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International Journal of Infectious... Sep 2022Identifying pathogens in patients with pulmonary infection (PI) has always been a major challenge in medicine. Compared with sputum and throat swabs, bronchoalveolar... (Meta-Analysis)
Meta-Analysis Review
Diagnostic performance of metagenomic next-generation sequencing for the detection of pathogens in bronchoalveolar lavage fluid in patients with pulmonary infections: Systematic review and meta-analysis.
OBJECTIVES
Identifying pathogens in patients with pulmonary infection (PI) has always been a major challenge in medicine. Compared with sputum and throat swabs, bronchoalveolar lavage fluid (BALF) can better reflect the actual state of the lungs. However, there has not been a meta-analysis of the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) in detecting pathogens in BALF from patients with PIs.
METHODS
Data sources were PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure. The pooled sensitivity and specificity were estimated using random-effects or fixed-effect models. Subgroup analysis was performed to reveal the effect of potential explanatory factors on the diagnostic performance measures.
RESULTS
The pooled sensitivity was 78% (95% confidence interval [CI]: 67-87%; I = 92%) and the pooled specificity was 77% (95% CI: 64-94%; I = 74%) for mNGS. Subgroup analyses for the sensitivity of mNGS revealed that patients with PIs who were severely ill or immunocompromised significantly affected heterogeneity (P < 0.001). The positive detection rate of mNGS for pathogens in BALF of severely or immunocompromised pulmonary-infected patients was 92% (95% CI: 78-100%).
CONCLUSION
mNGS has high diagnostic performance for BALF pathogens in patients with PIs, especially in critically ill or immunocompromised patients.
Topics: Bronchoalveolar Lavage Fluid; High-Throughput Nucleotide Sequencing; Humans; Metagenome; Metagenomics; Pneumonia; Sensitivity and Specificity
PubMed: 35907477
DOI: 10.1016/j.ijid.2022.07.054 -
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 -
Frontiers in Cellular and Infection... 2022A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic method is particularly important for PJI. Recently, the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting PJI has attracted much attention, while the evidence of its accuracy is quite limited. Thus, this study aimed to evaluate the accuracy of mNGS for the diagnosis of PJI.
METHODS
We summarized published studies to identify the potential diagnostic value of mNGS for PJI patients by searching online databases using keywords such as "prosthetic joint infection", "PJI", and "metagenomic sequencing". Ten of 380 studies with 955 patients in total were included. The included studies provided sufficient data for the completion of 2-by-2 tables. We calculated the sensitivity, specificity, and area under the SROC curve (AUC) to evaluate mNGS for PJI diagnosis.
RESULTS
We found that the pooled diagnostic sensitivity and specificity of mNGS for PJI were 0.93 (95% CI, 0.83 to 0.97) and 0.95 (95% CI, 0.92 to 0.97), respectively. Positive and negative likelihood ratios were 18.3 (95% CI, 10.9 to 30.6) and 0.07 (95% CI, 0.03 to 0.18), respectively. The area under the curve was 0.96 (95% CI, 0.93 to 0.97).
CONCLUSION
Metagenomic next-generation sequencing displays high accuracy in the diagnosis of PJI, especially for culture-negative cases.
Topics: Arthritis, Infectious; High-Throughput Nucleotide Sequencing; Humans; Metagenomics; Prosthesis-Related Infections; Sensitivity and Specificity; Synovial Fluid
PubMed: 35755833
DOI: 10.3389/fcimb.2022.875822 -
Exploring and exploiting genetics and genomics for sweetpotato improvement: Status and perspectives.Plant Communications Sep 2022Sweetpotato (Ipomoea batatas (L.) Lam.) is one of the most important root crops cultivated worldwide. Because of its adaptability, high yield potential, and nutritional... (Review)
Review
Sweetpotato (Ipomoea batatas (L.) Lam.) is one of the most important root crops cultivated worldwide. Because of its adaptability, high yield potential, and nutritional value, sweetpotato has become an important food crop, particularly in developing countries. To ensure adequate crop yields to meet increasing demand, it is essential to enhance the tolerance of sweetpotato to environmental stresses and other yield-limiting factors. The highly heterozygous hexaploid genome of I. batatas complicates genetic studies and limits improvement of sweetpotato through traditional breeding. However, application of next-generation sequencing and high-throughput genotyping and phenotyping technologies to sweetpotato genetics and genomics research has provided new tools and resources for crop improvement. In this review, we discuss the genomics resources that are available for sweetpotato, including the current reference genome, databases, and available bioinformatics tools. We systematically review the current state of knowledge on the polyploid genetics of sweetpotato, including studies of its origin and germplasm diversity and the associated mapping of important agricultural traits. We then outline the conventional and molecular breeding approaches that have been applied to sweetpotato. Finally, we discuss future goals for genetic studies of sweetpotato and crop improvement via breeding in combination with state-of-the-art multi-omics approaches such as genomic selection and gene editing. These approaches will advance and accelerate genetic improvement of this important root crop and facilitate its sustainable global production.
