Journal of Molecular Diagnostics最新文献_第4页

Optimization of Tumor Dissection Procedures Leads to Measurable Improvement in the Quality of Molecular Testing 优化肿瘤解剖程序可显著提高分子检测的质量。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-25 DOI: 10.1016/j.jmoldx.2024.06.009

Bryan L. Betz , Corey S. Post , Jennifer Bergendahl , Nanci Lefebvre , Helmut Weigelin , Noah A. Brown

{"title":"Optimization of Tumor Dissection Procedures Leads to Measurable Improvement in the Quality of Molecular Testing","authors":"Bryan L. Betz , Corey S. Post , Jennifer Bergendahl , Nanci Lefebvre , Helmut Weigelin , Noah A. Brown","doi":"10.1016/j.jmoldx.2024.06.009","DOIUrl":"10.1016/j.jmoldx.2024.06.009","url":null,"abstract":"<div><p>Molecular tests have an inherent limit of detection (LOD) and, therefore, require samples with sufficiently high percentages of neoplastic cells. Many laboratories use tissue dissection; however, optimal procedures for dissection and quality assurance measures have not been established. In this study, several modifications to tissue dissection procedures and workflow were introduced over 4 years. Each modification resulted in a significant improvement in one or more quality assurance measures. The review of materials following dissection resulted in a 90% reduction in <em>KRAS</em> mutations below the stated LOD (<em>P</em> = 0.004). Mutation allele frequencies correlated best with estimated tumor percentages for pathologists with more experience in this process. The direct marking of unstained slides, use of a stereomicroscope, validation of extraction from diagnostic slides, and use of a robust, targeted next-generation sequencing platform all resulted in reduction of quantity not sufficient specimens from 20% to 25% to nearly 0%, without a significant increase in test failures or mutations below the LOD. These data indicate that post-dissection review of unstained slides and monitoring quantity not sufficient rate, test failure rate, and mutation allele frequencies are important tumor dissection quality assurance measures that should be considered by laboratories performing tissue dissections. The amendments to tissue dissection procedures enacted during this study resulted in a measurable improvement in the quality and reliability of this process based on these metrics.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001624/pdfft?md5=7ea2902809fe522e8be547b057d149fb&pid=1-s2.0-S1525157824001624-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789708","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

A Network-Based Framework to Discover Treatment-Response–Predicting Biomarkers for Complex Diseases 发现复杂疾病治疗反应预测生物标志物的网络框架。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-25 DOI: 10.1016/j.jmoldx.2024.06.008

Uday S. Shanthamallu , Casey Kilpatrick , Alex Jones , Jonathan Rubin , Alif Saleh , Albert-László Barabási , Viatcheslav R. Akmaev , Susan D. Ghiassian

{"title":"A Network-Based Framework to Discover Treatment-Response–Predicting Biomarkers for Complex Diseases","authors":"Uday S. Shanthamallu , Casey Kilpatrick , Alex Jones , Jonathan Rubin , Alif Saleh , Albert-László Barabási , Viatcheslav R. Akmaev , Susan D. Ghiassian","doi":"10.1016/j.jmoldx.2024.06.008","DOIUrl":"10.1016/j.jmoldx.2024.06.008","url":null,"abstract":"<div><p>The potential of precision medicine to transform complex autoimmune disease treatment is often challenged by limited data availability and inadequate sample size when compared with the number of molecular features found in high-throughput multi-omics data sets. To address this issue, the novel framework PRoBeNet (Predictive Response Biomarkers using Network medicine) was developed. PRoBeNet operates under the hypothesis that the therapeutic effect of a drug propagates through a protein-protein interaction network to reverse disease states. PRoBeNet prioritizes biomarkers by considering i) therapy-targeted proteins, ii) disease-specific molecular signatures, and iii) an underlying network of interactions among cellular components (the human interactome). PRoBeNet helped discover biomarkers predicting patient responses to both an established autoimmune therapy (infliximab) and an investigational compound (a mitogen-activated protein kinase 3/1 inhibitor). The predictive power of PRoBeNet biomarkers was validated with retrospective gene-expression data from patients with ulcerative colitis and rheumatoid arthritis and prospective data from tissues from patients with ulcerative colitis and Crohn disease. Machine-learning models using PRoBeNet biomarkers significantly outperformed models using either all genes or randomly selected genes, especially when data were limited. These results illustrate the value of PRoBeNet in reducing features and for constructing robust machine-learning models when data are limited. PRoBeNet may be used to develop companion and complementary diagnostic assays, which may help stratify suitable patient subgroups in clinical trials and improve patient outcomes.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001612/pdfft?md5=3259c4090584f8080a3f5dff87b12860&pid=1-s2.0-S1525157824001612-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789706","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

