Journal of Molecular Diagnostics最新文献_第3页

The Correlation between Plasma Circulating Tumor DNA and Radiographic Tumor Burden 血浆循环肿瘤 DNA 与放射肿瘤负荷之间的相关性。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-22 DOI: 10.1016/j.jmoldx.2024.07.001

Evan M. Alexander , Hunter A. Miller , Michael E. Egger , Melissa L. Smith , Kavitha Yaddanapudi , Mark W. Linder

{"title":"The Correlation between Plasma Circulating Tumor DNA and Radiographic Tumor Burden","authors":"Evan M. Alexander , Hunter A. Miller , Michael E. Egger , Melissa L. Smith , Kavitha Yaddanapudi , Mark W. Linder","doi":"10.1016/j.jmoldx.2024.07.001","DOIUrl":"10.1016/j.jmoldx.2024.07.001","url":null,"abstract":"<div><div>Conventional blood-based biomarkers and radiographic imaging are excellent for use in monitoring different aspects of malignant disease, but given their specific shortcomings, their integration with other, complementary markers such as plasma circulating tumor DNA (ctDNA) will be beneficial toward a precision medicine–driven future. Plasma ctDNA analysis utilizes the measurement of cancer-specific molecular alterations in a variety of bodily fluids released by dying tumor cells to monitor and profile response to therapy, and is being employed in several clinical scenarios. Plasma concentrations of ctDNA have been reported to correlate with tumor burden. However, the strength of this association is generally poor and highly variable, confounding the interpretation of longitudinal plasma ctDNA measurements in conjunction with routine radiographic assessments. Herein is discussed what is currently understood with respect to the fundamental characteristics of tumor growth that dictate plasma ctDNA concentrations, with a perspective on its interpretation in conjunction with radiographically determined tumor burden assessments.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057159","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

Accuracy of cobas MTB and MTB-RIF/INH for Detection of Mycobacterium tuberculosis and Drug Resistance cobas MTB 和 MTB-RIF/INH 检测结核杆菌和耐药性的准确性。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.05.004

{"title":"Accuracy of cobas MTB and MTB-RIF/INH for Detection of Mycobacterium tuberculosis and Drug Resistance","authors":"","doi":"10.1016/j.jmoldx.2024.05.004","DOIUrl":"10.1016/j.jmoldx.2024.05.004","url":null,"abstract":"<div><p>This study evaluated the performance of cobas MTB and cobas MTB-RIF/INH for the diagnosis of tuberculosis and detection of rifampicin (RIF) and isoniazid (INH) resistance. Adults presenting with pulmonary tuberculosis symptoms were recruited in South Africa, Moldova, and India. Performance of cobas MTB was assessed against culture, whereas cobas MTB-RIF/INH was assessed using phenotypic drug susceptibility testing and whole-genome sequencing as composite reference standards. Xpert MTB/RIF (Xpert) or Xpert MTB/RIF Ultra (Ultra) was used as a comparator. The overall sensitivity and specificity of cobas MTB were 95% (95% CI, 93%–96%) and 96% (95% CI, 95%–97%). Among smear-negatives, the sensitivity of cobas MTB was 75% (95% CI, 66%–83%). Among participants tested with both cobas MTB and Xpert, sensitivity was 96% (95% CI, 94%–97%) for cobas MTB and 95% (95% CI, 93%–97%) for Xpert. Among participants tested with both cobas MTB and Ultra, sensitivity was 88% (95% CI, 81%–92%) for cobas MTB and 89% (95% CI, 83%–93%) for Ultra. Sensitivity and specificity of cobas MTB-RIF/INH for RIF and INH detection were 90% (95% CI, 84%–94%) and 100% (95% CI, 99%–100%), and 89% (95% CI, 84%–93%) and 99.5% (95% CI, 98%–100%), respectively. The cobas MTB and cobas MTB-RIF/INH assays exhibited high performance in a diverse population and present a suitable option for molecular detection of tuberculosis and RIF and INH resistance.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Open-Source Bioinformatic Pipeline to Improve PMS2 Genetic Testing Using Short-Read NGS Data 利用短读数 NGS 数据改进 PMS2 基因测试的开源生物信息学管道。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.05.005