Topics: Genomics; High-Throughput Nucleotide Sequencing; Ipomoea batatas; Plant Breeding; Polyploidy
PubMed: 35643086
DOI: 10.1016/j.xplc.2022.100332 -
Genetics in Medicine : Official Journal... Aug 2022The study aimed to determine the diagnostic yield, optimal timing, and methodology of next generation sequencing data reanalysis in suspected Mendelian disorders. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The study aimed to determine the diagnostic yield, optimal timing, and methodology of next generation sequencing data reanalysis in suspected Mendelian disorders.
METHODS
We conducted a systematic review and meta-analysis of studies that conducted data reanalysis in patients with suspected Mendelian disorders. Random effects model was used to pool the estimated outcome with subgroup analysis stratified by timing, sequencing methodology, sample size, segregation, use of research validation, and artificial intelligence (AI) variant curation tools.
RESULTS
A search of PubMed, Embase, Scopus, and Web of Science between 2007 and 2021 yielded 9327 articles, of which 29 were selected. Significant heterogeneity was noted between studies. Reanalysis had an overall diagnostic yield of 0.10 (95% CI = 0.06-0.13). Literature updates accounted for most new diagnoses. Diagnostic yield was higher after 24 months, although this was not statistically significant. Increased diagnoses were obtained with research validation and data sharing. AI-based tools did not adversely affect reanalysis diagnostic rate.
CONCLUSION
Next generation sequencing data reanalysis can improve diagnostic yield. Owing to the heterogeneity of the studies, the optimal time to reanalysis and the impact of AI-based tools could not be determined with confidence. We propose standardized guidelines for future studies to reduce heterogeneity and improve the quality of the conclusions.
Topics: Artificial Intelligence; High-Throughput Nucleotide Sequencing; Humans; Exome Sequencing
PubMed: 35550369
DOI: 10.1016/j.gim.2022.04.021 -
Neurosurgery Aug 2022Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker to capture tumor genetics in patients with brain tumors. Research into its clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker to capture tumor genetics in patients with brain tumors. Research into its clinical utility, however, has not been standardized because the sensitivity and specificity of ctDNA remain undefined.
OBJECTIVE
To (1) review the primary literature about ctDNA in adults with glioma to compare the sensitivity and specificity of ctDNA in the cerebrospinal fluid vs the plasma and (2) to evaluate the effect of tumor grade on detection of ctDNA.
METHODS
PRISMA-guided systematic review and meta-analysis was performed using published studies that assessed ctDNA in either plasma or cerebrospinal fluid among adult patients with confirmed glioma. Summary receiver operating characteristic curves were generated using the Rücker-Schumacher method, and area under the curve (AUC) was calculated.
RESULTS
Meta-analysis revealed improved biomarker performance for CSF (AUC = 0.947) vs plasma (AUC = 0.741) ctDNA, although this did not reach statistical significance ( P = .141). Qualitative analysis revealed greater sensitivities among single-allele PCR and small, targeted next-generation sequencing panels compared with broader panels. It additionally demonstrated higher sensitivity of ctDNA detection in high-grade vs low-grade gliomas, although these analyses were limited by a lack of specificity reporting in many studies.
