenting clinical and genetic profile. The National Cancer Institute myeloid assay version 2 (NMAv2) uses the Ion Torrent Genexus System, an automated platform with <48-hour turnaround from specimen receipt to reporting, to provide regulatory-compliant use for myeloMATCH across two independent clinical laboratories with harmonized workflows. Using marrow aspirate or peripheral blood 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 it can rapidly characterize genomic alterations in acute myeloid leukemia and myelodysplastic syndrome.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"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}

{"title":"Clinical Bioinformatician Body of Knowledge-Clinical Laboratory Regulation and Data Security Core: A Report of the Association for Molecular Pathology.","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":"<p><p>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.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"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}

{"title":"A New Era for Molecular Diagnostics: Reclaiming Strategic Vision for Patient Care.","authors":"Alanna J Church","doi":"10.1016/j.jmoldx.2025.04.002","DOIUrl":"10.1016/j.jmoldx.2025.04.002","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056654","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}

{"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, Guanghui Long, Mao Mao","doi":"10.1016/j.jmoldx.2025.04.001","DOIUrl":"10.1016/j.jmoldx.2025.04.001","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"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}

{"title":"Analytical Validation of Next-Generation Sequencing–Based Comprehensive Liquid Biopsy Assay for Therapy Selection","authors":"Hala Boulos,&nbsp;Christine Lo,&nbsp;Wei Zhu,&nbsp;Terri M. Driessen,&nbsp;Jason Yamada-Hanff,&nbsp;Taylor Harding,&nbsp;Ariane Lozac'hmeur,&nbsp;Tiana Pereira,&nbsp;Anne Sonnenschein,&nbsp;Josh Och,&nbsp;Ailin Jin,&nbsp;Nirali Patel,&nbsp;Rick Blidner,&nbsp;Robert Tell,&nbsp;Jonathan Freaney,&nbsp;Nike Beaubier,&nbsp;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}