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Knee Surgery, Sports Traumatology,... Sep 2023The purpose of this meta-analysis was to compare the diagnostic parameters of synovial next-generation sequencing (NGS) and cultures in diagnosing periprosthetic joint... (Meta-Analysis)
Meta-Analysis Review
Higher sensitivity and accuracy of synovial next-generation sequencing in comparison to culture in diagnosing periprosthetic joint infection: a systematic review and meta-analysis.
PURPOSE
The purpose of this meta-analysis was to compare the diagnostic parameters of synovial next-generation sequencing (NGS) and cultures in diagnosing periprosthetic joint infections (PJI).
METHODS
PubMed, Web of Science, Cochrane, and Google Scholar were searched from inception until 8 Jan 2022 for literature investigating the role of NGS in comparison to culture in the diagnosis of PJI. The studies were included if they investigated the diagnostic value of culture and NGS in diagnosing PJIs against the Musculoskeletal Infection Society (MSIS) criteria. Diagnostic parameters, such as sensitivity, specificity, positive predictive value, negative predictive value, positive-likelihood ratio, negative-likelihood ratio, accuracy, and area under the curve (AUC), were calculated for the included studies to evaluate the performance of NGS in comparison to culture in PJI diagnosis.
RESULTS
The total number of the included patients was 341 from seven articles. The pooled sensitivity, specificity, and diagnostic odds ratio of NGS were 94% (95% CI 91-97%), 89% (95% CI 82-95%), and 138.5 (95% CI 49.1-390.5), respectively. NGS has positive- and negative-likelihood ratios of 7.9 (95% CI 3.99-15.6) and 0.1 (95% CI 0.0-0.1), respectively. On the other hand, the pooled sensitivity, specificity, and diagnostic odds ratio of culture were 70% (95% CI 61-79%), 94% (95% CI 88-98%), and 28.0 (95% CI 12.6-62.2), respectively. The SROC curve for NGS showed that the accuracy (AUC) was 91.9%, and that the positive and negative predictive values were 8.6 (95% CI 5.0-19.5) and 0.1 (95% CI 0.0-0.1), respectively. While, culture SROC curve demonstrated that the accuracy (AUC) was 80.5% and the positive- and negative-likelihood ratio were 12.1 (95% CI 4.5-49.6) and 0.3 (95% CI 0.2-0.4).
CONCLUSIONS
NGS has a potential role in diagnosing hip and knee PJIs due to its high sensitivity, specificity, and accuracy. However, the sensitivity and specificity reported by the studies varied according to the time of synovial sampling (preoperative, postoperative, or mixed).
Topics: Humans; Knee Prosthesis; Hip Prosthesis; Prosthesis-Related Infections; Arthroplasty, Replacement, Knee; Sensitivity and Specificity; Synovial Fluid; High-Throughput Nucleotide Sequencing; Biomarkers
PubMed: 36244018
DOI: 10.1007/s00167-022-07196-9 -
Frontiers in Cellular and Infection... 2022() is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with in recent years. The disseminated infection of...
() is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with in recent years. The disseminated infection of can be life-threatening without timely and effective antifungal therapy. Rapid and accurate pathogenic microbiological diagnosis is particularly critical for these patients. A total of 505 patients with IEI were admitted to our hospital between January 2019 and June 2022, among whom was detected in 6 patients by metagenomic next-generation sequencing (mNGS), and their clinical and immunological characteristics were summarized. We performed a systematic literature review on infections with published immunodeficiency-related gene mutations. All patients in our cohort were confirmed to have genetic mutations in , , , , and . was detected in both the blood and lymph nodes of P1 with mutations, and the clinical manifestations were serious and included recurrent fever, weight loss, severe anemia, splenomegaly and lymphadenopathy, all requiring long-term antifungal therapy. These six patients received antifungal treatment, which relieved symptoms and improved imaging findings. Five patients survived, while one patient died of sepsis after hematopoietic stem cell transplantation. The application of mNGS methods for pathogen detection in IEI patients and comparison with traditional diagnosis methods were investigated. Traditional diagnostic methods and mNGS tests were performed simultaneously in 232 patients with IEI. Compared to the traditional methods, the sensitivity and specificity of mNGS in diagnosing infection were 100% and 98.7%, respectively. The reporting time for detection was approximately 26 hours by mNGS, 3-14 days by culture, and 6-11 days by histopathology. infection was first reported in IEI patients with gene mutation, which expanded the IEI lineage susceptible to . For IEI patients with infection, we highlight the application of mNGS in pathogenic detection. mNGS is recommended as a front-line diagnostic test for rapidly identifying pathogens in complex and severe infections.
