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Ultrasound in Obstetrics & Gynecology :... Jan 2022To determine the diagnostic yield of exome or genome sequencing (ES/GS) over chromosomal microarray analysis (CMA) in fetuses with increased nuchal translucency (NT) and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the diagnostic yield of exome or genome sequencing (ES/GS) over chromosomal microarray analysis (CMA) in fetuses with increased nuchal translucency (NT) and no concomitant anomalies.
METHODS
This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. PubMed, Scopus and Web of Science were searched for studies describing ES/GS in fetuses with isolated increased NT. Inclusion criteria were: (1) study written in English; (2) more than two fetuses with increased NT > 99 percentile and no concomitant anomalies; and (3) a negative CMA result considered as the reference standard. Only positive variants identified on ES/GS that were classified as likely pathogenic or pathogenic and determined to be causative of the fetal phenotype were considered. Risk was assessed as the pooled effect size by single-proportion analysis using random-effects modeling (weighted by inverse of variance).
RESULTS
Eleven studies reporting on the diagnostic yield of ES/GS in fetuses with isolated increased NT > 99 percentile were identified and included 309 cases. All studies were high quality according to Standards for Reporting of Diagnostic Accuracy. Overall, a pathogenic or likely pathogenic variant was identified on ES/GS in 15 fetuses, resulting in a pooled incremental yield of 4% (95% CI, 2-6%). Six (40%) of these fetuses had NT of 5 mm or more. The observed inheritance pattern was autosomal dominant in 12 cases, including four fetuses with Noonan syndrome, autosomal recessive in two cases and X-linked in one case.
CONCLUSIONS
There is a 4% incremental diagnostic yield of ES/GS over CMA in fetuses with increased NT > 99 percentile without a concomitant anomaly. It is unclear whether a NT cut-off higher than 3.5 mm may be more useful in case selection for ES/GS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Fetus; High-Throughput Nucleotide Sequencing; Humans; Microarray Analysis; Nuchal Translucency Measurement; Predictive Value of Tests; Pregnancy; Prenatal Diagnosis; Reference Values
PubMed: 34309942
DOI: 10.1002/uog.23746 -
Orphanet Journal of Rare Diseases Oct 2020Glycogen storage diseases (GSDs) with liver involvement are complex disorders with similar manifestations. Currently, the main diagnostic methods such as tissue... (Review)
Review
BACKGROUND
Glycogen storage diseases (GSDs) with liver involvement are complex disorders with similar manifestations. Currently, the main diagnostic methods such as tissue diagnosis, either histopathology or enzyme assay, are invasive. Meanwhile, GSDs are diseases with significant genetic heterogeneity, and gene-sequencing methods can be more useful. This systematic review aims to review the literature to assess the value of massively parallel sequencing in the diagnosis of GSDs on patients with previously undiagnosed hepatic involvement.
METHODS
Relevant studies identified in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science Core Collection databases up to July 2019 with no time and language restrictions. Publications were included in the review if they analyzed GSDs with hepatic involvement (GSD I, GSD III, GSD IV, GSD VI, GSD IX), using targeted gene sequencing (TGS) or exome sequencing (ES).
RESULTS
Eleven studies were included in this systematic review. ES demonstrated a 93% diagnostic yield. These methods correctly distinguished all types of pathogenic variants. The diagnostic yield of the TGS method was around 79.7%.
CONCLUSIONS
According to our results, TGS analysis can be considered as the first-line diagnostic method with valuable results and ES can be used to diagnose complex cases of GSD with liver involvement. Overall, these molecular methods are considered as accurate diagnostic tools, which expedite correct diagnosis and treatment with significant cost-effectiveness by reducing unnecessary and inaccurate tests.
PROSPERO REGISTRATION
CRD42020139931. Registered 8 January 2020.
Topics: Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Glycogen Storage Disease Type VI; High-Throughput Nucleotide Sequencing; Humans
PubMed: 33054851
DOI: 10.1186/s13023-020-01573-8 -
Journal of Clinical Microbiology Jan 2022The next-generation, short-read sequencing technologies that generate comprehensive, whole-genome data with single nucleotide resolution have already advanced...