CONCLUSION
ctDNA seems to be a highly sensitive and specific noninvasive biomarker among adults with gliomas. To maximize its performance, CSF should be studied with targeted genetic analysis platforms, particularly in high-grade gliomas. Further studies on ctDNA are needed to define its clinical utility in diagnosis, prognostication, glioblastoma pseudoprogression, and other scenarios wherein neoadjuvant therapies may be considered.
Topics: Adult; Biomarkers, Tumor; Circulating Tumor DNA; Glioma; High-Throughput Nucleotide Sequencing; Humans; Mutation
PubMed: 35535984
DOI: 10.1227/neu.0000000000001982 -
European Journal of Clinical... Jun 2022The early diagnosis of bacterial meningoencephalitis (BM/E) is difficult, and delay in diagnosis can cause complications leading to neurological impairment/death. In... (Meta-Analysis)
Meta-Analysis
The early diagnosis of bacterial meningoencephalitis (BM/E) is difficult, and delay in diagnosis can cause complications leading to neurological impairment/death. In cases of unexplained BM/E, the metagenomic NGS (mNGS) offers an advantage over conventional methods, especially when a rare pathogen is implicated or the patient is on antibiotics. This study aims to evaluate and compare the diagnostic efficacy of mNGS for the diagnosis of BM/E using cerebrospinal fluid (CSF) specimens versus a composite reference standard (CRS). The electronic databases (Embase, PubMed, and Web of Science) were searched up to 15 June 2021. Studies such as cohort, case-control, prospective, or retrospective studies that assessed the diagnostic efficacy of mNGS in suspected bacterial meningitis/encephalitis cases were included. Ten studies met the inclusion criteria, including three retrospective and seven prospective studies. The sensitivity of mNGS for diagnosis of BM/E from CSF samples ranged from 33 (95% CI: 13-62) to 98% (95% CI: 76-99). The specificity of mNGS ranged from 67 (95% CI: 55-78) to 98% (95% CI: 95-99). The estimated AUC (area under curve) by hierarchical summary receiver operating characteristic (HSROC) of the studies being analyzed was 0.912. The meta-regression analysis demonstrated that the different types of studies (single-center vs. multi-center) had an effect on the specificity of mNGS for BM/E compared with CRS (90% vs. 96%, meta-regression P < 0.05). The current analysis revealed moderate diagnostic accuracy of mNGS. This approach can be helpful, especially in cases of undiagnosed BM/E by identification of organism and subsequently accelerating the patient management.
Topics: High-Throughput Nucleotide Sequencing; Humans; Infectious Encephalitis; Meningitis, Bacterial; Meningoencephalitis; Metagenomics; Prospective Studies; Retrospective Studies; Sensitivity and Specificity
PubMed: 35474146
DOI: 10.1007/s10096-022-04445-0 -
The Journal of Pathology Jul 2022Precision oncology relies on the identification of targetable molecular alterations in tumor tissues. In many tumor types, a limited set of molecular tests is currently... (Review)
Review
Precision oncology relies on the identification of targetable molecular alterations in tumor tissues. In many tumor types, a limited set of molecular tests is currently part of standard diagnostic workflows. However, universal testing for all targetable alterations, especially rare ones, is limited by the cost and availability of molecular assays. From 2017 to 2021, multiple studies have shown that artificial intelligence (AI) methods can predict the probability of specific genetic alterations directly from conventional hematoxylin and eosin (H&E) tissue slides. Although these methods are currently less accurate than gold standard testing (e.g. immunohistochemistry, polymerase chain reaction or next-generation sequencing), they could be used as pre-screening tools to reduce the workload of genetic analyses. In this systematic literature review, we summarize the state of the art in predicting molecular alterations from H&E using AI. We found that AI methods perform reasonably well across multiple tumor types, although few algorithms have been broadly validated. In addition, we found that genetic alterations in FGFR, IDH, PIK3CA, BRAF, TP53, and DNA repair pathways are predictable from H&E in multiple tumor types, while many other genetic alterations have rarely been investigated or were only poorly predictable. Finally, we discuss the next steps for the implementation of AI-based surrogate tests in diagnostic workflows. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Artificial Intelligence; High-Throughput Nucleotide Sequencing; Humans; Mutation; Neoplasms; Precision Medicine
PubMed: 35342954
DOI: 10.1002/path.5898 -
Lung Cancer (Amsterdam, Netherlands) Apr 2022Next-generation sequencing (NGS) is able to identify targetable mutations to guide therapy and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA)... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of the adequacy of endobronchial ultrasound transbronchial needle aspiration for next-generation sequencing in patients with non-small cell lung cancer.
