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Viruses Feb 2024There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS). PDR may contribute to the increased likelihood of virologic failure and the emergence of new resistance mutations. As SGS is gradually replaced by next-generation sequencing (NGS), it is necessary to assess the levels of PDR using NGS in ART-naïve patients systematically. NGS can detect the viral variants (low-abundance drug-resistant HIV-1 variants (LA-DRVs)) of virus quasi-species at levels below 20% that SGS may fail to detect. NGS has the potential to optimize current HIV drug resistance surveillance methods and inform future research directions. As the NGS technique has high sensitivity, it is highly likely that the level of pretreatment resistance would be underestimated using conventional techniques.
METHODS
For the systematic review and meta-analysis, we searched for original studies published in PubMed, Web of Science, Scopus, and Embase before 30 March 2023 that focused exclusively on the application of NGS in the detection of HIV drug resistance. Pooled prevalence estimates were calculated using a random effects model using the 'meta' package in R (version 4.2.3). We described drug resistance detected at five thresholds (>1%, 2%, 5%, 10%, and 20% of virus quasi-species). Chi-squared tests were used to analyze differences between the overall prevalence of PDR reported by SGS and NGS.
RESULTS
A total of 39 eligible studies were selected. The studies included a total of 15,242 ART-naïve individuals living with HIV. The prevalence of PDR was inversely correlated with the mutation detection threshold. The overall prevalence of PDR was 29.74% at the 1% threshold, 22.43% at the 2% threshold, 15.47% at the 5% threshold, 12.95% at the 10% threshold, and 11.08% at the 20% threshold. The prevalence of PDR to INSTIs was 1.22% (95%CI: 0.58-2.57), which is the lowest among the values for all antiretroviral drugs. The prevalence of LA-DRVs was 9.45%. At the 2% and 20% detection threshold, the prevalence of PDR was 22.43% and 11.08%, respectively. Resistance to PIs and INSTIs increased 5.52-fold and 7.08-fold, respectively, in those with a PDR threshold of 2% compared with those with PDR at 20%. However, resistance to NRTIs and NNRTIs increased 2.50-fold and 2.37-fold, respectively. There was a significant difference between the 2% and 5% threshold for detecting HIV drug resistance. There was no statistically significant difference between the results reported by SGS and NGS when using the 20% threshold for reporting resistance mutations.
CONCLUSION
In this study, we found that next-generation sequencing facilitates a more sensitive detection of HIV-1 drug resistance than SGS. The high prevalence of PDR emphasizes the importance of baseline resistance and assessing the threshold for optimal clinical detection using NGS.
Topics: Humans; HIV-1; Anti-HIV Agents; HIV Infections; Genotype; Drug Resistance, Viral; HIV Seropositivity; High-Throughput Nucleotide Sequencing; Prevalence; Mutation
PubMed: 38400015
DOI: 10.3390/v16020239 -
Clinical Genetics May 2023In recent years, massively parallel sequencing or next generation sequencing (NGS) has considerably changed both the research and diagnostic fields, and rapid... (Review)
Review
In recent years, massively parallel sequencing or next generation sequencing (NGS) has considerably changed both the research and diagnostic fields, and rapid developments have led to the combination of NGS techniques in clinical practice, ease of analysis, and detection of genetic mutations. This article aimed at reviewing the economic evaluation studies of the NGS techniques in the diagnosis of genetic diseases. In this systematic review, scientific databases (PubMed, EMBASE, Web of Science, Cochrane, Scopus, and CEA registry) were searched from 2005 to 2022 to identify the related literature on the economic evaluation of NGS techniques in the diagnosis of genetic diseases. Full-text reviews and data extraction were all performed by two independent researchers. The quality of all the articles included in this study was evaluated using the Checklist of Quality of Health Economic Studies (QHES). Out of 20 521 screened abstracts, 36 studies met the inclusion criteria. The mean score of the QHES checklist for the studies was 0.78 (high quality). Seventeen studies were conducted based on modeling. Cost-effectiveness analysis, cost-utility analysis, and cost-minimization analysis were done in 26 studies, 13 studies, and 1 study, respectively. Based on the available evidence and findings, exome sequencing, which is one of the NGS techniques, could have the potential to be used as a cost-effective genomic test to diagnose children with suspected genetic diseases. The results of the present study support the cost-effectiveness of exome sequencing in diagnosing suspected genetic disorders. However, the use of exome sequencing as a first- or second-line diagnostic test is still controversial. Most studies have been conducted in high-income countries, and research on the cost-effectiveness of NGS methods is recommended in low- and middle-income countries.