The next-generation, short-read sequencing technologies that generate comprehensive, whole-genome data with single nucleotide resolution have already advanced tuberculosis diagnosis, treatment, surveillance, and source investigation. Their high costs, tedious and lengthy processes, and large equipment remain major hurdles for research use in high tuberculosis burden countries and implementation into routine care. The portable next-generation sequencing devices developed by Oxford Nanopore Technologies (ONT) are attractive alternatives due to their long-read sequence capability, compact low-cost hardware, and continued improvements in accuracy and throughput. A systematic review of the published literature demonstrated limited uptake of ONT sequencing in tuberculosis research and clinical care. Of the 12 eligible articles presenting ONT sequencing data on at least one Mycobacterium tuberculosis sample, four addressed software development for long-read ONT sequencing data with potential applications for M. tuberculosis. Only eight studies presented results of ONT sequencing of M. tuberculosis, of which five performed whole-genome and three did targeted sequencing. Based on these findings, we summarize the standard processes, reflect on the current limitations of ONT sequencing technology, and the research needed to overcome the main hurdles. The low capital cost, portable nature and continued improvement in the performance of ONT sequencing make it an attractive option for sequencing for research and clinical care, but limited data are available on its application in the tuberculosis field. Important research investment is needed to unleash the full potential of ONT sequencing for tuberculosis research and care.
Topics: High-Throughput Nucleotide Sequencing; Humans; Mycobacterium tuberculosis; Nanopore Sequencing; Sequence Analysis, DNA; Software
PubMed: 34133895
DOI: 10.1128/JCM.00646-21 -
JCO Precision Oncology Jul 2021We conducted this systematic review to evaluate the clinical outcomes associated with molecular tumor board (MTB) review in patients with cancer.
UNLABELLED
We conducted this systematic review to evaluate the clinical outcomes associated with molecular tumor board (MTB) review in patients with cancer.
METHODS
A systematic search of PubMed was performed to identify studies reporting clinical outcomes in patients with cancer who were reviewed by an MTB. To be included, studies had to report clinical outcomes, including clinical benefit, response, progression-free survival, or overall survival. Two reviewers independently selected studies and assessed quality with the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group or the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies depending on the type of study being reviewed.
RESULTS
Fourteen studies were included with a total of 3,328 patients with cancer. All studies included patients without standard-of-care treatment options and usually with multiple prior lines of therapy. In studies reporting response rates, patients receiving MTB-recommended therapy had overall response rates ranging from 0% to 67%. In the only trial powered on clinical outcome and including a control group, the group receiving MTB-recommended therapy had significantly improved rate of progression-free survival compared with those receiving conventional therapy.
CONCLUSION
Although data quality is limited by a lack of prospective randomized controlled trials, MTBs appear to improve clinical outcomes for patients with cancer. Future research should concentrate on prospective trials and standardization of approach and outcomes.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Clinical Decision-Making; DNA Mutational Analysis; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Medical Oncology; Molecular Targeted Therapy; Mutation; Neoplasms; Patient Care Team; Precision Medicine
PubMed: 34632252
DOI: 10.1200/PO.20.00495 -
BMC Infectious Diseases Feb 2024This meta-analysis focused on systematically assessing the clinical value of mNGS for infection in hematology patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This meta-analysis focused on systematically assessing the clinical value of mNGS for infection in hematology patients.
METHODS
We searched for studies that assessed the clinical value of mNGS for infection in hematology patients published in Embase, PubMed, Cochrane Library, Web of Science, and CNKI from inception to August 30, 2023. We compared the detection positive rate of pathogen for mNGS and conventional microbiological tests (CMTs). The diagnostic metrics, antibiotic adjustment rate and treatment effective rate were combined.
RESULTS
Twenty-two studies with 2325 patients were included. The positive rate of mNGS was higher than that of CMT (blood: 71.64% vs. 24.82%, P < 0.001; BALF: 89.86% vs. 20.78%, P < 0.001; mixed specimens: 82.02% vs. 28.12%, P < 0.001). The pooled sensitivity and specificity were 87% (95%CI: 81-91%) and 59% (95%CI: 43-72%), respectively. The reference standard/neutropenia and research type/reference standard may be sources of heterogeneity in sensitivity and specificity, respectively. The pooled antibiotic adjustment rate according to mNGS was 49.6% (95% CI: 41.8-57.4%), and the pooled effective rate was 80.9% (95% CI: 62.4-99.3%).
