Journal of Molecular Diagnostics最新文献_第10页

Clinical Performance Evaluation of a Tiling Amplicon Panel for Whole-Genome Sequencing of Respiratory Syncytial Virus 呼吸道合胞病毒全基因组测序切片扩增子面板的临床性能评价。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-09-01 Epub Date: 2025-06-19 DOI: 10.1016/j.jmoldx.2025.05.005

B. Ethan Nunley , Amelia Weixler , Hyeong Geon Kim , Hong Xie , Jaydee Sereewit , Pooneh Hajian , Sean Ellis , Margaret G. Mills , Ailyn C. Pérez-Osorio , Stephanie Goya , Jolene Gov , Rebecca Dewar , Goncalo Fernandes , Kate E. Templeton , Daniel M. Maloney , Alexander L. Greninger , Pavitra Roychoudhury

{"title":"Clinical Performance Evaluation of a Tiling Amplicon Panel for Whole-Genome Sequencing of Respiratory Syncytial Virus","authors":"B. Ethan Nunley , Amelia Weixler , Hyeong Geon Kim , Hong Xie , Jaydee Sereewit , Pooneh Hajian , Sean Ellis , Margaret G. Mills , Ailyn C. Pérez-Osorio , Stephanie Goya , Jolene Gov , Rebecca Dewar , Goncalo Fernandes , Kate E. Templeton , Daniel M. Maloney , Alexander L. Greninger , Pavitra Roychoudhury","doi":"10.1016/j.jmoldx.2025.05.005","DOIUrl":"10.1016/j.jmoldx.2025.05.005","url":null,"abstract":"<div><div>Accurate genomic characterization of respiratory syncytial virus (RSV) is crucial for studies of epidemiology and viral evolution, including monitoring potential escape from newly authorized vaccines and prophylactic monoclonal antibodies. A viral genome tiling amplicon panel (UW-ARTIC) was adapted to develop a custom bioinformatic pipeline for high-throughput, cost-effective sequencing of both RSV-A and RSV-B subgroups. Genome acceptability criteria were established and the performance characteristics of the panel were determined, including assay sensitivity, specificity, breadth of genome recovery, accuracy, and precision, using contrived and remnant clinical specimens. High-quality genomes (>95% genome completeness; >500× and >1000× average depth for whole genome and fusion gene, respectively) were recovered from samples with cycle threshold ≤ 30 (approximately 594 and 2004 copies per reaction for RSV-A and RSV-B, respectively). Minor variants were accurately identified at >5% allele frequency. The assay showed high accuracy when compared with Sanger, shotgun metagenomic, and hybridization capture-based sequencing, as well as high repeatability and reproducibility. The UW-ARTIC RSV panel has utility for cost-effective RSV genome recovery in public health, clinical, and research applications. It has been used to generate US Food and Drug Administration–reportable data for clinical trials of RSV antiviral products, with robust performance in global samples from as recently as the 2023/2024 season. Continued genomic surveillance and future updates to primers will be essential for continued recovery of genomes as RSV continues to evolve.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 9","pages":"Pages 819-831"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340561","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

Screening G6PD Mutations in Blood Donors by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry with High-Throughput and Multiple Targets 基质辅助激光解吸/电离飞行时间质谱高通量多靶点筛查献血者G6PD突变

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-09-01 Epub Date: 2025-06-19 DOI: 10.1016/j.jmoldx.2025.05.004

Ziyan Li , Zhenyi Huang , Mengxi Li , Yunshan Cao , Yating Li , Jinlv Liu , Suping Zhong , Lijuan Lin , Yanping Fang , Zhaoying Su , Yongxin Huang , Wanjun Zhou , Lingxiao Jiang

