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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 -
International Journal of Environmental... May 2021Patients with heart failure (HF) often present with signs and symptoms that are often nonspecific and with a wide differential diagnosis, making diagnosis and prognosis... (Review)
Review
Patients with heart failure (HF) often present with signs and symptoms that are often nonspecific and with a wide differential diagnosis, making diagnosis and prognosis of HF by clinical presentation alone challenging. Our knowledge on genetic diversity is rapidly evolving with high-throughput DNA sequencing technology, which makes a great potential for genetic biomarker development. The present review attempts to provide a comprehensive review on the modification of major genetic components in HF patients and to explore the potential application of these components as clinical biomarkers in the diagnosis and in monitoring the progress of HF. The literature search was conducted using six databases, resulting in the inclusion of eighteen studies in the review. The findings of these studies were summarized narratively. An appraisal of the reporting quality of the included studies was conducted using a twelve-item checklist adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. The findings showed that changes in genetic components in patients with HF compared to healthy controls could be noninvasive diagnostic or prognostic tools for HF with higher specificity and sensitivity in comparison with the traditional biomarkers. This review provided evidence for the potential of developing genetic biomarkers of HF.
Topics: Biomarkers; Genetic Markers; Heart Failure; Humans
PubMed: 34072866
DOI: 10.3390/ijerph18115904 -
PloS One 2021Before anti-EGFR therapy is given to patients with colorectal cancer, it is required to determine KRAS mutation status in tumor. When tumor tissue is not available,... (Meta-Analysis)
Meta-Analysis
The diagnostic accuracy of digital PCR, ARMS and NGS for detecting KRAS mutation in cell-free DNA of patients with colorectal cancer: A systematic review and meta-analysis.
INTRODUCTION
Before anti-EGFR therapy is given to patients with colorectal cancer, it is required to determine KRAS mutation status in tumor. When tumor tissue is not available, cell-free DNA (liquid biopsy) is commonly used as an alternative. Due to the low abundance of tumor-derived DNA in cell-free DNA samples, methods with high sensitivity were preferred, including digital polymerase chain reaction, amplification refractory mutation system and next-generation sequencing. The aim of this systemic review and meta-analysis was to investigate the accuracy of those methods in detecting KRAS mutation in cell-free DNA sample from patients with colorectal cancer.
METHODS
Literature search was performed in Pubmed, Embase, and Cochrane Library. After removing duplicates from the 170 publications found by literature search, eligible studies were identified using pre-defined criteria. Quality of the publications and relevant data were assessed and extracted thereafter. Meta-DiSc and STATA softwares were used to pool the accuracy parameters from the extracted data.
RESULTS
A total of 33 eligible studies were identified for this systemic review and meta-analysis. After pooling, the overall sensitivity, specificity, and diagnostic odds ratio were 0.77 (95%CI: 0.74-0.79), 0.87 (95%CI: 0.85-0.89), and 23.96 (95%CI: 13.72-41.84), respectively. The overall positive and negative likelihood ratios were 5.55 (95%CI: 3.76-8.19) and 0.29 (95%CI: 0.21-0.38), respectively. Area under curve of the summarized ROC curve was 0.8992.
CONCLUSION
Digital polymerase chain reaction, amplification refractory mutation system, and next-generation sequencing had overall high accuracy in detecting KRAS mutation in cell-free DNA sample. Large prospective randomized clinical trials are needed to further convince the accuracy and usefulness of KRAS mutation detection using cfDNA/liquid biopsy samples in clinical practice.
TRIAL REGISTRATION
PROSPERO CRD42020176682; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176682.
Topics: Circulating Tumor DNA; Colorectal Neoplasms; High-Throughput Nucleotide Sequencing; Humans; Mutation; Odds Ratio; Polymerase Chain Reaction; Proto-Oncogene Proteins p21(ras); Publication Bias; Publications; ROC Curve
PubMed: 33770081
DOI: 10.1371/journal.pone.0248775 -
Viruses Jan 2020A majority of emerging infectious diseases are of zoonotic origin. Metagenomic Next-Generation Sequencing (mNGS) has been employed to identify uncommon and novel...
A majority of emerging infectious diseases are of zoonotic origin. Metagenomic Next-Generation Sequencing (mNGS) has been employed to identify uncommon and novel infectious etiologies and characterize virus diversity in human, animal, and environmental samples. Here, we systematically reviewed studies that performed viral mNGS in common livestock (cattle, small ruminants, poultry, and pigs). We identified 2481 records and 120 records were ultimately included after a first and second screening. Pigs were the most frequently studied livestock and the virus diversity found in samples from poultry was the highest. Known animal viruses, zoonotic viruses, and novel viruses were reported in available literature, demonstrating the capacity of mNGS to identify both known and novel viruses. However, the coverage of metagenomic studies was patchy, with few data on the virome of small ruminants and respiratory virome of studied livestock. Essential metadata such as age of livestock and farm types were rarely mentioned in available literature, and only 10.8% of the datasets were publicly available. Developing a deeper understanding of livestock virome is crucial for detection of potential zoonotic and animal pathogens and One Health preparedness. Metagenomic studies can provide this background but only when combined with essential metadata and following the "FAIR" (Findable, Accessible, Interoperable, and Reusable) data principles.
