Clinical chemistry and laboratory medicine最新文献

{"title":"Generative artificial intelligence (AI) for reporting the performance of laboratory biomarkers: not ready for prime time.","authors":"Laura Pighi, Davide Negrini, Giuseppe Lippi","doi":"10.1515/cclm-2024-0857","DOIUrl":"https://doi.org/10.1515/cclm-2024-0857","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An ultrasensitive DNA-enhanced amplification method for detecting cfDNA drug-resistant mutations in non-small cell lung cancer with selective FEN-assisted degradation of dominant somatic fragments","authors":"Junhua Zhang, Yifei Li, Wei Huang, Gaoyuan Sun, Hongjun Ren, Min Tang","doi":"10.1515/cclm-2024-0614","DOIUrl":"https://doi.org/10.1515/cclm-2024-0614","url":null,"abstract":"Objectives Blood cell-free DNA (cfDNA) can be a new reliable tool for detecting epidermal growth factor receptor (<jats:italic>EGFR</jats:italic>) mutations in non-small cell lung cancer (NSCLC) patients. However, the currently reported cfDNA assays have a limited role in detecting drug-resistant mutations due to their deficiencies in sensitivity, stability, or mutation detection rate. Methods We developed an <jats:italic>Archaeoglobus fulgidus</jats:italic>-derived flap endonuclease (<jats:italic>Afu</jats:italic> FEN)-based DNA-enhanced amplification system of mutated cfDNA by designing a pair of hairpin probes to anneal with wild-type cfDNA to form two 5′-flaps, allowing for the specific cleavage of wild-type cfDNA by <jats:italic>Afu</jats:italic> FEN. When the dominant wild-type somatic cfDNA fragments were cleaved by structure-recognition-specific <jats:italic>Afu</jats:italic> FEN, the proportion of mutated cfDNA in the reaction system was greatly enriched. As the amount of mutated cfDNA in the system was further increased by PCR amplification, the mutation status could be easily detected through first-generation sequencing. Results In a mixture of synthetic wild-type and T790M <jats:italic>EGFR</jats:italic> DNA fragments, our new assay still could detect T790M mutation at the fg level with remarkably high sensitivity. We also tested its performance in detecting low variant allele frequency (VAF) mutations in clinical samples from NSCLC patients. The plasma cfDNA samples with low VAF (0.1 and 0.5 %) could be easily detected by DNA-enhanced amplification. Conclusions This system with enhanced amplification of mutated cfDNA is an effective tool used for the early screening and individualized targeted therapy of NSCLC by providing a rapid, sensitive, and economical way for the detection of drug-resistant mutations in tumors.","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of serum CC16 by a rapid and ultrasensitive magnetic chemiluminescence immunoassay for lung disease diagnosis.","authors":"Kaili Duan, Yu Xiang, Yilong Deng, Junman Chen, Ping Liu","doi":"10.1515/cclm-2024-0724","DOIUrl":"https://doi.org/10.1515/cclm-2024-0724","url":null,"abstract":"<p><strong>Objectives: </strong>It has been reported that serum Clara cell secreted protein 16 (CC16) is a potential biomarker for lung injury diseases, but currently, there is no other method that is faster, more accurate, or more sensitive being applied in clinical practice apart from ELISA. The current study was designed to established a magnetic nanoparticles chemiluminescence immunoassay (MNPs-CLIA) for highly sensitive automated detection of serum Clara cell secretory protein 16 (CC16), and validated its diagnostic performance for lung disease.</p><p><strong>Methods: </strong>The study included the expression of CC16 recombinant protein, the preparation and screening of its monoclonal antibody (MAb), as well as the construction, optimization and analytical evaluation of the MNPs-CLIA method. The clinical application value of this method was investigated by detecting CC16 level in 296 serum samples.