{"title":"Screening G6PD Mutations in Blood Donors by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry with High-Throughput and Multiple Targets","authors":"Ziyan Li , Zhenyi Huang , Mengxi Li , Yunshan Cao , Yating Li , Jinlv Liu , Suping Zhong , Lijuan Lin , Yanping Fang , Zhaoying Su , Yongxin Huang , Wanjun Zhou , Lingxiao Jiang","doi":"10.1016/j.jmoldx.2025.05.004","DOIUrl":"10.1016/j.jmoldx.2025.05.004","url":null,"abstract":"<div><div>Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited disorder worldwide and is particularly prevalent in historically malaria-endemic countries. This study established a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) assay for <em>G6PD</em> mutation detection. This MALDI-TOF-MS assay with single-base extension was developed to efficiently and accurately test 19 common <em>G6PD</em> variants in the Chinese population. The MALDI-TOF-MS assay was used to analyze a total of 2205 peripheral blood samples, including 1111 normal individuals and 1094 <em>G6PD</em> gene mutation carriers. All 2205 sample results were validated by Sanger sequencing in a blinded study. The MALDI-TOF-MS assay developed in this study was applied to detect <em>G6PD</em> mutations in 300 uncharacterized blood donor samples, of which 17 (5.67%) were found to carry <em>G6PD</em> gene mutations. The baseline and follow-up characteristics of the 17 blood donors were summarized. In this study, a MALDI-TOF-MS assay was applied to detect common <em>G6PD</em> mutations in samples from blood donors in Guangdong, China, which provided a new concept for establishing the information regarding the blood bank database of G6PD-deficient donors.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 9","pages":"Pages 832-840"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340562","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

Value of Molecular Autopsy in Suspected Sudden Cardiac Death in the Young 分子解剖在疑似青年心源性猝死中的价值。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-09-01 Epub Date: 2025-06-19 DOI: 10.1016/j.jmoldx.2025.05.006

Mònica Coll , Mireia Alcalde , Anna Fernández-Falgueras , Anna Iglesias , Laia Nogué-Navarro , Coloma Tiron , Oscar Campuzano , Marisa Ortega , Santiago Crespo , Eneko Barberia , Ramon Brugada

{"title":"Value of Molecular Autopsy in Suspected Sudden Cardiac Death in the Young","authors":"Mònica Coll , Mireia Alcalde , Anna Fernández-Falgueras , Anna Iglesias , Laia Nogué-Navarro , Coloma Tiron , Oscar Campuzano , Marisa Ortega , Santiago Crespo , Eneko Barberia , Ramon Brugada","doi":"10.1016/j.jmoldx.2025.05.006","DOIUrl":"10.1016/j.jmoldx.2025.05.006","url":null,"abstract":"<div><div>Genetic testing, as part of the medicolegal autopsy in cases of suspected sudden cardiac death, has been recommended for several years; however, it is rarely performed. The aim was to assess the value of postmortem genetic testing in unexplained sudden death in the young. This is a prospective study including all cases with unexplained natural sudden death cases in individuals aged ≤50 years undergoing a legal autopsy. Postmortem genetic testing was routinely performed in cases aged ≤35 years and aged >35 years only when no cause of death was identified or there was suspicion of a possible inherited cardiac phenotype after a complete autopsy. In cases aged ≤35 years, genetic testing showed a positivity rate of 7.6%. The most striking finding has been the positivity rate of thoracic aorta aneurysms and myocarditis cases at 33%. In cases between the ages of 36 and 50 years, the positivity rate was 4.9%. If this group was approached with direct genetic analysis, as was done with the younger cohort, the yield of positive genetic testing would decrease to 2.5%. This is the largest study of postmortem genetic testing in the young to date, and the first to address its value in consecutive cases, free of selection bias.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 9","pages":"Pages 859-868"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340563","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 Assessment of Next-Generation Sequencing Probe Reproducibility in Short-Read Sequencing (ClinRay) Using Digital Twins 使用数字双胞胎的短读测序（ClinRay）中新一代测序探针可重复性的临床评估

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-09-01 Epub Date: 2025-08-25 DOI: 10.1016/j.jmoldx.2025.06.001