{"title":"Open-Source Bioinformatic Pipeline to Improve PMS2 Genetic Testing Using Short-Read NGS Data","authors":"","doi":"10.1016/j.jmoldx.2024.05.005","DOIUrl":"10.1016/j.jmoldx.2024.05.005","url":null,"abstract":"<div><p>The molecular diagnosis of mismatch repair–deficient cancer syndromes is hampered by difficulties in sequencing the <em>PMS2</em> gene, mainly owing to the PMS2CL pseudogene. Next-generation sequencing short reads cannot be mapped unambiguously by standard pipelines, compromising variant calling accuracy. This study aimed to provide a refined bioinformatic pipeline for <em>PMS2</em> mutational analysis and explore <em>PMS2</em> germline pathogenic variant prevalence in an unselected hereditary cancer (HC) cohort. <em>PMS2</em> mutational analysis was optimized using two cohorts: 192 unselected HC patients for assessing the allelic ratio of paralogous sequence variants, and 13 samples enriched with <em>PMS2</em> (likely) pathogenic variants screened previously by long-range genomic DNA PCR amplification. Reads were forced to align with the <em>PMS2</em> reference sequence, except those corresponding to exon 11, where only those intersecting gene-specific invariant positions were considered. Afterward, the refined pipeline's accuracy was validated in a cohort of 40 patients and used to screen 5619 HC patients. Compared with our routine diagnostic pipeline, the PMS2_vaR pipeline showed increased technical sensitivity (0.853 to 0.956, respectively) in the validation cohort, identifying all previously <em>PMS2</em> pathogenic variants found by long-range genomic DNA PCR amplification. Fifteen HC cohort samples carried a pathogenic <em>PMS2</em> variant (15 of 5619; 0.285%), doubling the estimated prevalence in the general population. The refined open-source approach improved <em>PMS2</em> mutational analysis accuracy, allowing its inclusion in the routine next-generation sequencing pipeline streamlining <em>PMS2</em> screening.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001181/pdfft?md5=91683b4368460b158919e0c187d84829&pid=1-s2.0-S1525157824001181-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analytical Validation of the Multitarget Stool RNA Test for Colorectal Cancer Screening 用于大肠癌筛查的多靶点粪便 RNA 检测的分析验证。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.05.001

Erica K. Barnell , Jack Land , Kimberly Kruse , Maya C. Scott , Ben Wedeking , Catherine Morrison , Clayton Grass , Ann Zuniga , Elizabeth M. Wurtzler , Eric J. Duncavage

{"title":"Analytical Validation of the Multitarget Stool RNA Test for Colorectal Cancer Screening","authors":"Erica K. Barnell , Jack Land , Kimberly Kruse , Maya C. Scott , Ben Wedeking , Catherine Morrison , Clayton Grass , Ann Zuniga , Elizabeth M. Wurtzler , Eric J. Duncavage","doi":"10.1016/j.jmoldx.2024.05.001","DOIUrl":"10.1016/j.jmoldx.2024.05.001","url":null,"abstract":"<div><p>The multitarget stool RNA (mt-sRNA) test (ColoSense) is a noninvasive diagnostic test that screens for colorectal cancer and advanced adenomas in average-risk individuals aged 45 years and older. The mt-sRNA test incorporates a commercially available fecal immunochemical test, concentration of eight RNA transcripts, and participant-reported smoking status. As part of the CRC-PREVENT (Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test) clinical trial, 12 analytical validation studies were conducted to assess analytical sensitivity, linearity, precision, interfering substances, cross-reactivity, carry-over, cross-contamination, and robustness. Analytical validation of the mt-sRNA test demonstrated limit of blank, limit of detection, and limit of quantification of <0.6, <0.7, and ≤2.5 copies/μL for all markers, respectively. The mt-sRNA test demonstrated linearity between 2.5 and 2500 copies/μL, and <20% coefficient of variation, and/or ≥95% concordance with regard to precision, interfering substances, carry-over, cross-contamination, and robustness. There was no significant impact of cross-reactivity from non–colorectal cancer diseases. These data provide a framework for laboratories to complete analytical validation for RNA-based panels that require premarket approval as a class III medical device from the US Food and Drug Administration.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001004/pdfft?md5=5a002dccd0c0f55c43f0c66aa9dd43d4&pid=1-s2.0-S1525157824001004-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Economic Impact of Whole Genome Sequencing and Whole Transcriptome Sequencing Versus Routine Diagnostic Molecular Testing to Stratify Patients with B-Cell Acute Lymphoblastic Leukemia 全基因组测序和全转录组测序与常规诊断分子检测对 B 细胞急性淋巴细胞白血病患者分层的经济影响。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.04.006