</p><p><strong>Results: </strong>The linear range of the MNPs-CLIA assay system was 0.2-50 ng/mL, and the limit of detection was 0.037 ng/mL. Performance parameters such as specificity, recovery rate, and precision can meet the industry standards of <i>in vitro</i> diagnostic reagents. The established method reveals consistent results with ELISA (R²=0.9962) currently used clinically, and it also exhibits satisfactory diagnostic efficacy of silicosis, chronic obstructive pulmonary disease (COPD), and pulmonary sarcoidosis, with areas under the curve (AUC) of 0.9748, 0.8428 and 0.9128, respectively.</p><p><strong>Conclusions: </strong>Our established MNPs-CLIA method has the advantages of automation, high throughput, rapidity, and simplicity, and can be promoted for widely popularized in clinical applications. MNPs-CLIA detection of serum CC16 has efficient diagnostic potentiality for predicting and diagnosing lung diseases.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate non-ceruloplasmin bound copper: a new biomarker for the assessment and monitoring of Wilson disease patients using HPLC coupled to ICP-MS/MS.","authors":"Chris F Harrington, Geoff Carpenter, James P C Coverdale, Leisa Douglas, Craig Mills, Karl Willis, Michael L Schilsky","doi":"10.1515/cclm-2024-0213","DOIUrl":"https://doi.org/10.1515/cclm-2024-0213","url":null,"abstract":"<p><strong>Objectives: </strong>Assessment of Wilson disease is complicated, with neither ceruloplasmin, nor serum or urine copper, being reliable. Two new indices, accurate non-ceruloplasmin copper (ANCC) and relative ANCC were developed and applied to a cohort of 71 patients, as part of a Wilson Disease Registry Study.</p><p><strong>Methods: </strong>Elemental copper-protein speciation was developed for holo-ceruloplasmin quantitation using strong anion exchange chromatography coupled to triple quadrupole inductively coupled plasma mass spectrometry. The serum proteins were separated using gradient elution and measured at <i>m</i>/<i>z</i> 63 (⁶³Cu⁺) and 48 (³²S¹⁶O⁺) using oxygen reaction mode and Cu-EDTA as calibration standard. The ANCC was calculated by subtraction of the ceruloplasmin bound copper from the total serum copper and the RelANCC was the percentage of total copper present as the ANCC.</p><p><strong>Results: </strong>The accuracy of the holo-ceruloplasmin measurement was established using two certified reference materials, giving a mean recovery of 94.2 %. Regression analysis between the sum of the copper containing species and total copper concentration in the patient samples was acceptable (slope=0.964, intercept=0, r=0.987) and a difference plot, gave a mean difference for copper of 0.38 μmol/L. Intra-day precision for holo-ceruloplasmin at serum copper concentrations of 0.48 and 3.20 μmol/L were 5.2 and 5.6 % CV and the intermediate precision at concentrations of 0.80 and 5.99 μmol/L were 6.4 and 6.4 % CV, respectively. The limit of detection (LOD) and lower limit of quantification (LLOQ) for holo-ceruloplasmin were 0.08 and 0.27 μmol/L as copper, respectively.</p><p><strong>Conclusions: </strong>ANCC and Relative ANCC are important new diagnostic and monitoring biomarker indices for Wilson disease (WD).</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preservation of urine specimens for metabolic evaluation of recurrent urinary stone formers.","authors":"Tomáš Šálek, Pavel Musil, Pieter Vermeersch, Rachel Marrington, Zeliha G Dikmen, Radka Poláchová, Ulrike Kipman, Timo T Kouri, Janne Cadamuro","doi":"10.1515/cclm-2024-0773","DOIUrl":"https://doi.org/10.1515/cclm-2024-0773","url":null,"abstract":"<p><strong>Objectives: </strong>Stability of concentrations of urinary stone-related metabolites was analyzed from samples of recurrent urinary stone formers to assess necessity and effectiveness of urine acidification during collection and storage.