Rohan Gnanaolivu , Neiladri Saha , Noemi Vidal-Folch , Jiayu Tan , Feng Li , Shawn McClelland , Zhiyv Niu , Devin Oglesbee , Chen Wang

{"title":"Clinical Assessment of Next-Generation Sequencing Probe Reproducibility in Short-Read Sequencing (ClinRay) Using Digital Twins","authors":"Rohan Gnanaolivu , Neiladri Saha , Noemi Vidal-Folch , Jiayu Tan , Feng Li , Shawn McClelland , Zhiyv Niu , Devin Oglesbee , Chen Wang","doi":"10.1016/j.jmoldx.2025.06.001","DOIUrl":"10.1016/j.jmoldx.2025.06.001","url":null,"abstract":"<div><div>Short-read next-generation sequencing is widely used for clinical diagnosis but faces limitations in accurately detecting variants in complex genomic regions, such as segmental duplications, guanine-cytosine rich areas, and repeat sequences. These challenging regions comprise only 3% to 5% of the exome, yet their stochastic library preparation and bioinformatics analysis impacts variant detection reproducibility. Evaluating reproducibility is time-consuming, and variants in these regions require validation through sequencing replicates and using orthogonal methods like long-range PCR or Sanger sequencing, thereby increasing costs and turnaround times for clinical laboratories. To address these challenges, ClinRay was developed; it is a novel, generalizable bioinformatics method that uses the concept of digital twins to synthetically enhance the data distribution for variants in regions with suspected poor reproducibility. ClinRay predicts the reproducibility of detected variants by short-read next-generation sequencing probes in these difficult-to-sequence genomic regions. The model was developed using alignment data from the binary format of the sequence alignment/map files of eight replicates of the Genome in a Bottle HG002 Coriell cell and publicly available genomic context annotation resources. The model achieved an area under the receiver-operating characteristic curve of 0.89 (95% CI, 0.88–0.90) on the test data and 0.85 (95% CI, 0.84–0.86) on an independent validation data set.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 9","pages":"Pages 899-912"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902425","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 Comparative Study of Medium-Coverage Genome Sequencing and SNP Array Technology in Identifying Chromosomal Abnormalities to Advance Prenatal and Postnatal Diagnosis 中覆盖基因组测序和SNP阵列技术在染色体异常识别中的比较研究，以促进产前和产后诊断。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-08-01 Epub Date: 2025-06-06 DOI: 10.1016/j.jmoldx.2025.04.009

Jialun Pang , Lin Zhou , Jiancheng Hu , Hanzhe Kuang , Hui Xi , Na Ma , Shuting Yang , Wenxian Yu , Yanan Zhang , Qian Zhang , Victor Wei Zhang , Jing Chen , Ying Peng

