Journal of Molecular Diagnostics最新文献

Concordance of whole-genome long-read sequencing with standard clinical testing for Prader-Willi and Angelman syndromes.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-01-03 DOI: 10.1016/j.jmoldx.2024.12.003

Cate R Paschal, Miranda P G Zalusky, Anita E Beck, Madelyn A Gillentine, Jaya Narayanan, Nikhita Damaraju, Joy Goffena, Sophie H R Storz, Danny E Miller

{"title":"Concordance of whole-genome long-read sequencing with standard clinical testing for Prader-Willi and Angelman syndromes.","authors":"Cate R Paschal, Miranda P G Zalusky, Anita E Beck, Madelyn A Gillentine, Jaya Narayanan, Nikhita Damaraju, Joy Goffena, Sophie H R Storz, Danny E Miller","doi":"10.1016/j.jmoldx.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2024.12.003","url":null,"abstract":"Current clinical testing approaches for individuals with suspected imprinting disorders are complex, often requiring multiple tests performed in a stepwise fashion to make a precise molecular diagnosis. We investigated whether whole-genome long-read sequencing (LRS) could be used as a single data source to simultaneously evaluate copy number variants (CNVs), single nucleotide variants (SNVs), structural variants (SVs), and differences in methylation in a cohort of individuals known to have either Prader-Willi or Angelman syndrome. We evaluated 25 individuals sequenced to an average depth of coverage of 36x on an Oxford Nanopore PromethION. A custom one-page report was generated that could be used to assess copy number, SNVs, and methylation patterns at select CpG sites within the 15q11.2-q13.1 region and prioritize candidate pathogenic variants in UBE3A. After training with three positive controls, three analysts blinded to the known clinical diagnosis arrived at the correct molecular diagnosis for 22 out of 22 cases (20 true positive, 2 negative controls). Our findings demonstrate the utility of LRS as a single, comprehensive data source for complex clinical testing, offering potential benefits such as reduced testing costs, increased diagnostic yield, and shorter turnaround times in the clinical laboratory.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933413","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 Clinical Laboratory Improvement Amendments/College of American Pathologists-Compliant Noninvasive Laboratory-Developed Test for Early Detection of Pancreatic Ductal Adenocarcinoma. 符合 CLIA/CAP 标准的无创实验室开发的胰腺导管腺癌早期检测试剂盒。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-01-01 Epub Date: 2024-11-07 DOI: 10.1016/j.jmoldx.2024.10.001

Jian Tajbakhsh, Silvana Debernardi, Oleg Blyuss, Jianhao Bai, Ruifen Weng, Simon Lo, Stephen J Pandol, Tatjana Crnogorac-Jurcevic, Nirdesh K Gupta

{"title":"A Clinical Laboratory Improvement Amendments/College of American Pathologists-Compliant Noninvasive Laboratory-Developed Test for Early Detection of Pancreatic Ductal Adenocarcinoma.","authors":"Jian Tajbakhsh, Silvana Debernardi, Oleg Blyuss, Jianhao Bai, Ruifen Weng, Simon Lo, Stephen J Pandol, Tatjana Crnogorac-Jurcevic, Nirdesh K Gupta","doi":"10.1016/j.jmoldx.2024.10.001","DOIUrl":"10.1016/j.jmoldx.2024.10.001","url":null,"abstract":"A noninvasive test for earlier detection of pancreatic cancer in individuals at higher risk is currently unavailable. We devised PancSure, a laboratory-developed test based on the protein biomarkers lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) and regenerating family member 1 β (REG1B), measured in urine by enzyme-linked immunosorbent assay, and commonly used serum/plasma carbohydrate antigen 19.9 (CA19.9), with an updated PancRISK algorithm for data interpretation. The test was validated in 565 patients: 117 asymptomatic patients without any known pancreatic condition or malignancies (21%), 242 symptomatic patients with benign pancreatic diseases (43%), and 206 patients with confirmed cancers (36%); 161 (77.5%) had stage I to II disease, and 45 (22.5%) had stage III to IV disease. PancSure passed all specifications during analytical validation and distinguishes early-stage resectable cancer from asymptomatic individuals with area under the receiver operating characteristic curve (AUC) of 0.93 (95% CI, 0.89-0.97) and 85% to 90% sensitivity (SN) and 78% to 87% specificity (SP); from symptomatic patients with AUC of 0.86 (95% CI, 0.81-0.91) and 83% to 85% SN and 72% to 83% SP; and from all noncancer patients (pooled controls) with AUC of 0.89 (95% CI, 0.84-0.93) and 83% to 85% SN and 78% to 87% SP. PancSure is a noninvasive clinical-grade test with a 48-hour turnover, ready for implementation, providing a viable solution for the earlier detection of pancreatic cancer in at-risk groups for improved patient care.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":"54-61"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631478","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

Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System. 分析社区-学术混合医疗系统中疑似骨髓增生性肿瘤的分子检测。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-01-01 Epub Date: 2024-11-07 DOI: 10.1016/j.jmoldx.2024.10.003

Andrew B Stone, Ryan J Martinez, Cade Arries, Andrew C Nelson, Bharat Thyagarajan, Sophia Yohe, Pawel Mroz

{"title":"Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System.","authors":"Andrew B Stone, Ryan J Martinez, Cade Arries, Andrew C Nelson, Bharat Thyagarajan, Sophia Yohe, Pawel Mroz","doi":"10.1016/j.jmoldx.2024.10.003","DOIUrl":"10.1016/j.jmoldx.2024.10.003","url":null,"abstract":"Testing for somatic mutations in JAK2, MPL, and CALR genes is critical in the diagnosis of myeloproliferative neoplasms (MPNs). However, this testing may have inadvertently led to increased requests to rule out MPN, including clinical situations with low pretest probability. This article examines JAK2, MPL, and CALR testing by next-generation sequencing (NGS) with the goal of formulating practical guidelines to make test use more efficient and effective. NGS results from 1482 patients tested between 2015 and March 2022 were retrieved, along with corresponding bone marrow biopsies and complete blood cell count results performed within 90 days before NGS, and 245 cases (16.5%) were positive for pathogenic variants in JAK2, MPL, or CALR genes. The findings showed an increase in the proportion of positive cases with patient age, and a statistically significant difference in red blood cell counts and platelet counts among patients with positive versus negative results. Using these factors, simple algorithms were constructed to predict positive results with a maximum sensitivity of 91%, while potentially eliminating 28% of negative test results. However, these models still failed to identify approximately 9% of patients with MPNs. Among these missed patients, many had either primary myelofibrosis or myelodysplastic syndrome/MPN. Considering a simple triage model to help guide MPN testing could represent a more cost-effective approach, particularly if missed patients could be further reduced.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":"42-53"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631496","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

Considerations for Severe Acute Respiratory Syndrome Coronavirus 2 Genomic Surveillance: A Joint Consensus Recommendation of the Association for Molecular Pathology and Association of Public Health Laboratories. SARS-CoV-2 基因组监测的考虑因素：分子病理学协会和公共卫生实验室协会的联合共识建议。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-01-01 Epub Date: 2024-10-21 DOI: 10.1016/j.jmoldx.2024.09.005

Julie W Hirschhorn, N Esther Babady, Allen Bateman, Heather M Blankenship, Jennifer Dien Bard, Kelsey Florek, Paige M K Larkin, Marie-Claire Rowlinson, Kelly Wroblewski, Donna M Wolk

