Journal of Molecular Diagnostics最新文献_第2页

Equivalent Clinical Accuracy of Human Papillomavirus DNA Testing Using Cobas 4800 and 6800 Human Papillomavirus Systems in Paired Urine and Cervical Samples.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-03-18 DOI: 10.1016/j.jmoldx.2025.02.004

Severien Van Keer, Ardashel Latsuzbaia, Davy Vanden Broeck, Philippe De Sutter, Gilbert Donders, Jean Doyen, Wiebren A A Tjalma, Steven Weyers, Marc Arbyn, Alex Vorsters

{"title":"Equivalent Clinical Accuracy of Human Papillomavirus DNA Testing Using Cobas 4800 and 6800 Human Papillomavirus Systems in Paired Urine and Cervical Samples.","authors":"Severien Van Keer, Ardashel Latsuzbaia, Davy Vanden Broeck, Philippe De Sutter, Gilbert Donders, Jean Doyen, Wiebren A A Tjalma, Steven Weyers, Marc Arbyn, Alex Vorsters","doi":"10.1016/j.jmoldx.2025.02.004","DOIUrl":"10.1016/j.jmoldx.2025.02.004","url":null,"abstract":"The use of urine for cervical cancer screening is gaining international attention, although more data on the relative clinical accuracy of validated human papillomavirus (HPV) DNA tests on urine versus cervical samples are needed. This study primarily seeks to evaluate the clinical performance of Roche cobas 4800 and 6800 HPV Systems in first-void urine, collected at home, compared with clinician-collected cervical samples. Paired first-void urine (index test) and cervical samples (comparator test) from 499 females enrolled at five Belgian colposcopy clinics were analyzed with cobas HPV Systems. Colposcopy and histology of biopsies were used as reference test (trial registration number: NCT03064087). Sample processing protocols and clinical thresholds proposed by the manufacturer for cervical samples were also applied for first-void urine. In the total study population, HPV testing on first-void urine was similarly sensitive [ratiocervical intraepithelial neoplasia 2+ (CIN2+), 0.98; 95% CI, 0.93-1.02] and specific for cobas 4800 HPV (ratio< CIN2, 1.00; 95% CI, 0.91-1.10) and cobas HPV for use on the cobas 6800 System (ratioCIN2+, 0.96; 95% CI, 0.91-1.02; ratio< CIN2, 1.01; 95% CI, 0.93-1.09) compared with cervical samples (P ≥ 0.05). Good to excellent HPV test agreements between paired samples were observed (κ = 0.68 to 0.87). In summary, HPV testing using cobas 4800 and 6800 HPV Systems was as accurate on first-void urine as on cervical samples collected by a clinician.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671419","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

Rapid, Reliable, and Interpretable Copy Number Variant Curation Visualizations for Diagnostic Settings with SeeNV.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-03-03 DOI: 10.1016/j.jmoldx.2025.01.008

Michael S Bradshaw, Jishnu Raychaudhuri, Lachlan Murphy, Rebecca Barnard, Taylor Firman, Alisa A Gaskell, Ryan M Layer

{"title":"Rapid, Reliable, and Interpretable Copy Number Variant Curation Visualizations for Diagnostic Settings with SeeNV.","authors":"Michael S Bradshaw, Jishnu Raychaudhuri, Lachlan Murphy, Rebecca Barnard, Taylor Firman, Alisa A Gaskell, Ryan M Layer","doi":"10.1016/j.jmoldx.2025.01.008","DOIUrl":"10.1016/j.jmoldx.2025.01.008","url":null,"abstract":"Copy number variants (CNVs), structural alterations in the genome involving duplication or deletion of DNA segments, are implicated in various health conditions. Despite their clinical significance, accurate identification and interpretation of CNVs remain challenging, especially in the context of whole-exome sequencing (WES), which is commonly used in clinical diagnostic laboratories. Although WES offers economic advantages over whole-genome sequencing, it struggles with CNV detection because of technical noise introduced by laboratory and analytic processes. Manual curation of CNV calls generated by these tools is labor intensive and error prone. To address this, SeeNV, a command-line tool, is introduced to aid manual curation of CNVs at scale. SeeNV is one solution to these issues, developed in collaboration with and used by the Precision Diagnostics Laboratory at Children's Hospital Colorado. SeeNV generates static infographics for each CNV, incorporating sample and cohort sequencing coverage statistics, CNV population frequency, and, more, facilitating rapid and precise assessment. Using CNV calls identified in publicly available WES and whole-genome sequencing samples, users can rapidly and reliably curate CNV calls, needing only 4.3 seconds to curate a call, achieving 0.95 recall (analytical sensitivity) and 0.74 precision (positive predictive value). SeeNV is freely available for download on GitHub.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568766","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