Topics: Antifungal Agents; China; High-Throughput Nucleotide Sequencing; Humans; Mycoses; Talaromyces; Technology
PubMed: 36159645
DOI: 10.3389/fcimb.2022.987692 -
International Journal of Environmental... Sep 2022Recent advances in the development of next-generation sequencing (NGS) technologies, such as the 16S rRNA gene sequencing, have enabled significant progress in... (Review)
Review
Recent advances in the development of next-generation sequencing (NGS) technologies, such as the 16S rRNA gene sequencing, have enabled significant progress in characterizing the architecture of the oral microbiome. Understanding the taxonomic and functional components of the oral microbiome, especially during early childhood development, is becoming critical for identifying the interactions and adaptations of bacterial communities to dynamic conditions that may lead to the dysfunction of the host environment, thereby contributing to the onset and/or progression of a wide range of pathological conditions. We aimed to provide a comprehensive overview of the most recent evidence from studies of the oral microbiome of infants and young children, focusing on the development of oral microbiome in the window of birth to 18 years, focusing on infants. A systematic literature search was conducted in , , , and the WHO clinical trial website for relevant articles published between 2006 to 2022 to identify studies that examined genome-wide transcriptome of the oral microbiome in birth, early childhood, and adolescence performed via 16s rRNA sequence analysis. In addition, the references of selected articles were screened for other relevant studies. This systematic review was performed in accordance PRISMA guidelines. Data extraction and quality assessment were independently conducted by two authors, and a third author resolved discrepancies. Overall, 34 studies were included in this systematic review. Due to a considerable heterogeneity in study population, design, and outcome measures, a formal meta-analysis was not carried out. The current evidence indicates that a core microbiome is present in newborns, and it is stable in species number. Disparity about delivery mode influence are found. Further investigations are needed.
Topics: Adolescent; Bacteria; Child; Child, Preschool; High-Throughput Nucleotide Sequencing; Humans; Infant; Infant, Newborn; Microbiota; RNA, Ribosomal, 16S
PubMed: 36141674
DOI: 10.3390/ijerph191811403 -
Frontiers in Genetics 2022Legume crops provide significant nutrition to humans as a source of protein, omega-3 fatty acids as well as specific macro and micronutrients. Additionally, legumes...
Legume crops provide significant nutrition to humans as a source of protein, omega-3 fatty acids as well as specific macro and micronutrients. Additionally, legumes improve the cropping environment by replenishing the soil nitrogen content. Chickpeas are the second most significant staple legume food crop worldwide behind dry bean which contains 17%-24% protein, 41%-51% carbohydrate, and other important essential minerals, vitamins, dietary fiber, folate, β-carotene, anti-oxidants, micronutrients (phosphorus, calcium, magnesium, iron, and zinc) as well as linoleic and oleic unsaturated fatty acids. Despite these advantages, legumes are far behind cereals in terms of genetic improvement mainly due to far less effort, the bottlenecks of the narrow genetic base, and several biotic and abiotic factors in the scenario of changing climatic conditions. Measures are now called for beyond conventional breeding practices to strategically broadening of narrow genetic base utilizing chickpea wild relatives and improvement of cultivars through advanced breeding approaches with a focus on high yield productivity, biotic and abiotic stresses including climate resilience, and enhanced nutritional values. Desirable donors having such multiple traits have been identified using core and mini core collections from the cultivated gene pool and wild relatives of Chickpea. Several methods have been developed to address cross-species fertilization obstacles and to aid in inter-specific hybridization and introgression of the target gene sequences from wild species. Additionally, recent advances in "Omics" sciences along with high-throughput and precise phenotyping tools have made it easier to identify genes that regulate traits of interest. Next-generation sequencing technologies, whole-genome sequencing, transcriptomics, and differential genes expression profiling along with a plethora of novel techniques like single nucleotide polymorphism exploiting high-density genotyping by sequencing assays, simple sequence repeat markers, diversity array technology platform, and whole-genome re-sequencing technique led to the identification and development of QTLs and high-density trait mapping of the global chickpea germplasm. These altogether have helped in broadening the narrow genetic base of chickpeas.
PubMed: 36035111
DOI: 10.3389/fgene.2022.905771 -
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 -
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