Martin Vu , Koen Degeling , Georgina L. Ryland , Oliver Hofmann , Ashley P. Ng , David Westerman , Maarten J. IJzerman

{"title":"Economic Impact of Whole Genome Sequencing and Whole Transcriptome Sequencing Versus Routine Diagnostic Molecular Testing to Stratify Patients with B-Cell Acute Lymphoblastic Leukemia","authors":"Martin Vu , Koen Degeling , Georgina L. Ryland , Oliver Hofmann , Ashley P. Ng , David Westerman , Maarten J. IJzerman","doi":"10.1016/j.jmoldx.2024.04.006","DOIUrl":"10.1016/j.jmoldx.2024.04.006","url":null,"abstract":"<div><p>Whole genome and whole transcriptome sequencing (WGTS) can accurately distinguish B-cell acute lymphoblastic leukemia (B-ALL) genomic subtypes. However, whether this is economically viable remains unclear. This study compared the direct costs and molecular subtype classification yield using different testing strategies for WGTS in adolescent and young adult/adult patients with B-ALL. These approaches were: (1) combined <em>BCR::ABL1</em> by fluorescence <em>in situ</em> hybridization (FISH) + WGTS for all patients; and (2) sequential <em>BCR::ABL1</em> FISH + WGTS contingent on initial <em>BCR::ABL1</em> FISH test outcome. The cost of routine diagnostic testing was estimated using Medicare or hospital fees, and the additional cost of WGTS was evaluated from the health care provider perspective using time-driven activity-based costing with resource identification elicited from experts. Molecular subtype classification yield data were derived from literature sources. Parameter uncertainty was assessed through deterministic sensitivity analysis; additional scenario analyses were performed. The total per patient cost of WGTS was $4319 (all costs reported in US dollars); consumables accounted for 74% of the overall cost, primarily driven by sequencing-related consumables. The incremental cost per additional patient categorized into molecular subtype was $8498 for combined <em>BCR::ABL1</em> FISH + WGTS for all patients and $5656 for initial <em>BCR::ABL1</em> FISH + WGTS for select patients compared with routine diagnostic testing. A reduction in the consumable costs of WGTS or an increase in the yield of molecular subtype classification is favorable.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767957","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

Recommendations for Tumor Mutational Burden Assay Validation and Reporting 肿瘤突变负荷测定验证和报告建议：分子病理学协会、美国病理学家学会和癌症免疫疗法学会的联合共识建议》（Association for Molecular Pathology, College of American Pathologists, and Society for Immunotherapy of Cancer）。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.05.002

{"title":"Recommendations for Tumor Mutational Burden Assay Validation and Reporting","authors":"","doi":"10.1016/j.jmoldx.2024.05.002","DOIUrl":"10.1016/j.jmoldx.2024.05.002","url":null,"abstract":"<div><p>Tumor mutational burden (TMB) has been recognized as a predictive biomarker for immunotherapy response in several tumor types. Several laboratories offer TMB testing, but there is significant variation in how TMB is calculated, reported, and interpreted among laboratories. TMB standardization efforts are underway, but no published guidance for TMB validation and reporting is currently available. Recognizing the current challenges of clinical TMB testing, the Association for Molecular Pathology convened a multidisciplinary collaborative working group with representation from the American Society of Clinical Oncology, the College of American Pathologists, and the Society for the Immunotherapy of Cancer to review the laboratory practices surrounding TMB and develop recommendations for the analytical validation and reporting of TMB testing based on survey data, literature review, and expert consensus. These recommendations encompass pre-analytical, analytical, and postanalytical factors of TMB analysis, and they emphasize the relevance of comprehensive methodological descriptions to allow comparability between assays.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001156/pdfft?md5=1f258a6b15d6b3f5b04704ed658b82e9&pid=1-s2.0-S1525157824001156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Colorectal Cancer Screening 大肠癌筛查：增加选择。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.05.003