</p><p><strong>Methods: </strong>First-morning urine was collected from 20 adult calcium-stone forming patients at Tomas Bata Hospital in the Czech Republic. Urine samples were analyzed for calcium, magnesium, inorganic phosphate, uric acid, sodium, potassium, chloride, citrate, oxalate, and urine particles. The single-voided specimens were collected without acidification, after which they were divided into three groups for storage: samples without acidification (\"NON\"), acidification before storage (\"PRE\"), or acidification after storage (\"POST\"). The analyses were conducted on the day of arrival (day 0, \"baseline\"), or after storage for 2 or 7 days at room temperature. The maximum permissible difference (<i>MPD</i>) was defined as ±20 % from the baseline.</p><p><strong>Results: </strong>The urine concentrations of all stone-related metabolites remained within the 20 % <i>MPD</i> limits in NON and POST samples after 2 days, except for calcium in NON sample of one patient, and oxalate of three patients and citrate of one patient in POST samples. In PRE samples, stability failed in urine samples for oxalate of three patients, and for uric acid of four patients after 2 days. Failures in stability often correlated with high baseline concentrations of those metabolites in urine.</p><p><strong>Conclusions: </strong>Detailed procedures are needed to collect urine specimens for analysis of urinary stone-related metabolites, considering both patient safety and stability of those metabolites. We recommend specific preservation steps.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing value-based laboratory medicine.","authors":"Mario Plebani","doi":"10.1515/cclm-2024-0823","DOIUrl":"10.1515/cclm-2024-0823","url":null,"abstract":"<p><p>Following the COVID-19 pandemic, the concepts of value-based medicine (VBM) and value-based laboratory medicine (VBLM) are receiving increasing interest to improve the quality, sustainability and safety of healthcare. Laboratory medicine is well positioned to support the transition to value-based healthcare as it helps to improve clinical outcomes and healthcare sustainability by reducing the time to diagnosis, improving diagnostic accuracy, providing effective guidance for tailored therapies and monitoring, and supporting screening and wellness care. However, the perception of the value of laboratory medicine is still limited, to the extent that it has been defined a \"profession without a face\", often lacking visibility to patients and the public. In addition, in recent decades, clinical laboratories have sought to improve the ration between outcomes and costs by increasing efficiency and reducing the cost per test rather than improving clinical outcomes. The aim of this paper is to propose a 10-point manifesto for implementing value-based laboratory medicine in clinical practice.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of biochemical algorithms to screen dysbetalipoproteinemia in ε2ε2 and rare APOE variants carriers","authors":"Louise Michenaud, Nathanaël Marrié, Antoine Rimbert, Oriane Marmontel, Sybil Charrière, Charles Gibert, Caroline Bouveyron, Jade Mammi, Bertrand Cariou, Philippe Moulin, Mathilde Di Filippo","doi":"10.1515/cclm-2024-0587","DOIUrl":"https://doi.org/10.1515/cclm-2024-0587","url":null,"abstract":"Objectives Dysbetalipoproteinemia (DBL) is a combined dyslipidemia associated with an increased risk of atherosclerotic cardiovascular diseases mostly occurring in ε2ε2 subjects and infrequently in subjects with rare <jats:italic>APOE</jats:italic> variants. Several algorithms have been proposed to screen DBL. In this work, we compared the diagnostic performances of nine algorithms including a new one. Methods Patients were divided into 3 groups according to their <jats:italic>APOE</jats:italic> genotype: ε2ε2 (“ε2ε2”, n=49), carriers of rare variants (“APOEmut”, n=20) and non-carriers of ε2ε2 nor <jats:italic>APOE</jats:italic> rare variant (“controls”, n=115). The algorithms compared were those from Fredrickson, Sniderman, Boot, Paquette, De Graaf, Sampson, eSampson, Bea and ours, the “Hospices