Detection of Gene Fusions and Rearrangements in Formalin-Fixed, Paraffin-Embedded Solid Tumor Specimens Using High-Throughput Chromosome Conformation Capture. 使用 Hi-C 检测 FFPE 实体瘤标本中的基因融合和重排。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-27 DOI: 10.1016/j.jmoldx.2025.01.007

Kristyn Galbraith, Jamin Wu, Kristin Sikkink, Hussein Mohamed, Derek Reid, Michelle Perez-Arreola, Jon-Matthew Belton, Sofia Nomikou, Shadi Melnyk, Yiying Yang, Benjamin L Liechty, George Jour, Aristotelis Tsirigos, David J Hermel, Alyssa Beck, Darren Sigal, Nathan A Dahl, Rajeev Vibhakar, Anthony Schmitt, Matija Snuderl

{"title":"Detection of Gene Fusions and Rearrangements in Formalin-Fixed, Paraffin-Embedded Solid Tumor Specimens Using High-Throughput Chromosome Conformation Capture.","authors":"Kristyn Galbraith, Jamin Wu, Kristin Sikkink, Hussein Mohamed, Derek Reid, Michelle Perez-Arreola, Jon-Matthew Belton, Sofia Nomikou, Shadi Melnyk, Yiying Yang, Benjamin L Liechty, George Jour, Aristotelis Tsirigos, David J Hermel, Alyssa Beck, Darren Sigal, Nathan A Dahl, Rajeev Vibhakar, Anthony Schmitt, Matija Snuderl","doi":"10.1016/j.jmoldx.2025.01.007","DOIUrl":"10.1016/j.jmoldx.2025.01.007","url":null,"abstract":"Chromosomal structural variants (SVs) are major contributors to cancer development. Although multiple methods exist for detecting SVs, they are limited in throughput, such as fluorescent in situ hybridization and targeted panels, and use RNA, which degrades in formalin-fixed, paraffin-embedded (FFPE) blocks and is unable to detect SVs that do not produce a fusion transcript. High-throughput chromosome conformation capture (Hi-C) is a DNA-based next-generation sequencing (NGS) method that preserves the spatial conformation of the genome, capturing long-range genetic interactions and SVs. Herein, a retrospective study analyzing 71 FFPE specimens from 10 different solid tumors was performed. Results showed high concordance (98%) with clinical fluorescent in situ hybridization and RNA NGS in detecting known SVs. Furthermore, Hi-C provided insight into the mechanism of SV formation, including chromothripsis and extrachromosomal DNA, and detected rearrangements between genes and regulatory regions, all of which are undetectable by RNA NGS. Lastly, SVs were detected in 71% of cases in which previous clinical methods failed to identify a driver. Of these, 14% were clinically actionable based on current medical guidelines, and an additional 14% were not in medical guidelines but involve targetable biomarkers. Current data suggest that Hi-C is a robust and accurate method for genome-wide SV analyses from FFPE tissue and can be incorporated into current clinical NGS workflows.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537013","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 Novel and Comprehensive Whole-Genome Sequencing-Based Preimplantation Genetic Testing Approach for Different Genetic Conditions.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-27 DOI: 10.1016/j.jmoldx.2025.02.002

Shuyuan Li, Chunxin Chang, Haiyan Bai, Weiping Qian, Yangyun Zou, Dandan Wu, Wenjing Hu, Yulin Chen, Tuan Li, Sijia Lu, Wen Li, Juanzi Shi, Zhiwei Liu

{"title":"A Novel and Comprehensive Whole-Genome Sequencing-Based Preimplantation Genetic Testing Approach for Different Genetic Conditions.","authors":"Shuyuan Li, Chunxin Chang, Haiyan Bai, Weiping Qian, Yangyun Zou, Dandan Wu, Wenjing Hu, Yulin Chen, Tuan Li, Sijia Lu, Wen Li, Juanzi Shi, Zhiwei Liu","doi":"10.1016/j.jmoldx.2025.02.002","DOIUrl":"10.1016/j.jmoldx.2025.02.002","url":null,"abstract":"Preimplantation genetic testing (PGT) is an essential tool for selecting embryos free of genetic abnormalities. However, current PGT methods often require separate platforms for aneuploidy (PGT-A), monogenic disorders (PGT-M), and structural rearrangements (PGT-SR), leading to increased costs and operational complexity when multiple PGT tests are needed for a single embryo. Here, we present KaryoSeq, a low-pass whole-genome sequencing-based comprehensive PGT approach that integrates PGT-A, PGT-M, and PGT-SR into a single platform. An assistant decision-making system was constructed to pre-evaluate the required sequencing depth for specific genes or regions. Clinical validation of KaryoSeq was performed on 166 blastocyst samples from 31 families previously diagnosed by using conventional PGT methods. KaryoSeq achieved 100% concordance with traditional platforms using the Infinium Asian Screening Array in combination with low-coverage whole-genome sequencing (approximately 0.1×); it also offered improved whole-genome coverage, reduced variability, and efficient simultaneous analysis of PGT-A, PGT-M, and PGT-SR at a whole-genome sequencing depth of approximately 2× for most genes. In addition, KaryoSeq identified triploidy, uniparental disomy, parental origin of copy number variations, and maternal cell contamination, further enhancing its clinical utility and efficiency in PGT applications.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536739","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