{"title":"Considerations for Severe Acute Respiratory Syndrome Coronavirus 2 Genomic Surveillance: A Joint Consensus Recommendation of the Association for Molecular Pathology and Association of Public Health Laboratories.","authors":"Julie W Hirschhorn, N Esther Babady, Allen Bateman, Heather M Blankenship, Jennifer Dien Bard, Kelsey Florek, Paige M K Larkin, Marie-Claire Rowlinson, Kelly Wroblewski, Donna M Wolk","doi":"10.1016/j.jmoldx.2024.09.005","DOIUrl":"10.1016/j.jmoldx.2024.09.005","url":null,"abstract":"Next-generation sequencing (NGS) has applications in research, epidemiology, oncology, and infectious disease diagnostics. Wide variability exists in NGS wet laboratory techniques and dry laboratory analytical considerations. Thus, many questions remain unanswered when NGS methods are implemented in laboratories for infectious disease testing. Although this review is not intended to answer all questions, the most pressing questions from a public health and clinical hospital-based laboratory perspective will be addressed. The authors of this review are laboratory professionals who perform and interpret severe acute respiratory syndrome coronavirus 2 NGS results. Considerations for pre-analytical, analytical, and postanalytical NGS will be explored. This review highlights challenges for molecular laboratory professionals considering adopting or expanding NGS methods.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":"12-24"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512117","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

Establishing a Variant Allele Frequency Cutoff for Manual Curation of Medical Exome Sequencing Data. 为人工编辑医学外显子组测序数据设定变异等位基因频率临界值。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-01-01 Epub Date: 2024-10-18 DOI: 10.1016/j.jmoldx.2024.09.006

Kate Sears, Caylin Hickey, Ryan Vincent, Jennifer Stocks-Candelaria, Jason Tate, Cody Bumgardner, Shulin Zhang, Justin B Miller

{"title":"Establishing a Variant Allele Frequency Cutoff for Manual Curation of Medical Exome Sequencing Data.","authors":"Kate Sears, Caylin Hickey, Ryan Vincent, Jennifer Stocks-Candelaria, Jason Tate, Cody Bumgardner, Shulin Zhang, Justin B Miller","doi":"10.1016/j.jmoldx.2024.09.006","DOIUrl":"10.1016/j.jmoldx.2024.09.006","url":null,"abstract":"Medical exome sequencing pipelines consist of various preprocessing steps to prioritize credible causal variants before a pathologist or variant curation scientist manually interprets potential findings that are then reported to patients. The variant allele frequency (VAF), reported as the fraction of sequencing reads supporting a variant call, can be used to screen for technical artifacts, yet a specific filtering threshold has yet to be established. A total of 13,122 manually curated variants, sequenced from 289 patients using the Agilent SureSelect Focused Exome enrichment kit at the University of Kentucky Clinical Genomics laboratory from October 2019 to May 2023, were evaluated. Totals of 278 single-nucleotide polymorphisms (SNPs) and 3340 SNPs as technical artifacts are clinically reported. All reported variants had a VAF between 0.33 and 0.63, and 82% (2725/3340) of sequencing artifacts had a VAF of <0.33. It is proposed that removing SNPs in which the VAF is less than approximately 0.30 reduces manual curation time by approximately 20% while capturing all medically relevant variants in medical exome sequencing data sets.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":"36-41"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479408","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

Surveillance of Disease Progression in Metastatic Breast Cancer by Molecular Counting of Circulating Tumor DNA Using Plasma-SeqSensei Breast Cancer in Vitro Diagnostics Assay. 使用 Plasma-SeqSensei 乳腺癌体外诊断试剂盒对循环肿瘤 DNA 进行分子计数，监测转移性乳腺癌的病情进展。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-01-01 Epub Date: 2024-11-07 DOI: 10.1016/j.jmoldx.2024.08.011

Geert A Martens, Jan Demol, Franceska Dedeurwaerdere, Kristof De Smet, Janusz Wesolowski, Dieter De Smet