OBJECTIVES
Next-generation sequencing (NGS) is able to identify targetable mutations to guide therapy and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) offers a potential route to routinely obtain specimens for analysis. However, the suitability of EBUS-TBNA samples for NGS remains uncertain.
MATERIALS & METHODS
A search was conducted from inception till 28th August 2020. Pooled proportion of adequate EBUS-TBNA samples for NGS was obtained based on binomial distribution with Freeman-Tukey double-arcsine transformation. meta-analysis of means was conducted to determine mean weight of DNA extracted from EBUS-TBNA samples. meta-regression was performed to explore sources of heterogeneity. The random-effects model was used for all analyses to account for variation between studies.
RESULTS
Twenty-one studies comprising 1,175 patients were included. The pooled proportion of adequate EBUS-TBNA samples for NGS (yield) was 86.5% (95%-CI: 80.9% to 91.4%). Pooled mean weight of DNA extracted from EBUS-TBNA samples was 868.7 ng (95%-CI: 446.3 ng to 1291.1 ng). However, considerable heterogeneity (I = 84.0%, 97.1%) was found. Meta-regression with a mixed-effects negative exponential model showed an increased proportion of adequate EBUS-TBNA samples for NGS as mean number of passes increases (β = 0.495, 95%-CI 0.313 to 0.676, P < 0.001). Modelled yield rates were 77.3%, 86.2%, 91.6% and 94.9% at mean passes of 3, 4, 5 & 6 respectively.
CONCLUSION
EBUS-TBNA was associated with a high yield for NGS and the success of EBUS-TBNA sampling for NGS was proportional to the number of passes.
Topics: Bronchoscopy; Carcinoma, Non-Small-Cell Lung; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Endosonography; High-Throughput Nucleotide Sequencing; Humans; Lung Neoplasms
PubMed: 35151114
DOI: 10.1016/j.lungcan.2022.01.018 -
Transfusion Medicine Reviews Apr 2022Human platelet antigen (HPA) genotyping is performed in a number of clinical scenarios, including characterization of immune-mediated thrombocytopenia and provision of... (Meta-Analysis)
Meta-Analysis
Human platelet antigen (HPA) genotyping is performed in a number of clinical scenarios, including characterization of immune-mediated thrombocytopenia and provision of HPA-matched platelets. Current gold-standard methods for HPA genotyping utilize single nucleotide variant (SNV) based approaches. This review aims to ascertain if next generation sequencing (NGS) has reasonable grounds to replace SNV-based genotyping for HPA systems. A systematic review was conducted following a comprehensive literature search in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies were subjected to screening based on a defined set of inclusion/exclusion criteria. Study quality, characteristics and results were extracted and a meta-analysis was performed to assess the concordance of HPA genotyping results between NGS and the SNV-based comparators for HPA-1,-2,-3,-4,-5,-15. In total, 3374 potentially eligible articles were identified, only 6 of which were included in the meta-analysis. The pooled proportion agreement for the overall concordance of the 6 included studies was shown to be 0.998, 95%CI [0.995, 0.999], P < .001. The discrepancies between HPA genotypes obtained by the two platforms were due to allele dropout in real-time PCR, thus discordant results were in favor of NGS over SNV-based comparators. Currently available platforms for NGS are not without their limitations, including high upfront and ongoing costs, data management and storage, accurate variant calling and availability of appropriately trained staff. Despite the high level of concordance between NGS and current gold-standard methods, these significant challenges mean that NGS is currently not viable as a stand-alone technique for HPA typing.
Topics: Antigens, Human Platelet; Donor Selection; Genotype; High-Throughput Nucleotide Sequencing; Humans
PubMed: 35135721
DOI: 10.1016/j.tmrv.2022.01.001