Genotype and Phenotype Correlation of Patients with Osteogenesis Imperfecta 成骨不全症患者基因型与表型的相关性

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-20 DOI: 10.1016/j.jmoldx.2024.05.014

Lamiya Aliyeva , Yasemin Denkboy Ongen , Erdal Eren , Mehmet B. Sarisozen , Adem Alemdar , Sehime G. Temel , Sebnem Ozemri Sag

{"title":"Genotype and Phenotype Correlation of Patients with Osteogenesis Imperfecta","authors":"Lamiya Aliyeva , Yasemin Denkboy Ongen , Erdal Eren , Mehmet B. Sarisozen , Adem Alemdar , Sehime G. Temel , Sebnem Ozemri Sag","doi":"10.1016/j.jmoldx.2024.05.014","DOIUrl":"10.1016/j.jmoldx.2024.05.014","url":null,"abstract":"<div><p>Osteogenesis imperfecta (OI) is the most common inherited connective tissue disease of the bone, characterized by recurrent fractures and deformities. In patients displaying the OI phenotype, genotype–phenotype correlation is used to screen multiple genes swiftly, identify new variants, and distinguish between differential diagnoses and mild subtypes. This study evaluated variants identified through next-generation sequencing in 58 patients with clinical characteristics indicative of OI. The cohort included 18 adults, 37 children, and 3 fetuses. Clinical classification revealed 25 patients as OI type I, three patients as OI type II, 18 as OI type III, and 10 as OI type IV. Fifteen variants in <em>COL1A1</em> were detected in 19 patients, 9 variants in <em>COL1A2</em> (<em>n</em> = 19), 5 variants in <em>LEPRE1/P3H1</em> (<em>n</em> = 7), 3 variants in <em>FKBP10</em> (<em>n</em> = 4), 3 variants in <em>SERPINH1</em> (<em>n</em> = 2), 1 variant in <em>IFITM5</em> (<em>n</em> = 1), and 1 variant in <em>PLS3</em> (<em>n</em> = 1). In total, 37 variants (18 pathogenic, 14 likely pathogenic, and 5 variants of uncertain significance), including 16 novel variants, were identified in 43 (37 probands, 6 family members) of the 58 patients analyzed. This study highlights the efficacy of panel testing in the molecular diagnosis of OI, the significance of the next-generation sequencing technique, and the importance of genotype–phenotype correlation.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724945","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

Strategic Implementation of Fragile X Carrier Screening in China 中国脆性 X 携带者筛查的战略实施：重点试点研究。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-19 DOI: 10.1016/j.jmoldx.2024.06.005

Jin Xue , Yingbao Zhu , Yi Pan , Hongjing Huang , Liyi Wei , Ying Peng , Hui Xi , Shihao Zhou , Hongliang Wu , Zhenxiang Gu , Wen Huang , Hua Wang , Ranhui Duan