Impact and Reproducibility of In-House Targeted Next-Generation Sequencing Biomarker Testing in Non-Small-Cell Lung Cancer: An Italian Multi-Institutional Experience.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-27 DOI: 10.1016/j.jmoldx.2025.02.001

Ida Rapa, Francesca Bertola, Gaia Roversi, Davide Seminati, Federica Panebianco, Cecília Durães, Enzo Gallo, Biagio E Leone, Aldo Palange, Luisella Righi, Paolo Visca, Marco Volante, Simonetta Buglioni

{"title":"Impact and Reproducibility of In-House Targeted Next-Generation Sequencing Biomarker Testing in Non-Small-Cell Lung Cancer: An Italian Multi-Institutional Experience.","authors":"Ida Rapa, Francesca Bertola, Gaia Roversi, Davide Seminati, Federica Panebianco, Cecília Durães, Enzo Gallo, Biagio E Leone, Aldo Palange, Luisella Righi, Paolo Visca, Marco Volante, Simonetta Buglioni","doi":"10.1016/j.jmoldx.2025.02.001","DOIUrl":"10.1016/j.jmoldx.2025.02.001","url":null,"abstract":"Next-generation sequencing (NGS) allows the detection of multiple genetic targets in different tumor types. This study aimed to confirm the benefits of implementing in-house NGS testing for non-small-cell lung cancer (NSCLC) samples in molecular pathology laboratories. A multi-institutional study was conducted to evaluate the analytical performance, turnaround time, and feasibility of in-house NGS testing of 50 genes from 283 NSCLC samples. The first phase was a retrospective study with interlaboratory testing (21 samples), and the second phase was a prospective study with intralaboratory testing (262 samples). The retrospective study showed a 100% sequencing success rate for DNA and RNA, high interlaboratory concordance (95.2%), and a strong correlation (R2 = 0.94) between observed and expected single-nucleotide variant/insertion and/or deletion variant allele fraction. The prospective study showed a sequencing success rate of 99.2% for DNA and 98% for RNA. NGS identified 285 relevant variants (81.1% single-nucleotide variants/insertion and/or deletion variants, 9.8% copy number variants, and 9.1% gene fusions). Co-mutations with potential clinical relevance were detected in 20.5% of samples positive for the main oncogenic drivers in NSCLC. Additionally, 11% of samples wild type for the main oncogenic drivers carried alterations in other relevant genes. The in-house NGS testing had a median turnaround time from sample processing to molecular report of 4 days. This study demonstrates the advantages of implementing in-house NGS testing in molecular pathology laboratories.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537514","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

Reviewer Acknowledgment

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-24 DOI: 10.1016/j.jmoldx.2025.01.001

引用次数: 0

Retaining Clinical Genomics Technologists in the Post–COVID-19 Era

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-24 DOI: 10.1016/j.jmoldx.2024.10.005

Marco L. Leung , Barbara Anderson

引用次数: 0

Repurposing the Whole Expression Transcriptome Assay for the Genetic Diagnosis of T-Cell Acute Lymphoblastic Leukemia and Lymphoma.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-19 DOI: 10.1016/j.jmoldx.2025.01.006

Valentina Bardelli, Silvia Arniani, Valentina Pierini, Carlotta Nardelli, Caterina Matteucci, Anair Graciela Lema Fernandez, Maria Crocioni, Marco Cerrano, Prassede Salutari, Cristina Papayanidis, Silvia Trappolini, Fabio Giglio, Sara Mastaglio, Patrizia Zappasodi, Crescenza Pasciolla, Marzia Defina, Matteo Piccini, Giuseppe Lanzarone, Danika Di Giacomo, Simona Sica, Lindsey E Montefiori, Charles G Mullighan, Cristina Mecucci, Roberta La Starza

