Pub Date : 2023-07-01Epub Date: 2023-09-12DOI: 10.1080/14737159.2023.2255136
Loick P Kojom Foko, Jahnvi Jakhan, Geetika Narang, Vineeta Singh
Background: This review presents an overview of field findings on sequence variation of Plasmodium falciparum histidine-rich proteins 2/3 (PfHRP2/3) for which reference types (1-24) have been identified, and its critical impact on PfHRP2-based rapid diagnostic test (RDT) detection.
Research design and methods: This systematic review and meta-analysis was registered with PROSPERO, CRD42022316027, and conducted as per the PRISMA guidelines, and the methodological quality of studies was assessed.
Results: Of the 2184 records identified, 34 studies were included mostly from Africa (47.1%) and Asia (35.3%). The reference PfHRP2 types 1, 2, 3, 6, and 7 are invariably found at proportions ≥ 80-100% in all areas with the exception of The Americas where their proportion is very low. The proteins exhibited high diversity of variants/unknown types, especially for types 1, 2, 4, and 7. Eleven major PfHRP2 epitopes were found at pooled proportion > 90%. The existing models to predict RDT detection are greatly limited by the impact of factors such as low (very low) parasitemia, RDT brand, and PfHRP3 cross-reactivity. PfHRP2 length and presence/number of a given reference repeat type/variant did not seem to impact RDT detection.
Conclusions: PfHRP2/3 are highly polymorphic and current findings are insufficient, conflicting and not convincing enough to conclude on the role of PfHRP2/3 sequence polymorphism in PfHRP2-based RDT detection.
{"title":"Global polymorphism of <i>Plasmodium falciparum</i> histidine rich proteins 2/3 and impact on malaria rapid diagnostic test detection: a systematic review and meta-analysis.","authors":"Loick P Kojom Foko, Jahnvi Jakhan, Geetika Narang, Vineeta Singh","doi":"10.1080/14737159.2023.2255136","DOIUrl":"10.1080/14737159.2023.2255136","url":null,"abstract":"<p><strong>Background: </strong>This review presents an overview of field findings on sequence variation of <i>Plasmodium falciparum</i> histidine-rich proteins 2/3 (<i>Pf</i>HRP2/3) for which reference types (1-24) have been identified, and its critical impact on <i>Pf</i>HRP2-based rapid diagnostic test (RDT) detection.</p><p><strong>Research design and methods: </strong>This systematic review and meta-analysis was registered with PROSPERO, CRD42022316027, and conducted as per the PRISMA guidelines, and the methodological quality of studies was assessed.</p><p><strong>Results: </strong>Of the 2184 records identified, 34 studies were included mostly from Africa (47.1%) and Asia (35.3%). The reference <i>Pf</i>HRP2 types 1, 2, 3, 6, and 7 are invariably found at proportions ≥ 80-100% in all areas with the exception of The Americas where their proportion is very low. The proteins exhibited high diversity of variants/unknown types, especially for types 1, 2, 4, and 7. Eleven major <i>Pf</i>HRP2 epitopes were found at pooled proportion > 90%. The existing models to predict RDT detection are greatly limited by the impact of factors such as low (very low) parasitemia, RDT brand, and <i>Pf</i>HRP3 cross-reactivity. <i>Pf</i>HRP2 length and presence/number of a given reference repeat type/variant did not seem to impact RDT detection.</p><p><strong>Conclusions: </strong><i>Pf</i>HRP2/3 are highly polymorphic and current findings are insufficient, conflicting and not convincing enough to conclude on the role of <i>Pf</i>HRP2/3 sequence polymorphism in <i>Pf</i>HRP2-based RDT detection.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10580461","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}
Pub Date : 2023-07-01Epub Date: 2023-08-12DOI: 10.1080/14737159.2023.2245747
Jennifer Kerkhof, Cassandra Rastin, Laila Schenkel, Hanxin Lin, Bekim Sadikovic
Background: Comprehensive molecular diagnostics are highly dependent on the technical performance of next-generation sequencing (NGS) pipelines, which are assessed by data quality, cost, turnaround time, and accuracy of detecting a range of sequence and copy number variants.
Methods: A dataset of 285 clinically validated cases (205 retrospective and 80 prospective), carrying complex sequence and copy number variants and thousands of genetic polymorphisms underwent a clinical validation of the KAPA HyperChoice target enrichment system with parallel sample fidelity assessment across a number of NGS panels. The analysis included assessment of peripheral blood, urine, muscle and FFPE tissues.