{"title":"Surveillance of Disease Progression in Metastatic Breast Cancer by Molecular Counting of Circulating Tumor DNA Using Plasma-SeqSensei Breast Cancer in Vitro Diagnostics Assay.","authors":"Geert A Martens, Jan Demol, Franceska Dedeurwaerdere, Kristof De Smet, Janusz Wesolowski, Dieter De Smet","doi":"10.1016/j.jmoldx.2024.08.011","DOIUrl":"10.1016/j.jmoldx.2024.08.011","url":null,"abstract":"Circulating tumor DNA (ctDNA) quantification surpasses cancer antigen 15 to 3 for metastatic breast cancer surveillance. Clinical translation, however, is limited because of uncertainties about the optimal method and clinically valid ctDNA decision thresholds. Plasma-SeqSensei Breast Cancer IVD kit (PSS) is a novel assay for ctDNA molecular counting, detecting ≥0.06% variant allele fractions in AKT1, ERBB2, ESR1, KRAS, PIK3CA, and TP53. PSS was validated against droplet digital PCR (ddPCR) in 201 samples from 16 subjects with PIK3CA/TP53-mutated cancers, longitudinally sampled for a median of 93 (range, 18 to 113) weeks, three to five weekly. PSS and ddPCR ctDNA levels correlate significantly (Spearman ρ, 0.923; 95% CI, 0.898-0.941) across 0% to 43% variant allele frequency (VAF) range. PSS predicts 12-week progression with high clinical accuracy (area under the curve, 0.848; 95% CI, 0.790-0.894). PSS validates a previously developed ddPCR classifier: <10 copies/mL (0.25% VAF); excludes >100 copies/mL (2.5% VAF); and confirms progression, with negative predictive value (95% CI) of 83% (76%-88%) and positive predictive value (95% CI) of 91% (81%-96%) (weighted κ, 0.856; 95% CI, 0.797-0.915). PSS thus confirms robust clinical thresholds (10 to 100 copies/mL, 0.25% to 2.5% VAF) for metastatic breast cancer surveillance, using absolute molecular counting.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":"25-35"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631504","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

SARCP, a Clinical Next-Generation Sequencing Assay for the Detection of Gene Fusions in Sarcomas: A Description of the First 652 Cases. SARCP，用于检测肉瘤基因融合的临床新一代测序测定：首批 652 例病例的描述。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-01-01 Epub Date: 2024-11-07 DOI: 10.1016/j.jmoldx.2024.10.004

Mazen A Atiq, Jagadheshwar Balan, Patrick R Blackburn, John M Gross, Jesse S Voss, Long Jin, Numrah Fadra, Jaime I Davila, Beth A Pitel, Simone Barreto Siqueira Parrilha Terra, Kay T Minn, Rory A Jackson, Christopher D Hofich, Kurt S Willkomm, Brenda J Peterson, Sydney N Clausen, Kandelaria M Rumilla, Sounak Gupta, Ying-Chun Lo, Cris M Ida, Jeremy F Molligan, Judith Jebastin Thangaiah, Matthew J Petersen, William R Sukov, Ruifeng Guo, Caterina Giannini, J Kenneth Schoolmeester, Karen Fritchie, Carrie Y Inwards, Andrew L Folpe, Andre M Oliveira, Jorge Torres-Mora, Benjamin R Kipp, Kevin C Halling