Topics: Child; Humans; Cost-Benefit Analysis; Mutation; Cost-Effectiveness Analysis; High-Throughput Nucleotide Sequencing
PubMed: 36808726
DOI: 10.1111/cge.14313 -
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 -
Value in Health : the Journal of the... May 2024To comprehensively identify and map an exhaustive list of value criteria for the assessment of next-generation sequencing/comprehensive genomic profiling (NGS/CGP), to... (Review)
Review
OBJECTIVES
To comprehensively identify and map an exhaustive list of value criteria for the assessment of next-generation sequencing/comprehensive genomic profiling (NGS/CGP), to be used as an aid in decision making.
METHODS
We conducted a systematic review to identify existing value frameworks (VFs) applicable to any type of healthcare technology. VFs and criteria were mapped to a previously published Latin American (LA) VF to harmonize definitions and identify additional criteria and or subcriteria. Based on this analysis, we extracted a comprehensive, evidence-based list of criteria and subcriteria to be considered in the design of a NGS/CGP VF.
RESULTS
A total of 42 additional VFs were compared with the LA VF, 88% were developed in high-income countries, 30% targeted genomic testing, and 16% specifically targeted oncology. A total of 242 criteria and subcriteria were extracted; 227 (94%) were fully/partially included in the LA VF; and 15 (6%) were new. Clinical benefit and economic aspects were the most common criteria. VFs oriented to genomic testing showed significant overlap with other VFs. Considering all criteria and subcriteria, a total of 18 criteria and 36 individual subcriteria were identified.
CONCLUSIONS
Our study provides an evidence-based set of criteria and subcriteria for healthcare decision making useful for NGS/CGP as well as other health technologies. The resulting list can be beneficial to inform decision making and will serve as a foundation to co-create a multistakeholder NGS/CGP VF that is aligned with the needs and values of health systems and could help to improve patient access to high-value technologies.
Topics: Humans; Genomics; High-Throughput Nucleotide Sequencing; Cost-Benefit Analysis; Genetic Testing; Decision Making
PubMed: 38403113
DOI: 10.1016/j.jval.2024.02.002 -
Alimentary Pharmacology & Therapeutics Mar 2020Helicobacter pylori is the most infamous constituent of the gastric microbiota and its presence is the strongest risk factor for gastric cancer and other gastroduodenal...
BACKGROUND
Helicobacter pylori is the most infamous constituent of the gastric microbiota and its presence is the strongest risk factor for gastric cancer and other gastroduodenal diseases. Although historically the healthy stomach was considered a sterile organ, we now know it is colonised with a complex microbiota. However, its role in health and disease is not well understood.
AIM
To systematically explore the literature on the gastric microbiota in health and disease as well as the gut microbiota after bariatric surgery.
METHODS
A systematic search of online bibliographic databases MEDLINE/EMBASE was performed between 1966 and February 2019 with screening in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomised controlled trials, cohort studies and observational studies were included if they reported next-generation sequencing derived microbiota analysis on gastric aspirate/tissue or stool samples (bariatric surgical outcomes).
RESULTS
Sixty-five papers were eligible for inclusion. With the exception of H pylori-induced conditions, overarching gastric microbiota signatures of health or disease could not be determined. Gastric carcinogenesis induces a progressively altered microbiota with an enrichment of oral and intestinal taxa as well as significant changes in host gastric mucin expression. Proton pump inhibitors usage increases gastric microbiota richness. Bariatric surgery is associated with an increase in potentially pathogenic proteobacterial species in patient stool samples.
CONCLUSION
While H pylori remains the single most important risk factor for gastric disease, its capacity to shape the collective gastric microbiota remains to be fully elucidated. Further studies are needed to explore the intricate host/microbial and microbial/microbial interplay.