Results: High-quality and exceptionally uniform data with 100% coverage of all targeted panels were obtained, resulting in complete sensitivity and specificity for all variant types across nearly all panels and tissue types. Overall reduction in cost and turnaround times was obtained with the implementation of a parallel genotyping sample fidelity system.
Conclusion: Results of the laboratory quality improvement study focused on a single NGS pipeline that includes both nuclear and mitochondrial genomes demonstrated utility in the clinical setting to assess a range of referral reasons, necessary due to the complex molecular etiology of human genetic disorders, while reducing costs and turnaround times.
{"title":"Clinical validation of a single NGS targeted panel pipeline using the KAPA HyperChoice system for detection of germline, somatic and mitochondrial sequence and copy number variants.","authors":"Jennifer Kerkhof, Cassandra Rastin, Laila Schenkel, Hanxin Lin, Bekim Sadikovic","doi":"10.1080/14737159.2023.2245747","DOIUrl":"10.1080/14737159.2023.2245747","url":null,"abstract":"<p><strong>Background: </strong>Comprehensive molecular diagnostics are highly dependent on the technical performance of next-generation sequencing (NGS) pipelines, which are assessed by data quality, cost, turnaround time, and accuracy of detecting a range of sequence and copy number variants.</p><p><strong>Methods: </strong>A dataset of 285 clinically validated cases (205 retrospective and 80 prospective), carrying complex sequence and copy number variants and thousands of genetic polymorphisms underwent a clinical validation of the KAPA HyperChoice target enrichment system with parallel sample fidelity assessment across a number of NGS panels. The analysis included assessment of peripheral blood, urine, muscle and FFPE tissues.</p><p><strong>Results: </strong>High-quality and exceptionally uniform data with 100% coverage of all targeted panels were obtained, resulting in complete sensitivity and specificity for all variant types across nearly all panels and tissue types. Overall reduction in cost and turnaround times was obtained with the implementation of a parallel genotyping sample fidelity system.</p><p><strong>Conclusion: </strong>Results of the laboratory quality improvement study focused on a single NGS pipeline that includes both nuclear and mitochondrial genomes demonstrated utility in the clinical setting to assess a range of referral reasons, necessary due to the complex molecular etiology of human genetic disorders, while reducing costs and turnaround times.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10117930","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}
Pub Date : 2023-07-01Epub Date: 2023-10-24DOI: 10.1080/14737159.2023.2260755
Tianyu Qiu, Xinxin Zhi, Shengxiang Ren
Introduction: Precision medicine based on the driver genes mutation status is the current systemic therapeutic paradigm in patients with lung cancer. Next-generation sequencing (NGS) has emerged as a powerful platform for molecular diagnosis by virtue of high-throughput and massively parallel sequencing. Liquid biopsy also enabled the dynamic monitoring and comprehensive profiling of lung cancer in a noninvasive manner. However, challenges remain in the field of technology and clinical applications, especially in the era of immunotherapy.
Areas covered: Here, we update the role of NGS in the context of lung cancer screening, molecular diagnosis, predictive and prognostic biomarkers, and guiding personalized treatment.
Expert opinion: The NGS application for actable genomic alternation has greatly changed the therapeutic landscape in patients with lung cancer including perioperative setting and advanced stage. Meanwhile, emerging evidence has shown the potential of other applications such as early screening and detection, and MRD. However, challenges remain such as the lack of standardized protocols across different platforms and bioinformatics analysis pipelines, and the complexity of interpreting and leveraging numerous genomic mutation messages for therapy selection. Future research is needed to overcome these challenges and expand the applications of NGS to other aspects such as immunotherapy.