CONCLUSION
mNGS has high positive detection rates in hematology patients. mNGS can guide clinical antibiotic adjustments and improve prognosis, especially in China.
Topics: Humans; High-Throughput Nucleotide Sequencing; Neutropenia; Anti-Bacterial Agents; China; Hematology; Sensitivity and Specificity; Retrospective Studies
PubMed: 38326763
DOI: 10.1186/s12879-024-09073-x -
Reviews in Medical Virology Sep 2022Acute respiratory infection is the third most frequent cause of mortality worldwide, causing over 4.25 million deaths annually. Although most diagnosed acute respiratory... (Review)
Review
Detection of respiratory viruses directly from clinical samples using next-generation sequencing: A literature review of recent advances and potential for routine clinical use.
Acute respiratory infection is the third most frequent cause of mortality worldwide, causing over 4.25 million deaths annually. Although most diagnosed acute respiratory infections are thought to be of viral origin, the aetiology often remains unclear. The advent of next-generation sequencing (NGS) has revolutionised the field of virus discovery and identification, particularly in the detection of unknown respiratory viruses. We systematically reviewed the application of NGS technologies for detecting respiratory viruses from clinical samples and outline potential barriers to the routine clinical introduction of NGS. The five databases searched for studies published in English from 01 January 2010 to 01 February 2021, which led to the inclusion of 52 studies. A total of 14 different models of NGS platforms were summarised from included studies. Among these models, second-generation sequencing platforms (e.g., Illumina sequencers) were used in the majority of studies (41/52, 79%). Moreover, NGS platforms have proven successful in detecting a variety of respiratory viruses, including influenza A/B viruses (9/52, 17%), SARS-CoV-2 (21/52, 40%), parainfluenza virus (3/52, 6%), respiratory syncytial virus (1/52, 2%), human metapneumovirus (2/52, 4%), or a viral panel including other respiratory viruses (16/52, 31%). The review of NGS technologies used in previous studies indicates the advantages of NGS technologies in novel virus detection, virus typing, mutation identification, and infection cluster assessment. Although there remain some technical and ethical challenges associated with NGS use in clinical laboratories, NGS is a promising future tool to improve understanding of respiratory viruses and provide a more accurate diagnosis with simultaneous virus characterisation.
Topics: COVID-19; High-Throughput Nucleotide Sequencing; Humans; Influenza A virus; Influenza B virus; Respiratory Tract Infections; SARS-CoV-2
PubMed: 35775736
DOI: 10.1002/rmv.2375 -
Scientific Reports Jan 2022Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that in most cases occurs sporadic (sALS). The disease is not curable, and its pathogenesis... (Meta-Analysis)
Meta-Analysis
Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that in most cases occurs sporadic (sALS). The disease is not curable, and its pathogenesis mechanisms are not well understood yet. Given the intricacy of underlying molecular interactions and heterogeneity of ALS, the discovery of molecules contributing to disease onset and progression will open a new avenue for advancement in early diagnosis and therapeutic intervention. Here we conducted a meta-analysis of 12 circulating miRNA profiling studies using the robust rank aggregation (RRA) method, followed by enrichment analysis and experimental verification. We identified miR-451a and let-7f-5p as meta-signature miRNAs whose targets are involved in critical pathogenic pathways underlying ALS, including 'FoxO signaling pathway', 'MAPK signaling pathway', and 'apoptosis'. A systematic review of 7 circulating gene profiling studies elucidated that 241 genes up-regulated in sALS circulation with concomitant being targets of the meta-signature miRNAs. Protein-protein interaction (PPI) network analysis of the candidate targets using MCODE algorithm revealed the main subcluster is involved in multiple cascades eventually leads apoptosis, including 'positive regulation of neuron apoptosis. Besides, we validated the meta-analysis results using RT-qPCR. Indeed, relative expression analysis verified let-7f-5p and miR-338-3p as significantly down-regulated and up-regulated biomarkers in the plasma of sALS patients, respectively. Receiver operating characteristic (ROC) analysis also highlighted the let-7f-5p and miR-338-3p potential as robustness plasma biomarkers for diagnosis and potential therapeutic targets of sALS disease.