Topics: Cohort Studies; DNA, Bacterial; Gastric Mucosa; Gastrointestinal Diseases; Gastrointestinal Microbiome; Health; Helicobacter Infections; Helicobacter pylori; High-Throughput Nucleotide Sequencing; Humans; Proton Pump Inhibitors; Risk Factors; Sequence Analysis, DNA; Stomach Neoplasms
PubMed: 32056247
DOI: 10.1111/apt.15650 -
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 -
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 -
International Journal of Molecular... Jan 2023Multiple Sclerosis (MS) is, to date, an incurable disease of the nervous system characterized by demyelination. Several genetic mutations are associated with the disease... (Review)
Review
Multiple Sclerosis (MS) is, to date, an incurable disease of the nervous system characterized by demyelination. Several genetic mutations are associated with the disease but they are not able to explain all the diagnosticated cases. Thus, it is suggested that altered gene expression may play a role in human pathologies. In this review, we explored the role of the transcriptomic profile in MS to investigate the main altered biological processes and pathways involved in the disease. Herein, we focused our attention on RNA-seq methods that in recent years are producing a huge amount of data rapidly replacing microarrays, both with bulk and single-cells. The studies evidenced that different MS stages have specific molecular signatures and non-coding RNAs may play a key role in the disease. Sex-dependence was observed before and after treatments used to alleviate symptomatology activating different biological processes in a drug-dependent manner. New pathways, such as neddylation, were found deregulated in MS and inflammation was linked to neuron degeneration areas through spatial transcriptomics. It is evident that the use of RNA-seq in the study of complex pathologies, such as MS, is a valid strategy to shed light on new involved mechanisms.
Topics: Humans; Transcriptome; Multiple Sclerosis; Gene Expression Profiling; RNA-Seq
PubMed: 36674968
DOI: 10.3390/ijms24021448 -
International Journal of Infectious... May 2024Early diagnosis of infectious diseases remains a challenge. This study assessed the diagnostic value of mNGS in infections and explored the effect of various factors on... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Early diagnosis of infectious diseases remains a challenge. This study assessed the diagnostic value of mNGS in infections and explored the effect of various factors on the accuracy of mNGS.
METHODS
An electronic article search of PubMed, Cochrane Library, and Embase was performed. A total of 85 papers were eligible for inclusion and analysis. Stata 12.0 was used for statistical calculation to evaluate the efficacy of mNGS for the diagnosis of infectious diseases.
RESULTS
The AUC of 85 studies was 0.88 (95%CI, 0.85-0.90). The AUC of the clinical comprehensive diagnosis and conventional test groups was 0.92 (95%CI, 0.89-0.94) and 0.82 (95%CI, 0.78-0.85), respectively. The results of subgroup analysis indicated that the PLR and NLR were 12.67 (95%CI, 6.01-26.70) and 0.05 (95%CI, 0.03-0.10), respectively, in arthrosis infections. The PLR was 24.41 (95%CI, 5.70-104.58) in central system infections and the NLR of immunocompromised patients was 0.08 (95%CI, 0.01-0.62).
CONCLUSION
mNGS demonstrated satisfactory diagnostic performance for infections, especially for bone and joint infections and central system infections. Moreover, mNGS also has a high value in the exclusion of infection in immunocompromised patients.
Topics: Humans; High-Throughput Nucleotide Sequencing; Arthritis, Infectious; Immunocompromised Host; Metagenome; Metagenomics; Sepsis; Communicable Diseases; Sensitivity and Specificity
PubMed: 38458421
DOI: 10.1016/j.ijid.2024.106996 -
International Journal of Molecular... Jan 2023The prediction of chronological age from methylation-based biomarkers represents one of the most promising applications in the field of forensic sciences. Age-prediction... (Review)
Review
The prediction of chronological age from methylation-based biomarkers represents one of the most promising applications in the field of forensic sciences. Age-prediction models developed so far are not easily applicable for forensic caseworkers. Among the several attempts to pursue this objective, the formulation of single-locus models might represent a good strategy. The present work aimed to develop an accurate single-locus model for age prediction exploiting , a gene for which epigenetic alterations are most highly correlated with age. We carried out a systematic review of different published pyrosequencing datasets in which methylation of the promoter was analysed to formulate age prediction models. Nine of these, with available datasets involving 2298 participants, were selected. We found that irrespective of which model was adopted, a very strong relationship between methylation levels and age exists. In particular, the model giving the best age-prediction accuracy was the gradient boosting regressor with a prediction error of about 5.5 years. The findings reported here strongly support the use of for the formulation of a single-locus epigenetic model, but the inclusion of additional, non-redundant markers is a fundamental requirement to apply a molecular model to forensic applications with more robust results.
Topics: Child, Preschool; Humans; Aging; CpG Islands; DNA Methylation; Epigenesis, Genetic; Forensic Genetics
PubMed: 36768576
DOI: 10.3390/ijms24032254