{"title":"Strategic Implementation of Fragile X Carrier Screening in China","authors":"Jin Xue , Yingbao Zhu , Yi Pan , Hongjing Huang , Liyi Wei , Ying Peng , Hui Xi , Shihao Zhou , Hongliang Wu , Zhenxiang Gu , Wen Huang , Hua Wang , Ranhui Duan","doi":"10.1016/j.jmoldx.2024.06.005","DOIUrl":"10.1016/j.jmoldx.2024.06.005","url":null,"abstract":"<div><p>Fragile X syndrome is the leading genetic cause of intellectual disability and autism spectrum disorders. Female premutation carriers exhibit no obvious symptoms during reproductive age, but the premutation allele can expand to full mutation when transmitted to the fetus. Given the relatively low prevalence but large population, the distinct health care system, the middle-income economic status, and low awareness among public and medical professionals, the optimal genetic screening strategy remains unknown. We conducted a pilot study of Fragile X carrier screening in China, involving 22,245 pregnant women and women with childbearing intentions, divided into control and pilot groups. The prevalence of Fragile X carriers in the control group was 1 of 850, similar to East Asian populations. Strikingly, the prevalence of Fragile X carriers in the pilot group was 1 of 356, which can be attributed to extensive medical training, participant education, and rigorous genetic counseling and testing protocols. Cost-effectiveness analyses of four strategies—no screening, population-based screening, targeted screening, and our pilot screening—indicated that our pilot screening was the most cost-effective option. A follow-up survey revealed that 55% of respondents reported undergoing screening because of their family history. We have successfully established a standardized system, addressing the challenges of low prevalence, limited awareness, and genetic testing complexities. Our study provides practical recommendations for implementing Fragile X carrier screening in China.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735542","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

DPYD Genotyping Recommendations DPYD 基因分型建议：分子病理学协会、美国医学遗传学和基因组学学院、临床药物遗传学实施联合会、美国病理学家学会、荷兰皇家药剂师协会荷兰药物遗传学工作组、欧洲药物基因组学和个性化治疗学会、药物基因组学知识库和药物基因变异联合会的联合共识建议。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-18 DOI: 10.1016/j.jmoldx.2024.05.015

Victoria M. Pratt , Larisa H. Cavallari , Makenzie L. Fulmer , Andrea Gaedigk , Houda Hachad , Yuan Ji , Lisa V. Kalman , Reynold C. Ly , Ann M. Moyer , Stuart A. Scott , Amy J. Turner , Ron H.N. van Schaik , Michelle Whirl-Carrillo , Karen E. Weck

{"title":"DPYD Genotyping Recommendations","authors":"Victoria M. Pratt , Larisa H. Cavallari , Makenzie L. Fulmer , Andrea Gaedigk , Houda Hachad , Yuan Ji , Lisa V. Kalman , Reynold C. Ly , Ann M. Moyer , Stuart A. Scott , Amy J. Turner , Ron H.N. van Schaik , Michelle Whirl-Carrillo , Karen E. Weck","doi":"10.1016/j.jmoldx.2024.05.015","DOIUrl":"10.1016/j.jmoldx.2024.05.015","url":null,"abstract":"<div><p>The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations for a minimum set of variant alleles (tier 1) and an extended list of variant alleles (tier 2) that will aid clinical laboratories when designing assays for PGx testing. The Association for Molecular Pathology PGx Working Group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. The goal of this Working Group is to promote standardization of PGx testing across clinical laboratories. This document will focus on clinical <em>DPYD</em> PGx testing that may be applied to all dihydropyrimidine dehydrogenase–related medications. These recommendations are not to be interpreted as prescriptive but to provide a reference guide.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001545/pdfft?md5=e0bda1c43cd5d77f5cf6e9737bd1ec28&pid=1-s2.0-S1525157824001545-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735540","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

Multisite Evaluation and Validation of Optical Genome Mapping for Prenatal Genetic Testing 用于产前基因检测的光学基因组图谱的多点评估和验证。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-18 DOI: 10.1016/j.jmoldx.2024.06.006

Brynn Levy , Jie Liu , M. Anwar Iqbal , Barbara DuPont , Nikhil Sahajpal , Monique Ho , Jingwei Yu , Sam J. Brody , Mythily Ganapathi , Aleksandar Rajkovic , Teresa A. Smolarek , Fatih Boyar , Peter Bui , Adrian M. Dubuc , Ravindra Kolhe , Roger E. Stevenson