Topics: Animals; Cattle; Communicable Diseases, Emerging; Disease Reservoirs; Farms; Genome, Viral; High-Throughput Nucleotide Sequencing; Livestock; Metagenome; Metagenomics; One Health; RNA, Viral; Virus Diseases; Viruses; Zoonoses
PubMed: 31963174
DOI: 10.3390/v12010107 -
Journal of Infection in Developing... Dec 2023Systematic evaluation of the diagnostic value of next generation sequencing (NGS) in sepsis etiology. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Systematic evaluation of the diagnostic value of next generation sequencing (NGS) in sepsis etiology.
METHODOLOGY
We conducted a systematic search on four databases (Web of Science, Cochrane, PubMed, and Embase) and compiled diagnostic experiments using NGS to evaluate sepsis etiology. Two researchers conducted research and obtained data independently.
RESULTS
Nine documents were included comprising 747 patients, 988 blood samples, 175 bronchoalveolar lavage fluid (BALF) samples, 16 cerebrospinal fluid samples, and one urine sample. The combined sensitivity of each study was 0.89 (95% CI: 0.82-0.95). The combined specificity was 0.40 (95% CI: 0.25-0.55). The combined positive likelihood ratio was 1.51 (95% CI: 1.18-1.98). The combined negative likelihood ratio was 0.28 (95% CI: 0.11-0.48). The diagnostic odds ratio (DOR) was 6.38 (95% CI: 2.53-15.32) and the area under the curve (AUC) was 0.84, (95% CI: 0.62-0.94).
CONCLUSIONS
Based on the data we collected, we found that compared with the blood culture technology, NGS has the advantages of high sensitivity and wide detection range, but its specificity was low. Further study is needed to confirm the value of NGS in the etiological diagnosis of patients with sepsis.
Topics: Humans; High-Throughput Nucleotide Sequencing; Sepsis; Area Under Curve; Blood Culture; Bronchoalveolar Lavage Fluid
PubMed: 38252719
DOI: 10.3855/jidc.18235 -
Journal of Orthopaedic Surgery and... Aug 2023Accurate diagnosis of prosthetic joint infection (PJI) enables early and effective treatment. However, there is currently no gold standard test for microbial detection... (Meta-Analysis)
Meta-Analysis
Comparison of microbial detection rates in microbial culture methods versus next-generation sequencing in patients with prosthetic joint infection: a systematic review and meta-analysis.
BACKGROUND
Accurate diagnosis of prosthetic joint infection (PJI) enables early and effective treatment. However, there is currently no gold standard test for microbial detection of PJI and traditional synovial fluid culture is relatively insensitive. Recently, it has been reported that sonicating fluid culture and next-generation sequencing (NGS) improve microbial detection rates. Hence, we performed a systematic review and meta-analysis to compare microbial detection rates in microbial culture methods with and without sonication versus NGS.
METHODS
We systematically searched EMBASE, PubMed, Scopus, CINAHL, and Ichushi databases and other sources (previous reviews) until August 2022. We evaluated the detection rates of pathogens in NGS and microbial cultures using samples of synovial or sonicated fluid.
RESULTS
Of the 170 citations identified for screening, nine studies were included. Pooled analysis indicated that NGS had the highest detection rate among the microbial detection methods (NGS vs. sonicated, odds ratios [OR] 5.09, 95% confidential interval [CI] 1.67-15.50; NGS vs. synovial, OR 4.52, 95% CI 2.86-7.16). Sonicated fluid culture showed a higher detection rate than synovial fluid culture (OR 2.11, 95% CI 1.23-3.62).
CONCLUSION
NGS might be useful as a screening tool for culture-negative patients. In clinical settings, sonicated fluid culture is a practical method for diagnosing PJI.
Topics: Humans; High-Throughput Nucleotide Sequencing; Arthritis, Infectious; Databases, Factual; Odds Ratio; Sonication
PubMed: 37587529
DOI: 10.1186/s13018-023-03973-5 -
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... 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 -
BMC Neurology Mar 2024MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT...
BACKGROUND
MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated.
METHODS
To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included.
RESULTS
We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions.
CONCLUSION
The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
Topics: Humans; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Glioma; Prognosis; Tumor Suppressor Proteins
PubMed: 38521933
DOI: 10.1186/s12883-024-03605-3 -
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