{"title":"Recent advance of next-generation sequencing in patients with lung cancer.","authors":"Tianyu Qiu, Xinxin Zhi, Shengxiang Ren","doi":"10.1080/14737159.2023.2260755","DOIUrl":"10.1080/14737159.2023.2260755","url":null,"abstract":"<p><strong>Introduction: </strong>Precision medicine based on the driver genes mutation status is the current systemic therapeutic paradigm in patients with lung cancer. Next-generation sequencing (NGS) has emerged as a powerful platform for molecular diagnosis by virtue of high-throughput and massively parallel sequencing. Liquid biopsy also enabled the dynamic monitoring and comprehensive profiling of lung cancer in a noninvasive manner. However, challenges remain in the field of technology and clinical applications, especially in the era of immunotherapy.</p><p><strong>Areas covered: </strong>Here, we update the role of NGS in the context of lung cancer screening, molecular diagnosis, predictive and prognostic biomarkers, and guiding personalized treatment.</p><p><strong>Expert opinion: </strong>The NGS application for actable genomic alternation has greatly changed the therapeutic landscape in patients with lung cancer including perioperative setting and advanced stage. Meanwhile, emerging evidence has shown the potential of other applications such as early screening and detection, and MRD. However, challenges remain such as the lack of standardized protocols across different platforms and bioinformatics analysis pipelines, and the complexity of interpreting and leveraging numerous genomic mutation messages for therapy selection. Future research is needed to overcome these challenges and expand the applications of NGS to other aspects such as immunotherapy.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107617","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}
Pub Date : 2023-07-01Epub Date: 2023-12-15DOI: 10.1080/14737159.2023.2277377
Jianhua Gu, Feifan He, Gary M Clifford, Minjuan Li, Zhiyuan Fan, Xinqing Li, Shaoming Wang, Wenqiang Wei
Introduction: This study aimed to update the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC).
Methods: We searched PubMed, Embase, and Cochrane Library from 1990 to December 2021 to identify prospective studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and GC.
Results: Including 27 studies, findings indicated a strong link between H. pylori and non-cardia gastric cancer (NCGC) in both Europe/North America (OR=5.37, 95%CI:4.39-6.57) and Asia (OR = 2.50, 95%CI:1.89-3.32), and a positive association with cardia gastric cancer (CGC) in Asia (OR = 1.74, 95%CI:1.38-2.19), but an inverse association in European/American populations (OR = 0.64, 95%CI: 0.51 to 0.79). Furthermore, the strength of association was greater in studies that detected H. pylori by immunoblotting versus ELISA, and also in studies testing for H. pylori detection further back in time prior to cancer diagnosis (Ptrend<0.05). Approximately 79% of NCGC in Asia and 87% in Europe/North America, along with 62% of CGC in Asia, could be attributable to H. pylori infection.
Conclusions: The meta-analysis supports the significant attributable risk of H. pylori infection for GC and underscores the potential impact of targeting H. pylori in GC prevention programs.
{"title":"A systematic review and meta-analysis on the relative and attributable risk of <i>Helicobacter pylori</i> infection and cardia and non-cardia gastric cancer.","authors":"Jianhua Gu, Feifan He, Gary M Clifford, Minjuan Li, Zhiyuan Fan, Xinqing Li, Shaoming Wang, Wenqiang Wei","doi":"10.1080/14737159.2023.2277377","DOIUrl":"10.1080/14737159.2023.2277377","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to update the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC).</p><p><strong>Methods: </strong>We searched PubMed, Embase, and Cochrane Library from 1990 to December 2021 to identify prospective studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and GC.</p><p><strong>Results: </strong>Including 27 studies, findings indicated a strong link between H. pylori and non-cardia gastric cancer (NCGC) in both Europe/North America (OR=5.37, 95%CI:4.39-6.57) and Asia (OR = 2.50, 95%CI:1.89-3.32), and a positive association with cardia gastric cancer (CGC) in Asia (OR = 1.74, 95%CI:1.38-2.19), but an inverse association in European/American populations (OR = 0.64, 95%CI: 0.51 to 0.79). Furthermore, the strength of association was greater in studies that detected H. pylori by immunoblotting versus ELISA, and also in studies testing for H. pylori detection further back in time prior to cancer diagnosis (Ptrend<0.05). Approximately 79% of NCGC in Asia and 87% in Europe/North America, along with 62% of CGC in Asia, could be attributable to H. pylori infection.</p><p><strong>Conclusions: </strong>The meta-analysis supports the significant attributable risk of H. pylori infection for GC and underscores the potential impact of targeting H. pylori in GC prevention programs.</p><p><strong>Prospero registration: </strong>CRD42021274120.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411259","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}
Pub Date : 2023-07-01Epub Date: 2023-12-15DOI: 10.1080/14737159.2023.2277373
Yvonne Couch
Introduction: The hunt for new biomarkers - for the diagnosis of subcategories of disease, or for the monitoring of the efficacy of novel therapeutics - is an increasingly relevant challenge in the current era of precision medicine. In neurodegenerative research, the aim is to look for simple tools which can predict cognitive or motor decline early, and to determine whether these can also be used to test the efficacy of new interventions. Extracellular vesicles (EVs) are thought to play an important role in intercellular communication and have been shown to play a vital role in a number of diseases.