{"title":"Multisite Evaluation and Validation of Optical Genome Mapping for Prenatal Genetic Testing","authors":"Brynn Levy , Jie Liu , M. Anwar Iqbal , Barbara DuPont , Nikhil Sahajpal , Monique Ho , Jingwei Yu , Sam J. Brody , Mythily Ganapathi , Aleksandar Rajkovic , Teresa A. Smolarek , Fatih Boyar , Peter Bui , Adrian M. Dubuc , Ravindra Kolhe , Roger E. Stevenson","doi":"10.1016/j.jmoldx.2024.06.006","DOIUrl":"10.1016/j.jmoldx.2024.06.006","url":null,"abstract":"<div><p>Prenatal diagnostic testing of amniotic fluid, chorionic villi, or more rarely, fetal cord blood is recommended following a positive or unreportable noninvasive cell-free fetal DNA test, abnormal maternal biochemical serum screen, abnormal ultrasound, or increased genetic risk for a cytogenomic abnormality based on family history. Although chromosomal microarray is recommended as the first-tier prenatal diagnostic test, in practice, multiple assays are often assessed in concert to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping (OGM) is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenomic aberrations. In an effort to characterize the potential of OGM as a novel alternative to traditional standard of care (SOC) testing of prenatal samples, OGM was performed on a total of 200 samples representing 123 unique cases, which were previously tested with SOC methods (92/123 = 74.7% cases tested with at least two SOCs). OGM demonstrated an overall accuracy of 99.6% when compared with SOC methods, a positive predictive value of 100%, and 100% reproducibility between sites, operators, and instruments. The standardized workflow, cost-effectiveness, and high-resolution cytogenomic analysis demonstrate the potential of OGM to serve as a first-tier test for prenatal diagnosis.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001570/pdfft?md5=5bf6d88f32dd52ed0a19de6229f626d7&pid=1-s2.0-S1525157824001570-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735541","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

Characterization of Reference Materials for DPYD DPYD 参考材料的表征：GeT-RM 合作项目。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-18 DOI: 10.1016/j.jmoldx.2024.06.004

Andrea Gaedigk , Amy J. Turner , Ann M. Moyer , Pablo Zubiaur , Erin C. Boone , Wendy Y. Wang , Ulrich Broeckel , Lisa V. Kalman

{"title":"Characterization of Reference Materials for DPYD","authors":"Andrea Gaedigk , Amy J. Turner , Ann M. Moyer , Pablo Zubiaur , Erin C. Boone , Wendy Y. Wang , Ulrich Broeckel , Lisa V. Kalman","doi":"10.1016/j.jmoldx.2024.06.004","DOIUrl":"10.1016/j.jmoldx.2024.06.004","url":null,"abstract":"<div><p>The <em>DPYD</em> gene encodes dihydropyrimidine dehydrogenase (DPD), which is involved in the catalysis of uracil and thymine, as well as 5-fluorouracil (5-FU), which is used to treat solid tumors. Patients with decreased DPD activity are at risk of serious, sometimes fatal, adverse drug reactions to this important cancer drug. Pharmacogenetic testing for <em>DPYD</em> is increasingly provided by clinical and research laboratories; however, only a limited number of quality control and reference materials are currently available for clinical <em>DPYD</em> testing. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention–based Genetic Testing Reference Materials Coordination Program, in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 33 DNA samples derived from Coriell cell lines for <em>DPYD</em>. Samples were distributed to four volunteer laboratories for genetic testing using a variety of commercially available and laboratory-developed tests. Sanger sequencing was used by one laboratory and publicly available whole-genome sequence data from the 1000 Genomes Project were used by another to inform genotype. Thirty-three distinct <em>DPYD</em> variants were identified among the 33 samples characterized. These publicly available and well-characterized materials can be used to support the quality assurance and quality control programs of clinical laboratories performing clinical pharmacogenetic testing.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735539","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 and Implementation of a Somatic-Only Tumor Exome for Routine Clinical Application 用于常规临床应用的体细胞肿瘤外显子组的验证和实施。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-06 DOI: 10.1016/j.jmoldx.2024.05.013

引用次数: 0

The Utility of Real-Time PCR, Metagenomic Next-Generation Sequencing, and Culture in Bronchoalveolar Lavage Fluid for Diagnosis of Pulmonary Aspergillosis 实时 PCR、元基因组新一代测序和支气管肺泡灌洗液培养在诊断肺曲霉菌病中的实用性。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-06 DOI: 10.1016/j.jmoldx.2024.06.003