Civils de Lyon (HCL) algorithm”. Our gold standard was the presence of a ε2ε2 genotype or of a rare variant associated with triglycerides (TG) &gt;1.7 mmol/L. A replication in the UK Biobank and a robustness analysis were performed by considering only subjects with both TG and low-density lipoprotein-cholesterol (LDLc) &gt;90th percentile. Results Total cholesterol (TC)/ApoB and NHDLC/ApoB are the best ratios to suspect DBL. In ε2ε2, according to their likelihood ratios (LR), the most clinically efficient algorithms were the HCL, Sniderman and De Graaf’s. In APOEmut, Sniderman’s algorithm exhibited the lowest negative LR (0.07) whereas the HCL’s exhibited the highest positive LR (29). In both cohorts, the HCL algorithm had the best LR. Conclusions We proposed a powerful algorithm based on ApoB concentration and the routine lipid profile, which performs remarkably well in detecting ε2ε2 or <jats:italic>APOE</jats:italic> variant-related DBL. Additional studies are needed to further evaluate algorithms performances in DBL carriers of infrequent <jats:italic>APOE</jats:italic> variants.","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of ELISA-comparable moderate and high thresholds for anticardiolipin and anti-β2 glycoprotein I chemiluminescent immunoassays according to the 2023 ACR/EULAR APS classification criteria and evaluation of their diagnostic performance.","authors":"Polona Žigon, Nika Boštic, Aleš Ambrožič, Žiga Rotar, Elizabeta Blokar, Manca Ogrič, Saša Čučnik","doi":"10.1515/cclm-2024-0570","DOIUrl":"https://doi.org/10.1515/cclm-2024-0570","url":null,"abstract":"<p><strong>Objectives: </strong>Recently published 2023 ACR/EULAR APS classification criteria emphasize the importance of quantifying single-, double-, and triple-antiphospholipid antibody positivity, distinguishing between IgG and IgM isotypes, and delineating moderate/high levels of anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies. We aimed to establish clinically important moderate/high thresholds for aCL and anti-β2GPI IgG/IgM chemiluminescent immunoassays (CLIA), in particular QUANTA Flash, comparable to our in-house ELISAs used for over two decades, and to evaluate their diagnostic performance.</p><p><strong>Methods: </strong>QUANTA Flash CLIA and in-house ELISAs were used to measure aCL and anti-β2GPI IgG/IgM. Moderate thresholds for QUANTA Flash CLIA were determined using a non-parametric approach, calculating a 99th percentile on serum samples from 139 blood donors, and by mirroring the diagnostic performance of in-house ELISA on 159 patient samples.</p><p><strong>Results: </strong>Thresholds for QUANTA Flash CLIA achieving diagnostic performance equivalent to in-house ELISAs were 40 CU for moderate and 80 CU for high levels for aCL and anti-β2GPI IgG and IgM. The assays showed good qualitative agreement, ranging from 76.10 to 91.19 %. When considering in-house ELISA results, 14 out of 80 (17.5 %) patients did not fulfill the new ACR/EULAR laboratory classification criteria, while 27 out of 80 (33.8 %) did not when considering QUANTA Flash CLIA results.</p><p><strong>Conclusions: </strong>We determined moderate and high thresholds for aCL and anti-β2GPI IgG and IgM detected with QUANTA Flash CLIA, aligning with long-established in-house ELISA thresholds. These thresholds are crucial for seamlessly integrating of the new 2023 ACR/EULAR classification criteria into future observational clinical studies and trials.