{"title":"A Comparative Study of Medium-Coverage Genome Sequencing and SNP Array Technology in Identifying Chromosomal Abnormalities to Advance Prenatal and Postnatal Diagnosis","authors":"Jialun Pang , Lin Zhou , Jiancheng Hu , Hanzhe Kuang , Hui Xi , Na Ma , Shuting Yang , Wenxian Yu , Yanan Zhang , Qian Zhang , Victor Wei Zhang , Jing Chen , Ying Peng","doi":"10.1016/j.jmoldx.2025.04.009","DOIUrl":"10.1016/j.jmoldx.2025.04.009","url":null,"abstract":"<div><div>This study compared the performance of 5-fold genome sequencing (GS) with single nucleotide polymorphism (SNP) array technology in detecting chromosomal abnormalities, particularly in the context of prenatal and postnatal diagnostics. A total of 42 samples, previously analyzed by SNP array, were re-examined using 5-fold GS to evaluate the detection of clinically significant copy number variations (CNVs), mosaicism, and absence of heterozygosity (AOH). The results revealed a 100% concordance between the two methods for the identification of clinically relevant CNVs, with both technologies detecting similar CNV size ranges. However, 5-fold GS demonstrated better precision in defining CNV breakpoints and exhibited a lower false-positive rate, as confirmed by quantitative PCR validation. Additionally, 5-fold GS detected mosaicism with comparable sensitivity to SNP array, capturing mosaic levels as low as 17%, whereas SNP array identified levels between 15% and 84%. For AOH detection, 5-fold GS identified all candidate AOH regions with a slightly better sensitivity, achieving a detection size limit of 4.8 Mb compared with SNP array's 5.08 Mb. Overall, 5-fold GS shows potential as a reliable method for chromosomal abnormality detection, offering high accuracy and clinical utility in both prenatal and postnatal genetic testing.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 8","pages":"Pages 736-746"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250605","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 Human Papillomavirus Genotyping by Oxford Nanopore Sequencing in Formalin-Fixed, Paraffin-Embedded Tissues and ThinPrep Anal and Gynecologic Samples 牛津纳米孔测序在FFPE组织和ThinPrep肛门和妇科样本中的HPV基因分型验证。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-08-01 Epub Date: 2025-06-05 DOI: 10.1016/j.jmoldx.2025.04.010

Carolina Hernandez , Luz H. Patiño , Milena Camargo , Ching Yi Wang , Feng Chen , Bernadette Liggayu , Liyong Cao , Carlos Cordon-Cardo , Emilia M. Sordillo , Alberto Paniz-Mondolfi , Juan D. Ramírez

{"title":"Validation of Human Papillomavirus Genotyping by Oxford Nanopore Sequencing in Formalin-Fixed, Paraffin-Embedded Tissues and ThinPrep Anal and Gynecologic Samples","authors":"Carolina Hernandez , Luz H. Patiño , Milena Camargo , Ching Yi Wang , Feng Chen , Bernadette Liggayu , Liyong Cao , Carlos Cordon-Cardo , Emilia M. Sordillo , Alberto Paniz-Mondolfi , Juan D. Ramírez","doi":"10.1016/j.jmoldx.2025.04.010","DOIUrl":"10.1016/j.jmoldx.2025.04.010","url":null,"abstract":"<div><div>Human papillomavirus (HPV) is linked to various cancers, including cervical, anal, and head and neck cancers. Conventional methods for HPV genotyping and commercial platforms are limited to detecting high-risk HPV genotypes primarily in gynecologic samples. Because of changing trends in the epidemiology and pathogenesis, there is a growing need for HPV genotyping techniques applicable to emerging clinical contexts involving diverse sample types, such as head and neck or anal samples, particularly for formalin-fixed, paraffin-embedded (FFPE) tissues. This study aimed to validate amplicon-based sequencing with Oxford Nanopore Technologies (ONT) for the detection and genotyping of HPV in 181 samples, including FFPE head and neck samples, and ThinPrep liquid-based cytology samples from anal and gynecologic tissues. Sanger sequencing was used as a reference for genotyping accuracy. The ONT sequencing method demonstrated a limit of detection of 1 copy/μL for HPV16 and HPV18. Perfect agreement (κ coefficient = 1.0) was observed for HPV detection across all sample types. Genotyping accuracy exceeded 95%, and ONT identified additional genotypes in certain anal and gynecologic samples that were undetected by Sanger sequencing. The assay showed high reproducibility, with consistent results across intrarun and interrun analyses. This study is the first to validate ONT sequencing for HPV genotyping in FFPE head and neck samples. ONT provides a rapid, cost-effective method for comprehensive HPV genotyping in diverse sample types.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 8","pages":"Pages 757-767"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250607","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 Clinical Molecular Laboratories for Detection of Homologous Recombination Deficiency in Cancer 对检测癌症同源重组缺陷的临床分子实验室的建议：分子病理学协会、癌症护理中心协会和美国病理学家学院的联合共识建议。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-08-01 Epub Date: 2025-06-13 DOI: 10.1016/j.jmoldx.2025.05.003