Areas covered: The aim of this review is to examine what we know about EVs in neurodegeneration and to discuss their potential to be diagnostic and prognostic biomarkers in the future. It will cover the techniques used to isolate and study EVs and what is currently known about their presence in neurodegenerative diseases. In particular, we will discuss what is required for standardization in biomarker research, and the challenges associated with using EVs within this framework.
Expert opinion: The technical challenges associated with isolating EVs consistently, combined with the complex techniques required for their efficient analysis, might preclude 'pure' EV populations from being used as effective biomarkers. Whilst biomarker discovery is important for more effective diagnosis, monitoring, prediction and prognosis in neurodegenerative disease, reproducibility and ease-of-use should be the priorities.
{"title":"Challenges associated with using extracellular vesicles as biomarkers in neurodegenerative disease.","authors":"Yvonne Couch","doi":"10.1080/14737159.2023.2277373","DOIUrl":"10.1080/14737159.2023.2277373","url":null,"abstract":"<p><strong>Introduction: </strong>The hunt for new biomarkers - for the diagnosis of subcategories of disease, or for the monitoring of the efficacy of novel therapeutics - is an increasingly relevant challenge in the current era of precision medicine. In neurodegenerative research, the aim is to look for simple tools which can predict cognitive or motor decline early, and to determine whether these can also be used to test the efficacy of new interventions. Extracellular vesicles (EVs) are thought to play an important role in intercellular communication and have been shown to play a vital role in a number of diseases.</p><p><strong>Areas covered: </strong>The aim of this review is to examine what we know about EVs in neurodegeneration and to discuss their potential to be diagnostic and prognostic biomarkers in the future. It will cover the techniques used to isolate and study EVs and what is currently known about their presence in neurodegenerative diseases. In particular, we will discuss what is required for standardization in biomarker research, and the challenges associated with using EVs within this framework.</p><p><strong>Expert opinion: </strong>The technical challenges associated with isolating EVs consistently, combined with the complex techniques required for their efficient analysis, might preclude 'pure' EV populations from being used as effective biomarkers. Whilst biomarker discovery is important for more effective diagnosis, monitoring, prediction and prognosis in neurodegenerative disease, reproducibility and ease-of-use should be the priorities.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71422007","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}
{"title":"A charming molecular profile in the wrong tissue: the pathologist in the era of molecular diagnostics in the gastrointestinal tract.","authors":"Paola Parente, Federica Grillo, Alessandro Vanoli, Luca Mastracci, Matteo Fassan","doi":"10.1080/14737159.2023.2288267","DOIUrl":"10.1080/14737159.2023.2288267","url":null,"abstract":"","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298814","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}
Pub Date : 2023-07-01Epub Date: 2023-07-17DOI: 10.1080/14737159.2023.2236022
Rongwei Lei, Nga Thai, Yaxi Li, Michelle Petri, Chandra Mohan
Objectives: Urinary activated leukocyte cell adhesion molecule (uALCAM) is emerging as an outstanding biomarker for active lupus nephritis (ALN). This study aims to evaluate the analytic performance of the human ALCAM ELISA as an assay method to quantify uALCAM in patients with lupus nephritis.
Methods: A commercially available human ALCAM ELISA kit was validated for its analytical performance as per Clinical & Laboratory Standards Institute guidelines.
Results: Assaying 30 sets of serial dilutions of ALCAM exhibited an average CV of 10% and 97%-105% recovery. The assay also exhibited overall acceptable imprecision (CV < 20%) in day-to-day, site-to-site, and lot-to-lot reproducibility. The assay exhibited a reportable range from 4018 pg/ml down to 62 pg/ml with an r2 of 0.999 in urine, with a limit of detection of 16-45 pg/ml. Most tested chemicals did not interfere with the assay, and no diurnal variations were observed in uALCAM levels. uALCAM was stable for at least 3 months at -20°C or -80°C.
Conclusion: This analytic-validated uALCAM ELISA may provide physicians with an accurate and reliable tool for use in early detection of renal involvement in lupus, routine outpatient monitoring of disease activity, and long-term prognostication.