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of monoclonal gammopathy and isoelectric focusing pattern 5 on the free light chain kappa diagnostics in cerebrospinal fluid.","authors":"Malte J Hannich, Franz F Konen, Konrad Gag, Aiham Alkhayer, Seda N Türker, Kathrin Budde, Matthias Nauck, Ulrich Wurster, Alexander Dressel, Thomas Skripuletz, Marie Süße","doi":"10.1515/cclm-2023-1468","DOIUrl":"https://doi.org/10.1515/cclm-2023-1468","url":null,"abstract":"<p><strong>Objectives: </strong>Oligoclonal bands (OCB) analysis is the reference standard for detecting an intrathecal IgG synthesis. Alongside OCB, free light chains kappa (FLCκ) are considered an additional sensitive biomarker for determining patterns 2 or 3, indicating intrathecal Ig synthesis. However, kFLC IF is not suitable for detecting a monoclonal pattern 5. The primary aim of this study was to evaluate the impact of incorporating FLCκ analysis into routine cerebrospinal fluid (CSF) diagnostics instead of OCB testing on the rate of missed monoclonal IgG detection.</p><p><strong>Methods: </strong>A two-center retrospective biomarker study was conducted. OCB were identified using isoelectric focusing in polyacrylamide gels followed by silver staining or in agarose gels followed by immunofixation. FLCκ were quantified using nephelometry and FLCκ assay (Siemens).</p><p><strong>Results: </strong>Out of a combined total of 17,755 OCB analyses conducted between 2011 and 2021, a subset of 269 cases (1.5 %) exhibited pattern 5. 98 samples (36 %), which included 18 samples with intrathecal inflammation as determined by additional OCB pattern 2 were included in the FLCκ analysis. Of those, 16 (89 %) had intrathecal FLCκ synthesis.</p><p><strong>Conclusions: </strong>While FLCκ offers a promising avenue for detecting an intrathecal inflammation, the pattern 5, though rare, remains a valuable additional finding of OCB analysis. A combined approach of FLCκ and OCB analysis is recommended for a comprehensive assessment of the humoral intrathecal immune response.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical utility of regions of homozygosity (ROH) identified in exome sequencing: when to pursue confirmatory uniparental disomy testing for imprinting disorders?","authors":"Xiaoyan Huo, Xinyi Lu, Deyun Lu, Huili Liu, Yi Liu, Qianfeng Zhao, Yu Sun, Weiqian Dai, Wenjuan Qiu, Yongguo Yu, Yanjie Fan","doi":"10.1515/cclm-2024-0239","DOIUrl":"https://doi.org/10.1515/cclm-2024-0239","url":null,"abstract":"<p><strong>Objectives: </strong>Regions of homozygosity (ROH) could implicate uniparental disomy (UPD) on specific chromosomes associated with imprinting disorders. Though the algorithms for ROH detection in exome sequencing (ES) have been developed, optimal reporting thresholds and when to pursue confirmatory UPD testing for imprinting disorders remain in ambiguity. This study used a data-driven approach to assess optimal reporting thresholds of ROH in clinical practice.</p><p><strong>Methods: </strong>ROH analysis was performed using Automap in a retrospective cohort of 8,219 patients and a prospective cohort of 1,964 patients with ES data. Cases with ROH on imprinting-disorders related chromosomes were selected for additional methylation-specific confirmatory testing. The diagnostic yield, the ROH pattern of eventually diagnosed cases and optimal thresholds for confirmatory testing were analyzed.</p><p><strong>Results: </strong>In the retrospective analysis, 15 true UPD cases of imprinting disorders were confirmed among 51 suspected cases by ROH detection. Pattern of ROH differed between confirmed UPD and non-UPD cases. Maximized yield and minimized false discovery rate of confirmatory UPD testing was achieved at the thresholds of >20 Mb or >25 % chromosomal coverage for interstitial ROH, and >5 Mb for terminal ROH. Current recommendation by ACMG was nearly optimal, though refined thresholds as proposed in this study could reduce the workload by 31 % without losing any true UPD diagnosis. Our refined thresholds remained optimal after independent evaluation in a prospective cohort.</p><p><strong>Conclusions: </strong>ROH identified in ES could implicate the presence of clinically relevant UPD. This study recommended size and coverage thresholds for confirmatory UPD testing after ROH detection in ES, contributing to the development of evidence-based reporting guidelines.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}