Topics: Algorithms; Amyotrophic Lateral Sclerosis; Biomarkers; Circulating MicroRNA; Down-Regulation; Empirical Research; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; MicroRNAs; Protein Interaction Maps; ROC Curve; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Transcriptome; Up-Regulation
PubMed: 35082326
DOI: 10.1038/s41598-022-05067-4 -
The Cochrane Database of Systematic... Mar 2021Glioblastoma is an aggressive form of brain cancer. Approximately five in 100 people with glioblastoma survive for five years past diagnosis. Glioblastomas that have a... (Meta-Analysis)
Meta-Analysis
Prognostic value of test(s) for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide.
BACKGROUND
Glioblastoma is an aggressive form of brain cancer. Approximately five in 100 people with glioblastoma survive for five years past diagnosis. Glioblastomas that have a particular modification to their DNA (called methylation) in a particular region (the O-methylguanine-DNA methyltransferase (MGMT) promoter) respond better to treatment with chemotherapy using a drug called temozolomide.
OBJECTIVES
To determine which method for assessing MGMT methylation status best predicts overall survival in people diagnosed with glioblastoma who are treated with temozolomide.
SEARCH METHODS
We searched MEDLINE, Embase, BIOSIS, Web of Science Conference Proceedings Citation Index to December 2018, and examined reference lists. For economic evaluation studies, we additionally searched NHS Economic Evaluation Database (EED) up to December 2014.
SELECTION CRITERIA
Eligible studies were longitudinal (cohort) studies of adults with diagnosed glioblastoma treated with temozolomide with/without radiotherapy/surgery. Studies had to have related MGMT status in tumour tissue (assessed by one or more method) with overall survival and presented results as hazard ratios or with sufficient information (e.g. Kaplan-Meier curves) for us to estimate hazard ratios. We focused mainly on studies comparing two or more methods, and listed brief details of articles that examined a single method of measuring MGMT promoter methylation. We also sought economic evaluations conducted alongside trials, modelling studies and cost analysis.
DATA COLLECTION AND ANALYSIS
Two review authors independently undertook all steps of the identification and data extraction process for multiple-method studies. We assessed risk of bias and applicability using our own modified and extended version of the QUality In Prognosis Studies (QUIPS) tool. We compared different techniques, exact promoter regions (5'-cytosine-phosphate-guanine-3' (CpG) sites) and thresholds for interpretation within studies by examining hazard ratios. We performed meta-analyses for comparisons of the three most commonly examined methods (immunohistochemistry (IHC), methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PSQ)), with ratios of hazard ratios (RHR), using an imputed value of the correlation between results based on the same individuals.
MAIN RESULTS
We included 32 independent cohorts involving 3474 people that compared two or more methods. We found evidence that MSP (CpG sites 76 to 80 and 84 to 87) is more prognostic than IHC for MGMT protein at varying thresholds (RHR 1.31, 95% confidence interval (CI) 1.01 to 1.71). We also found evidence that PSQ is more prognostic than IHC for MGMT protein at various thresholds (RHR 1.36, 95% CI 1.01 to 1.84). The data suggest that PSQ (mainly at CpG sites 74 to 78, using various thresholds) is slightly more prognostic than MSP at sites 76 to 80 and 84 to 87 (RHR 1.14, 95% CI 0.87 to 1.48). Many variants of PSQ have been compared, although we did not see any strong and consistent messages from the results. Targeting multiple CpG sites is likely to be more prognostic than targeting just one. In addition, we identified and summarised 190 articles describing a single method for measuring MGMT promoter methylation status.
AUTHORS' CONCLUSIONS
PSQ and MSP appear more prognostic for overall survival than IHC. Strong evidence is not available to draw conclusions with confidence about the best CpG sites or thresholds for quantitative methods. MSP has been studied mainly for CpG sites 76 to 80 and 84 to 87 and PSQ at CpG sites ranging from 72 to 95. A threshold of 9% for CpG sites 74 to 78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies making such comparisons.