引用次数: 0

Performance Evaluation of a Commercial Automated Library Preparation System for Clinical Microbial Whole-Genome Sequencing Assays 用于临床微生物全基因组测序测定的商用自动文库制备系统的性能评估。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.05.006

{"title":"Performance Evaluation of a Commercial Automated Library Preparation System for Clinical Microbial Whole-Genome Sequencing Assays","authors":"","doi":"10.1016/j.jmoldx.2024.05.006","DOIUrl":"10.1016/j.jmoldx.2024.05.006","url":null,"abstract":"<div><p>Next-generation sequencing (NGS) has proven clinical utility on disease management and serves as an important tool for genomic surveillance. Currently, hurdles surrounding its implementation, namely the complex and demanding analytical workflows, have impeded its widespread use in many laboratories. To address this challenge, the UCLA Molecular Microbiology and Pathogen Genomics Laboratory evaluated the performance of the Tecan MagicPrep NGS system, a commercial automated solution for library preparation for clinical whole-genome sequencing assays, against the Illumina Nextera DNA Flex Library Prep. Using 35 unique organisms (28 bacteria and 7 fungi) for various clinical applications, including microbial identification and genomic characterization, we compared the quantity and quality of the prepared libraries and the resulting sequences, and concordance of the overall results. We also assessed the impact of its implementation on laboratory workflow. The MagicPrep NGS produced higher library concentrations with smaller sizes, and correspondingly, higher molarity. Quality metrics of the sequences, however, demonstrated no significant impact on the overall results, producing 100% concordance with the reference method. Importantly, workflow analysis showed 5 hours less hands-on time per run with more flexibility. This evaluation study indicates that performance of the MagicPrep NGS is comparable to the Nextera DNA Flex with the added benefit of improving workflow efficiency and reducing labor for performing routine clinical microbial whole-genome sequencing tests.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001193/pdfft?md5=ec16f54f7fb1d2b797624fe26f3838ca&pid=1-s2.0-S1525157824001193-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Implementation of a High-Accuracy Targeted Gene Expression Panel for Clinical Care 在临床护理中实施高精度靶向基因表达检测。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.04.005

{"title":"Implementation of a High-Accuracy Targeted Gene Expression Panel for Clinical Care","authors":"","doi":"10.1016/j.jmoldx.2024.04.005","DOIUrl":"10.1016/j.jmoldx.2024.04.005","url":null,"abstract":"<div><p>This study describes the validation of a clinical RNA expression panel with evaluation of concordance between gene copy gain by a next-generation sequencing (NGS) assay and high gene expression by an RNA expression panel. The RNA Salah Targeted Expression Panel (RNA STEP) was designed with input from oncologists to include 204 genes with utility for clinical trial prescreening and therapy selection. RNA STEP was validated with the nanoString platform using remnant formalin-fixed, paraffin-embedded–derived RNA from 102 patients previously tested with a validated clinical NGS panel. The repeatability, reproducibility, and concordance of RNA STEP results with NGS results were evaluated. RNA STEP demonstrated high repeatability and reproducibility, with excellent correlation (<em>r</em> > 0.97, <em>P</em> < 0.0001) for all comparisons. Comparison of RNA STEP high gene expression (log2 ratio ≥ 2) versus NGS DNA-based gene copy number gain (copies ≥ 5) for 38 mutually covered genes revealed an accuracy of 93.0% with a positive percentage agreement of 69.4% and negative percentage agreement of 93.8%. Moderate correlation was observed between platforms (<em>r</em> = 0.53, <em>P</em> < 0.0001). Concordance between high gene expression and gene copy number gain varied by specific gene, and some genes had higher accuracy between assays. Clinical implementation of RNA STEP provides gene expression data complementary to NGS and offers a tool for prescreening patients for clinical trials.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082655","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

Comparative Analysis of Gene Expression Analysis Methods for RNA in Situ Hybridization Images RNA 原位杂交图像基因表达分析方法的比较分析。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-26 DOI: 10.1016/j.jmoldx.2024.06.010

Valeria Ariotta , Eros Azzalini , Vincenzo Canzonieri , Sampsa Hautaniemi , Serena Bonin

引用次数: 0