{"title":"The Utility of Real-Time PCR, Metagenomic Next-Generation Sequencing, and Culture in Bronchoalveolar Lavage Fluid for Diagnosis of Pulmonary Aspergillosis","authors":"","doi":"10.1016/j.jmoldx.2024.06.003","DOIUrl":"10.1016/j.jmoldx.2024.06.003","url":null,"abstract":"<div><p>Timely detection of <em>Aspergillus</em> infection is crucial given the high mortality rate of pulmonary aspergillosis (PA). Here, the diagnostic performances for PA of mycological culture, <em>Aspergillus</em> real-time PCR, and metagenomic next-generation sequencing (mNGS) assay from bronchoalveolar lavage fluid, were evaluated. In total, 139 patients with suspected fungal pneumonia were enrolled between December 2021 and July 2023, collecting 139 bronchoalveolar lavage fluid samples for real-time PCR and culture, with 87 undergoing mNGS assay. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve with 95% CIs of these assays for PA were as follows: 35.3% (14.2%–61.7%), 100.0% (94.0%–100.0%), 100.0% (54.1%–100.0%), 84.5% (79.3%–88.6%), and 0.676 (0.560–0.779), respectively, for culture; 82.4% (56.6%–96.2%), 98.3% (91.1%–100.0%), 93.3% (66.4%–99.0%), 95.2% (87.6%–98.2%), and 0.903 (0.815–0.959), respectively, for same diagnostic performance of real-time PCR and mNGS; and 94.1% (71.3%–99.9%), 96.7% (88.5%–99.6%), 88.9% (67.1%–96.9%), 98.3% (89.6%–99.7%), and 0.954 (0.880–0.989), respectively, for real-time PCR combining mNGS; real-time PCR, mNGS, and their combination significantly improved in area under the curve values over culture (<em>P</em> < 0.001), but real-time PCR testing and mNGS had no significant difference with each other and their combination. Overall, the performance of culture was limited by low sensitivity; both real-time PCR and mNGS assays as single diagnostic tests are promising compared with culture and combined tests.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555829","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

Assessing the Risk Stratification of Breast Cancer Polygenic Risk Scores in a Brazilian Cohort 评估巴西队列中乳腺癌多基因风险评分的风险分层。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-07-06 DOI: 10.1016/j.jmoldx.2024.06.002

{"title":"Assessing the Risk Stratification of Breast Cancer Polygenic Risk Scores in a Brazilian Cohort","authors":"","doi":"10.1016/j.jmoldx.2024.06.002","DOIUrl":"10.1016/j.jmoldx.2024.06.002","url":null,"abstract":"<div><p>Polygenic risk scores (PRSs) for breast cancer have a clear clinical utility in risk prediction. PRS transferability across populations and ancestry groups is hampered by population-specific factors, ultimately leading to differences in variant effects, such as linkage disequilibrium and differences in variant frequency (allele frequency differences). Thus, locally sourced population-based phenotypic and genomic data sets are essential to assess the validity of PRSs derived from signals detected across populations. This study assesses the transferability of a breast cancer PRS composed of 313 risk variants (313-PRS) in a Brazilian trihybrid admixed ancestries (European, African, and Native American) whole-genome sequenced cohort, the Rare Genomes Project. 313-PRS was computed in the Rare Genomes Project (<em>n</em> = 853) using the UK Biobank (UKBB; <em>n</em> = 264,307) as reference. The Brazilian cohorts have a high European ancestry (EA) component, with allele frequency differences and to a lesser extent linkage disequilibrium patterns similar to those found in EA populations. The 313-PRS distribution was found to be inflated when compared with that of the UKBB, leading to potential overestimation of PRS-based risk if EA is taken as a standard. However, case controls lead to equivalent predictive power when compared with UKBB-EA samples with area under the receiver operating characteristic curve values of 0.66 to 0.62 compared with 0.63 for UKBB.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555827","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