{"title":"SARCP, a Clinical Next-Generation Sequencing Assay for the Detection of Gene Fusions in Sarcomas: A Description of the First 652 Cases.","authors":"Mazen A Atiq, Jagadheshwar Balan, Patrick R Blackburn, John M Gross, Jesse S Voss, Long Jin, Numrah Fadra, Jaime I Davila, Beth A Pitel, Simone Barreto Siqueira Parrilha Terra, Kay T Minn, Rory A Jackson, Christopher D Hofich, Kurt S Willkomm, Brenda J Peterson, Sydney N Clausen, Kandelaria M Rumilla, Sounak Gupta, Ying-Chun Lo, Cris M Ida, Jeremy F Molligan, Judith Jebastin Thangaiah, Matthew J Petersen, William R Sukov, Ruifeng Guo, Caterina Giannini, J Kenneth Schoolmeester, Karen Fritchie, Carrie Y Inwards, Andrew L Folpe, Andre M Oliveira, Jorge Torres-Mora, Benjamin R Kipp, Kevin C Halling","doi":"10.1016/j.jmoldx.2024.10.004","DOIUrl":"10.1016/j.jmoldx.2024.10.004","url":null,"abstract":"An amplicon-based targeted next-generation sequencing (NGS) assay for the detection of gene fusions in sarcomas was developed, validated, and implemented. This assay can detect fusions in targeted regions of 138 genes and BCOR internal tandem duplications. This study reviews our experience with testing on the first 652 patients analyzed. Gene fusions were detected in 238 (36.5%) of 652 cases, including 83 distinct fusions in the 238 fusion-positive cases, 10 of which had not been previously described. Among the 238 fusion-positive cases, the results assisted in establishing a diagnosis for 137 (58%) cases, confirmed a suspected diagnosis in 66 (28%) cases, changed a suspected diagnosis in 25 (10%) cases, and were novel fusions with unknown clinical significance in 10 (4%) cases. Twenty-six cases had gene fusions (ALK, ROS1, NTRK1, NTRK3, and COL1A1::PDGFB) for which there are targetable therapies. BCOR internal tandem duplications were identified in 6 (1.2%) of 485 patients. Among the 138 genes in the panel, 66 were involved in one or more fusions, and 72 were not involved in any fusions. There was little overlap between the genes involved as 5'-partners (31 different genes) and 3'-partners (37 different genes). This study shows the clinical utility of a next-generation sequencing gene fusion detection assay for the diagnosis and treatment of sarcomas.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":"74-95"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631501","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

Development of a Body of Knowledge for the Clinical Bioinformatician: Perspectives from the Association for Molecular Pathology's Clinical Genomics Bioinformatician Body of Knowledge Steering Committee.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-12-27 DOI: 10.1016/j.jmoldx.2024.12.002

Somak Roy, Amber Fussell, Danielle Jordan, Sabah Kadri, Annette Leon, Ryan J Schmidt, Robyn L Temple-Smolkin, Jason D Merker

{"title":"Development of a Body of Knowledge for the Clinical Bioinformatician: Perspectives from the Association for Molecular Pathology's Clinical Genomics Bioinformatician Body of Knowledge Steering Committee.","authors":"Somak Roy, Amber Fussell, Danielle Jordan, Sabah Kadri, Annette Leon, Ryan J Schmidt, Robyn L Temple-Smolkin, Jason D Merker","doi":"10.1016/j.jmoldx.2024.12.002","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2024.12.002","url":null,"abstract":"The use of next-generation sequencing (NGS) and other high-throughput technologies in the clinical molecular diagnostics laboratory requires the application of bioinformatics pipelines and other computational tools to analyze, visualize, and store these clinical data. Clinical Bioinformaticians, individuals with the skills to develop, validate, and deploy these tools in a clinical setting, are needed to ensure that these molecular diagnostic technologies can be appropriately used for clinical care. Building on existing expertise in informatics, NGS, and clinical molecular diagnostics, the Association for Molecular Pathology (AMP) has generated a series to establish an initial Clinical Bioinformatician Body of Knowledge. These manuscripts cover the potential roles of the Clinical Bioinformatician, assist molecular laboratory and clinical bioinformatics directors in understanding the various roles of the clinical bioinformatics team members, and provide guidance regarding the competencies and skill sets required. The three manuscripts within this Body of Knowledge cover the following knowledge cores: (1) Molecular Diagnostics, (2) Clinical Bioinformatics, Software, and Database Knowledge, and (3) Clinical Laboratory Regulation and Data Security. Many of the topics covered in these manuscripts are broad and rapidly evolving; therefore, this AMP Clinical Bioinformatician Body of Knowledge manuscript series is designed to provide an initial framework for the core bioinformatics skills required to function successfully within a molecular diagnostic laboratory.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903590","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

Predicting Consanguinity Rates from Exome Sequencing Data in the Lebanese Population.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-12-24 DOI: 10.1016/j.jmoldx.2024.11.008