{"title":"Analytical validation of urine ALCAM ELISA as a test for lupus nephritis.","authors":"Rongwei Lei, Nga Thai, Yaxi Li, Michelle Petri, Chandra Mohan","doi":"10.1080/14737159.2023.2236022","DOIUrl":"10.1080/14737159.2023.2236022","url":null,"abstract":"<p><strong>Objectives: </strong>Urinary activated leukocyte cell adhesion molecule (uALCAM) is emerging as an outstanding biomarker for active lupus nephritis (ALN). This study aims to evaluate the analytic performance of the human ALCAM ELISA as an assay method to quantify uALCAM in patients with lupus nephritis.</p><p><strong>Methods: </strong>A commercially available human ALCAM ELISA kit was validated for its analytical performance as per Clinical & Laboratory Standards Institute guidelines.</p><p><strong>Results: </strong>Assaying 30 sets of serial dilutions of ALCAM exhibited an average CV of 10% and 97%-105% recovery. The assay also exhibited overall acceptable imprecision (CV < 20%) in day-to-day, site-to-site, and lot-to-lot reproducibility. The assay exhibited a reportable range from 4018 pg/ml down to 62 pg/ml with an r<sup>2</sup> of 0.999 in urine, with a limit of detection of 16-45 pg/ml. Most tested chemicals did not interfere with the assay, and no diurnal variations were observed in uALCAM levels. uALCAM was stable for at least 3 months at -20°C or -80°C.</p><p><strong>Conclusion: </strong>This analytic-validated uALCAM ELISA may provide physicians with an accurate and reliable tool for use in early detection of renal involvement in lupus, routine outpatient monitoring of disease activity, and long-term prognostication.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10103370","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}
Pub Date : 2023-07-01Epub Date: 2023-08-29DOI: 10.1080/14737159.2023.2241365
William L Macken, Micol Falabella, Chiara Pizzamiglio, Cathy E Woodward, Elizabeth Scotchman, Lyn S Chitty, James M Polke, Enrico Bugiardini, Michael G Hanna, Jana Vandrovcova, Natalie Chandler, Robyn Labrum, Robert D S Pitceathly
Introduction: Primary mitochondrial diseases (PMDs) comprise a large and heterogeneous group of genetic diseases that result from pathogenic variants in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Widespread adoption of next-generation sequencing (NGS) has improved the efficiency and accuracy of mtDNA diagnoses; however, several challenges remain.
Areas covered: In this review, we briefly summarize the current state of the art in molecular diagnostics for mtDNA and consider the implications of improved whole genome sequencing (WGS), bioinformatic techniques, and the adoption of long-read sequencing, for PMD diagnostics.
Expert opinion: We anticipate that the application of PCR-free WGS from blood DNA will increase in diagnostic laboratories, while for adults with myopathic presentations, WGS from muscle DNA may become more widespread. Improved bioinformatic strategies will enhance WGS data interrogation, with more accurate delineation of mtDNA and NUMTs (nuclear mitochondrial DNA segments) in WGS data, superior coverage uniformity, indirect measurement of mtDNA copy number, and more accurate interpretation of heteroplasmic large-scale rearrangements (LSRs). Separately, the adoption of diagnostic long-read sequencing could offer greater resolution of complex LSRs and the opportunity to phase heteroplasmic variants.