Susan J. Hsiao , Destin Black , Kelly A. Devereaux , Ian S. Hagemann , Lawrence J. Jennings , Diana Mandelker , Vera A. Paulson , Michelle Shiller , Tracy L. Stockley , Eric Vail , Praveen Vikas , Anna Yemelyanova

{"title":"Recommendations for Clinical Molecular Laboratories for Detection of Homologous Recombination Deficiency in Cancer","authors":"Susan J. Hsiao , Destin Black , Kelly A. Devereaux , Ian S. Hagemann , Lawrence J. Jennings , Diana Mandelker , Vera A. Paulson , Michelle Shiller , Tracy L. Stockley , Eric Vail , Praveen Vikas , Anna Yemelyanova","doi":"10.1016/j.jmoldx.2025.05.003","DOIUrl":"10.1016/j.jmoldx.2025.05.003","url":null,"abstract":"<div><div>Homologous recombination deficiency (HRD) is a genomic feature present in some malignant neoplasms and is attributed to the failure of the homologous recombination repair pathway. Tumors with an HRD-positive status may have a distinct prognosis and/or response to therapies, including poly (ADP-ribose) polymerase inhibitors. The Association for Molecular Pathology assembled an expert panel to examine current practice and perform a scoping review of the medical literature pertaining to the molecular detection of HRD in the clinical setting. The expert panel examined the following topics: components of existing and proposed HRD and genomic instability biomarkers (including mutational signatures, loss of heterozygosity, mutations in homologous recombination repair–associated genes, and epigenetic silencing of <em>RAD51C</em>, <em>BRCA1</em>, or <em>BRCA2</em>); technical considerations for identifying genomic scars from tumor and germline next-generation sequencing results; guidelines on interpretation and caveats when reporting assessments of genomic instability and HRD scores; and the clinical significance of HRD. The panel formulated a set of expert consensus opinion recommendations regarding HRD assay design and validation to guide laboratories in developing HRD tests to ensure high-quality and reproducible results.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 8","pages":"Pages 685-704"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303456","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

Path to Health Equity and Improved Outcomes through Inclusive Sex and Gender Data Collection in Genomic Testing 通过基因组检测中包容性的性别和社会性别数据收集实现健康公平和改善结果之路。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-08-01 Epub Date: 2025-05-15 DOI: 10.1016/j.jmoldx.2025.04.004

Marco L. Leung , Ina Amarillo , Danielle Jordan , Matthew S. Lebo , Rizwan C. Naeem , David I. Suster , Robyn L. Temple-Smolkin , Cigdem H. Ussakli , Honey V. Reddi

{"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 L. 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":"<div><div>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.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 8","pages":"Pages 677-684"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","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}

引用次数: 0

Smart Nonuniformity for Calibrating Sequencing Depth of a Targeted Gene Panel to Simultaneously Detect Somatic and Germline Variants 智能非均匀性：校准目标基因面板的测序深度，同时检测体细胞和种系变异。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-08-01 Epub Date: 2025-05-15 DOI: 10.1016/j.jmoldx.2025.04.007

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

{"title":"Smart Nonuniformity for Calibrating 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":"<div><div>Targeted gene panel sequencing that measures genomic variation at different depths has potential diagnostic application. A targeted gene panel, smart nonuniformity sequencing, 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.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 8","pages":"Pages 705-712"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","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}

引用次数: 0

Standardizing Laboratory Practices in Pharmacogenomics (STRIPE) Consensus Conference 标准化药物基因组学实验室实践（STRIPE）共识会议：实验室挑战工作组报告。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-08-01 Epub Date: 2025-05-17 DOI: 10.1016/j.jmoldx.2025.04.006

Victoria M. Pratt , Betsy Bove , Raymond A. Lorenz , Annette K. Taylor , Bronwyn Ramey

引用次数: 0