Eileen Marie Hanna, Cybel Mehawej, Joelle Assy, Sandra Corbani, Rima Korban, Andre Megarbane, Eliane Chouery

{"title":"Predicting Consanguinity Rates from Exome Sequencing Data in the Lebanese Population.","authors":"Eileen Marie Hanna, Cybel Mehawej, Joelle Assy, Sandra Corbani, Rima Korban, Andre Megarbane, Eliane Chouery","doi":"10.1016/j.jmoldx.2024.11.008","DOIUrl":"10.1016/j.jmoldx.2024.11.008","url":null,"abstract":"Consanguinity, prevalent in certain populations because of cultural and social factors, significantly increases the risk of genetic autosomal recessive disorders. In Lebanon, consanguineous marriages constitute 35.5% of unions, with first cousin marriages being the most common. This study aims to develop a model to predict consanguinity status using total runs of homozygosity (ROH) size derived from exome sequencing data. In this study, a cohort of 784 Lebanese individuals was analyzed, with consanguinity labels assigned based on pedigree information. ROHs were detected from exome sequencing data using AutoMap. The analysis focused on 521 subjects for whom the consanguinity or nonconsanguinity label was clearly determined, leading to the development of two logistic regression models: one including outliers (accuracy, 91%) and one excluding them (accuracy, 94%). The second model established specific ROH thresholds for categorizing consanguinity: nonconsanguineous [<40.28 megabases (Mb)], uncertain (40.28 to 79.17 Mb), probable consanguinity (79.17 to 118.06 Mb), and consanguineous (>118.06 Mb). This study provides a valuable tool for clinical genetics in populations with high consanguinity rates, offering insights into the genetic risks associated with consanguinity and aiding in the identification and counseling of affected individuals. Moreover, the current findings underline the importance of population-specific thresholds in accurately assessing consanguinity status.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900027","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

Development and Validation of a Rapid Point-of-Care CYP2C19 Genotyping Platform.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-12-24 DOI: 10.1016/j.jmoldx.2024.12.001

Kerry A Burke, James O'Sullivan, Nicola Godfrey, Videha Sharma, Sian Hilton, Stuart J Wright, Nicholas S Greaves, William G Newman, John H McDermott

{"title":"Development and Validation of a Rapid Point-of-Care CYP2C19 Genotyping Platform.","authors":"Kerry A Burke, James O'Sullivan, Nicola Godfrey, Videha Sharma, Sian Hilton, Stuart J Wright, Nicholas S Greaves, William G Newman, John H McDermott","doi":"10.1016/j.jmoldx.2024.12.001","DOIUrl":"10.1016/j.jmoldx.2024.12.001","url":null,"abstract":"Pharmacogenetic-guided prescribing can lead to more accurate medicine selection and dosing, improving patient outcomes and leading to better use of health care budgets. Loss-of-function variants in CYP2C19 influence an individual's ability to metabolize clopidogrel, increasing the risk of secondary vascular events following ischemic stroke and percutaneous coronary intervention. In acute clinical contexts, centralized laboratory-based testing is too slow to inform timely clinical decision-making. This work reports the development and analytical validation of the Genedrive CYP2C19 ID Kit, which provides rapid point-of-care genotyping from a buccal swab in approximately 1 hour. Buccal samples were collected from a total of 204 individuals between September 2023 and July 2024, alongside a blood or saliva sample for comparison with laboratory testing. In the final cohort of 202 patients, all point-of-care results were concordant with laboratory testing. In this assessment, the sensitivity and specificity of the CYP2C19 ID Kit was 100% (95% CI, 95.0%-100%) and 100% (95% CI, 97.2%-100%), respectively. The failure rate of the CYP2C19 ID Kit was 0.98%. This study confirms the analytical validity of the Genedrive CYP2C19 ID Kit. The Genedrive system is able to provide an accurate, rapid, noninvasive alternative to standard laboratory testing and can be used as a point-of-care test in the clinical environment.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900024","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