{"title":"Enhanced mitochondrial genome analysis: bioinformatic and long-read sequencing advances and their diagnostic implications.","authors":"William L Macken, Micol Falabella, Chiara Pizzamiglio, Cathy E Woodward, Elizabeth Scotchman, Lyn S Chitty, James M Polke, Enrico Bugiardini, Michael G Hanna, Jana Vandrovcova, Natalie Chandler, Robyn Labrum, Robert D S Pitceathly","doi":"10.1080/14737159.2023.2241365","DOIUrl":"10.1080/14737159.2023.2241365","url":null,"abstract":"<p><strong>Introduction: </strong>Primary mitochondrial diseases (PMDs) comprise a large and heterogeneous group of genetic diseases that result from pathogenic variants in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Widespread adoption of next-generation sequencing (NGS) has improved the efficiency and accuracy of mtDNA diagnoses; however, several challenges remain.</p><p><strong>Areas covered: </strong>In this review, we briefly summarize the current state of the art in molecular diagnostics for mtDNA and consider the implications of improved whole genome sequencing (WGS), bioinformatic techniques, and the adoption of long-read sequencing, for PMD diagnostics.</p><p><strong>Expert opinion: </strong>We anticipate that the application of PCR-free WGS from blood DNA will increase in diagnostic laboratories, while for adults with myopathic presentations, WGS from muscle DNA may become more widespread. Improved bioinformatic strategies will enhance WGS data interrogation, with more accurate delineation of mtDNA and NUMTs (nuclear mitochondrial DNA segments) in WGS data, superior coverage uniformity, indirect measurement of mtDNA copy number, and more accurate interpretation of heteroplasmic large-scale rearrangements (LSRs). Separately, the adoption of diagnostic long-read sequencing could offer greater resolution of complex LSRs and the opportunity to phase heteroplasmic variants.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175376","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}
Pub Date : 2023-07-01Epub Date: 2023-12-15DOI: 10.1080/14737159.2023.2277366
Matteo Ferro, Bernardo Rocco, Martina Maggi, Giuseppe Lucarelli, Ugo Giovanni Falagario, Francesco Del Giudice, Felice Crocetto, Biagio Barone, Evelina La Civita, Francesco Lasorsa, Antonio Brescia, Michele Catellani, Gian Maria Busetto, Octavian Sabin Tataru, Daniela Terracciano
Introduction: New potential biomarkers to pre-intervention identification of a clinically significant prostate cancer (csPCa) will prevent overdiagnosis and overtreatment and limit quality of life impairment of PCa patients.
Areas covered: We have developed a comprehensive review focusing our research on the increasing knowledge of the role of SelectMDX® in csPCa detection. Areas identified as clinically relevant are the ability of SelectMDX® to predict csPCa in active surveillance setting, its predictive ability when combined with multiparametric MRI and the role of SelectMDX® in the landscape of urinary biomarkers.
Expert opinion: Several PCa biomarkers have been developed either alone or in combination with clinical variables to improve csPCa detection. SelectMDX® score includes genomic markers, age, PSA, prostate volume, and digital rectal examination. Several studies have shown consistency in the ability to improve detection of csPCa, avoidance of unnecessary prostate biopsies, helpful in decision-making for clinical benefit of PCa patients with future well designed, and impactful studies.
{"title":"Beyond blood biomarkers: the role of SelectMDX in clinically significant prostate cancer identification.","authors":"Matteo Ferro, Bernardo Rocco, Martina Maggi, Giuseppe Lucarelli, Ugo Giovanni Falagario, Francesco Del Giudice, Felice Crocetto, Biagio Barone, Evelina La Civita, Francesco Lasorsa, Antonio Brescia, Michele Catellani, Gian Maria Busetto, Octavian Sabin Tataru, Daniela Terracciano","doi":"10.1080/14737159.2023.2277366","DOIUrl":"10.1080/14737159.2023.2277366","url":null,"abstract":"<p><strong>Introduction: </strong>New potential biomarkers to pre-intervention identification of a clinically significant prostate cancer (csPCa) will prevent overdiagnosis and overtreatment and limit quality of life impairment of PCa patients.</p><p><strong>Areas covered: </strong>We have developed a comprehensive review focusing our research on the increasing knowledge of the role of SelectMDX® in csPCa detection. Areas identified as clinically relevant are the ability of SelectMDX® to predict csPCa in active surveillance setting, its predictive ability when combined with multiparametric MRI and the role of SelectMDX® in the landscape of urinary biomarkers.</p><p><strong>Expert opinion: </strong>Several PCa biomarkers have been developed either alone or in combination with clinical variables to improve csPCa detection. SelectMDX® score includes genomic markers, age, PSA, prostate volume, and digital rectal examination. Several studies have shown consistency in the ability to improve detection of csPCa, avoidance of unnecessary prostate biopsies, helpful in decision-making for clinical benefit of PCa patients with future well designed, and impactful studies.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66783727","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}
Pub Date : 2023-07-01Epub Date: 2023-12-15DOI: 10.1080/14737159.2023.2277371
Mariaelena Pierobon, Emanuel F Petricoin
{"title":"Functional proteomic analysis, a missing piece for understanding clonal evolution and cooperation in the tissue microecology.","authors":"Mariaelena Pierobon, Emanuel F Petricoin","doi":"10.1080/14737159.2023.2277371","DOIUrl":"10.1080/14737159.2023.2277371","url":null,"abstract":"","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411260","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}