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Clinical Epigenetics 2016Multiple studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop powerful screening markers for cancer.... (Review)
Review
Multiple studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop powerful screening markers for cancer. This systematic review summarizes the current evidence on methylation studies that investigated methylation level of blood-derived DNA of breast cancer (BC) patients in comparison to healthy controls by conducting a systematic literature review in PubMed and Web of Science. Essential results, such as methylation levels of BC cases and healthy controls, values, and odds ratios, were extracted from these studies by two investigators independently. Overall, 45 publications met the inclusion criteria for this review. DNA from whole blood, as well as cell-free DNA (cfDNA) from serum or plasma, was used in these studies. The most common method used for measuring global DNA methylation was the investigation of repetitive elements as surrogates and the application of array-based genome-wide methylation analysis. For measuring gene-specific methylation level, methylation-specific PCR and pyrosequencing were the most frequently used methods. Epigenome-wide blood DNA hypomethylation in BC patients were reported in several studies; however, the evidence is still not conclusive. The most frequently investigated gene in whole blood was , which was found more frequently methylated in patients compared to controls. was the most widely investigated gene in cfDNA of serum or plasma, which was also found more frequently methylated in patients compared to controls. Several of the eligible studies reported the associations of global hypomethylation and increased BC risk. Studies investigated associations between gene-specific methylation and BC risk, while got heterogeneous results. But two studies reported that hypermethylation of gene was associated with increased BC risk, which suggest the potential use of this gene for BC risk stratification. Overall, our review suggests the possibility of using blood-based DNA methylation marker as promising marker for BC risk stratification, as several studies found associations between certain methylation level in blood and BC risk. However, so far, the evidence is still quite limited. Optimal markers are yet to be developed and promising results needed to be validated in prospective study cohorts and tested in large screening populations.
Topics: Biomarkers, Tumor; Breast Neoplasms; Cell-Free System; DNA Methylation; DNA, Neoplasm; Early Detection of Cancer; Female; Genomics; Humans; Mass Screening; Odds Ratio
PubMed: 27895805
DOI: 10.1186/s13148-016-0282-6 -
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 -
Trends in Cancer Sep 2020Next-generation sequencing (NGS) application in clinical practice requires the implementation of molecular tumor boards (MTBs). Starting from a systematic review of...
Next-generation sequencing (NGS) application in clinical practice requires the implementation of molecular tumor boards (MTBs). Starting from a systematic review of literature, we discuss the MTB-related key points: MTB aims and composition, types of tumors to discuss, types of molecular analyses, methods for classifying actionability, appropriate turnaround time, and cost management.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Clinical Decision-Making; Consensus; DNA Mutational Analysis; Drug Resistance, Neoplasm; Genetic Testing; Group Processes; High-Throughput Nucleotide Sequencing; Humans; Medical Oncology; Molecular Targeted Therapy; Mutation; Neoplasms; Patient Care Team; Precision Medicine
PubMed: 32517959
DOI: 10.1016/j.trecan.2020.05.008 -
Scientific Reports Dec 2022Many common pathogens are difficult or impossible to detect using conventional microbiological tests. However, the rapid and untargeted nature of metagenomic... (Meta-Analysis)
Meta-Analysis
Many common pathogens are difficult or impossible to detect using conventional microbiological tests. However, the rapid and untargeted nature of metagenomic next-generation sequencing (mNGS) appears to be a promising alternative. To perform a systematic review and meta-analysis of evidence regarding the diagnostic accuracy of mNGS in patients with infectious diseases. An electronic literature search of Embase, PubMed and Scopus databases was performed. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Summary receiver operating characteristics (sROC) and the area under the curve (AUC) were calculated; A random-effects model was used in cases of heterogeneity. A total of 20 papers were eligible for inclusion and synthesis. The sensitivity and specificity of diagnostic mNGS were 75% and 68%, respectively. The AUC from the SROC was 85%, corresponding to excellent performance. mNGS demonstrated satisfactory diagnostic performance for infections and yielded an overall detection rate superior to conventional methods.