Topics: Adult; Antineoplastic Agents, Alkylating; Bias; Brain Neoplasms; Cohort Studies; CpG Islands; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; Promoter Regions, Genetic; Temozolomide; Tumor Suppressor Proteins
PubMed: 33710615
DOI: 10.1002/14651858.CD013316.pub2 -
Clinical and Experimental Medicine Jun 2024To determine the diagnostic yield of Next-generation sequencing (NGS) in suspect Primary Immunodeficiencies Diseases (PIDs). This systematic review was conducted... (Meta-Analysis)
Meta-Analysis Review
To determine the diagnostic yield of Next-generation sequencing (NGS) in suspect Primary Immunodeficiencies Diseases (PIDs). This systematic review was conducted following PRISMA criteria. Searching Pubmed and Web of Science databases, the following keywords were used in the search: ("Next-generation sequencing") OR "whole exome sequencing" OR "whole genome sequencing") AND ("primary immunodeficiency disease" OR "PIDs"). We used STARD items to assess the risk of bias in the included studies. The meta-analysis included 29 studies with 5847 patients, revealing a pooled positive detection rate of 42% (95% CI 0.29-0.54, P < 0.001) for NGS in suspected PID cases. Subgroup analyses based on family history demonstrated a higher detection rate of 58% (95% CI 0.43-0.71) in patients with a family history compared to 33% (95% CI 0.21-0.46) in those without (P < 0.001). Stratification by disease types showed varied detection rates, with Severe Combined Immunodeficiency leading at 58% (P < 0.001). Among 253 PID-related genes, RAG1, ATM, BTK, and others constituted major contributors, with 34 genes not included in the 2022 IUIS gene list. The application of NGS in suspected PID patients can provide significant diagnostic results, especially in patients with a family history. Meanwhile, NGS performs excellently in accurately diagnosing disease types, and early identification of disease types can benefit patients in treatment.
Topics: Humans; High-Throughput Nucleotide Sequencing; Primary Immunodeficiency Diseases
PubMed: 38890201
DOI: 10.1007/s10238-024-01392-2 -
Cancer Medicine Oct 2019Small cell lung cancer (SCLC) is a highly invasive and lethal neuroendocrine tumor. Antiangiogenic drugs have been reported in the treatment of SCLC. We aimed to provide... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Small cell lung cancer (SCLC) is a highly invasive and lethal neuroendocrine tumor. Antiangiogenic drugs have been reported in the treatment of SCLC. We aimed to provide a comprehensive evaluation of the impact of angiogenic inhibitors on SCLC survival using network meta-analysis.
METHODS
The impact of five angiogenesis inhibitors, that is, vandetanib (Van), bevacizumab (Bev), Rh-endostatin (End), sunitinib (Sun), and thalidomide (Tha), on progression-free survival (PFS) and overall survival (OS) was evaluated by conducting a network meta-analysis. RNA sequencing data were downloaded from publicly available databases.
RESULTS
Nine phase II and III randomized controlled trials (RCTs), that involved 1599 participants, that investigated angiogenesis inhibitors in the treatment of SCLC were included in this meta-analysis. Sun and Bev achieved better PFS than Tha (Bev VS. Tha, HR = 0.88, 95% CI: 0.79-0.98, Sun VS. Tha, HR = 0.80, 95% CI: 0.65-1.00). Moreover, Sun and Bev were superior to placebo in terms of PFS (Bev VS. Placebo, HR = 0.89, 95%CI: 0.81-0.97, Sun VS. Placebo, HR = 0.81, 95% CI: 0.66-1.00). Based on this study, we found no significant difference of OS of SCLC. The angiogenesis pathway and expression of target genes were globally deactivated in SCLC tissue.
CONCLUSION
Results of this network meta-analysis indicate that the PFS outcome of SCLC with Sun or Bev drugs is superior to that of Tha. The improved therapeutic impact of angiogenesis inhibitors on SCLC needs more evidence, such as long-term observation in clinical trials, to be validated.
Topics: Angiogenesis Inhibitors; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; RNA-Seq; Randomized Controlled Trials as Topic; Small Cell Lung Carcinoma
PubMed: 31433125
DOI: 10.1002/cam4.2462