{"title":"Repurposing the Whole Expression Transcriptome Assay for the Genetic Diagnosis of T-Cell Acute Lymphoblastic Leukemia and Lymphoma.","authors":"Valentina Bardelli, Silvia Arniani, Valentina Pierini, Carlotta Nardelli, Caterina Matteucci, Anair Graciela Lema Fernandez, Maria Crocioni, Marco Cerrano, Prassede Salutari, Cristina Papayanidis, Silvia Trappolini, Fabio Giglio, Sara Mastaglio, Patrizia Zappasodi, Crescenza Pasciolla, Marzia Defina, Matteo Piccini, Giuseppe Lanzarone, Danika Di Giacomo, Simona Sica, Lindsey E Montefiori, Charles G Mullighan, Cristina Mecucci, Roberta La Starza","doi":"10.1016/j.jmoldx.2025.01.006","DOIUrl":"10.1016/j.jmoldx.2025.01.006","url":null,"abstract":"Unlike other cases of acute leukemia, the diagnosis of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is uniquely based on morphology and flow cytometry. Although the genomic background has been broadly uncovered, the large spectrum of genes involved and the variability of the molecular mechanisms underlying gene deregulation have delayed the introduction of molecular cytogenetics into diagnostic flowcharts. To overcome these limitations and implement a genetic diagnosis of T-ALL/LBLs, a whole transcriptome expression assay (WTEa) was repurposed as a \"priority test\" to classify T-ALL/LBLs into the major genetic subtypes. A WTEa classifier based on a set of 312 probes on 215 T-ALL/LBLs was set up and applied, which properly assigned >95% of cases with subtype-defining alterations to the corresponding subgroups (ie, TAL/LMO, HOXA, TLX1, TLX3, BCL11B). It pinpointed cases that harbored cryptic alterations, such as noncoding mutations that generate new enhancer at TAL1 and LMO2 loci (8% of TAL/LMO), and duplications of noncoding element downstream BCL11B (BETA) (18% of BCL11B). It was also suitable to classify lymphoma cases for which only formalin-fixed embedded tissues were available, as confirmed in cases harboring TLX1 or TLX3 rearrangements, and distinguished new putative subtypes. WTEa offers a unifying tool to provide a genetic classification of T-ALL/LBLs. If introduced in multicenter prospective studies, it will facilitate evaluation of the clinical impact of genetic classification.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472983","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 Perspective on Artificial Intelligence for Molecular Pathologists.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-13 DOI: 10.1016/j.jmoldx.2025.01.005

Timothy J O'Leary, Brendan J O'Leary, Dianne P O'Leary

引用次数: 0

Biomimetic Digital Twins and Multiomics

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-13 DOI: 10.1016/j.jmoldx.2024.12.012

William G. Kearns , Joe Glick , Lawrence Baisch , Andrew Benner , Dalton Brough , Luke Du , Chandra Germain , Laura Kearns , Georgios Stamoulis

{"title":"Biomimetic Digital Twins and Multiomics","authors":"William G. Kearns , Joe Glick , Lawrence Baisch , Andrew Benner , Dalton Brough , Luke Du , Chandra Germain , Laura Kearns , Georgios Stamoulis","doi":"10.1016/j.jmoldx.2024.12.012","DOIUrl":"10.1016/j.jmoldx.2024.12.012","url":null,"abstract":"<div><div>The National Academies of Sciences, Engineering, and Medicine issued a report on December 15, 2023, “Foundational Research Gaps and Future Directions for Digital Twins.” This described the importance of using biomimetic digital twins and multiomics in research. These were incorporated in the current analysis of patients with rheumatoid arthritis (RA). Exome sequencing, genotype-phenotype ranking, and biomimetic digital twin analysis were used to identify five pathogenic and one likely pathogenic DNA variants in patient samples analyzed, which were absent from controls. The variants identified in these genes, P2RX7, HTRA2, PTPN22, FLG, CD46, and EIF4G1, play a role in the development of RA. Additionally, 3172 variants of unknown clinical significance (VUSs) were identified in patient samples, which were absent from controls. All VUSs appeared to be associated with RA. Hidden or dark data were identified from six genes. These genes, often found in patient samples, included HIF1A, HLA-DOA, PTGER3, HIPK3, TGFBR3, and HIF1A-AS3. VUSs identified in genes HIF1A, HLA-DOA, PTGER3, and HIPK3 were directly related to the pathogenesis of RA, whereas VUSs identified in genes TGFBR3 and HIF1A-AS3 were indirectly related. The current results suggest that biomimetic digital twins and multiomics can provide further insight into the development of RA. This may also potentially help with the process of reclassifying VUSs. The reclassification of VUSs will play a critical role in complex molecular diagnostics and drug development.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 4","pages":"Pages 256-269"},"PeriodicalIF":3.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426565","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