Topics: Humans; Metagenomics; High-Throughput Nucleotide Sequencing; Communicable Diseases; Sensitivity and Specificity; Metagenome
PubMed: 36470909
DOI: 10.1038/s41598-022-25314-y -
International Journal of Laboratory... Apr 2022Membranopathies are a group of inherited blood disorders where the diagnosis could form a challenge due to phenotype-genotype heterogeneity. In this review, the usage... (Review)
Review
Membranopathies are a group of inherited blood disorders where the diagnosis could form a challenge due to phenotype-genotype heterogeneity. In this review, the usage and limitations of diagnostic methods for membranopathies in Asian countries were evaluated. A systematic review was done using articles from PubMed, Google Scholar, and EBSCO from 2000 to 2020. Thirty-six studies conducted in seven Asian countries had used different diagnostic methods to confirm membranopathies. In 58.3% of studies, full blood count (FBC), reticulocyte count, and peripheral blood smear (PBS) were used in preliminary diagnosis. The combination of the above three with osmotic fragility (OF) test was used in 38.8%. The flowcytometric osmotic fragility (FC-OF) test was used in 27.7% where it showed high sensitivity (92%-100%) and specificity (96%-98%). The eosin-5-maleimide (EMA) assay was used in 68.1% with high sensitivity (95%-100%) and specificity (93%-99.6%). About 36.1% of studies had used sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as a further diagnostic method to detect defective proteins. Genetic analysis to identify mutations was done using Sanger sequencing, next-generation sequencing (NGS), and whole-exome sequencing (WES) in 33.3%, 22.2%, and 13.8% of studies, respectively. The diagnostic yield of NGS ranged from 63% to 100%. Proteomics was used in 5.5% of studies to support the diagnosis of membranopathies. A single method could not diagnose all membranopathies. Next-generation sequencing, Sanger sequencing, and proteomics will supplement the well-established screening and confirmatory methods, but not replace them in hereditary hemolytic anemia assessment.
Topics: Anemia, Hemolytic, Congenital; Erythrocyte Membrane; High-Throughput Nucleotide Sequencing; Humans; Osmotic Fragility; Spherocytosis, Hereditary; Exome Sequencing
PubMed: 35068068
DOI: 10.1111/ijlh.13800 -
Journal of Assisted Reproduction and... Jul 2016The purpose of the review was to define the various diagnostic platforms currently available to perform preimplantation genetic testing for aneuploidy and describe in a... (Review)
Review
PURPOSE
The purpose of the review was to define the various diagnostic platforms currently available to perform preimplantation genetic testing for aneuploidy and describe in a clear and balanced manner the various strengths and weaknesses of these technologies.
METHODS
A systematic literature review was conducted. We used the terms "preimplantation genetic testing," "preimplantation genetic diagnosis," "preimplantation genetic screening," "preimplantation genetic diagnosis for aneuploidy," "PGD," "PGS," and "PGD-A" to search through PubMed, ScienceDirect, and Google Scholar from the year 2000 to April 2016. Bibliographies of articles were also searched for relevant studies. When possible, larger randomized controlled trials were used. However, for some emerging data, only data from meeting abstracts were available.
RESULTS
PGS is emerging as one of the most valuable tools to enhance pregnancy success with assisted reproductive technologies. While all of the current diagnostic platforms currently available have various advantages and disadvantages, some platforms, such as next-generation sequencing (NGS), are capable of evaluating far more data points than has been previously possible. The emerging complexity of different technologies, especially with the utilization of more sophisticated tools such as NGS, requires an understanding by clinicians in order to request the best test for their patients..
CONCLUSION
Ultimately, the choice of which diagnostic platform is utilized should be individualized to the needs of both the clinic and the patient. Such a decision must incorporate the risk tolerance of both the patient and provider, fiscal considerations, and other factors such as the ability to counsel patients on their testing results and how these may or may not impact clinical outcomes.
Topics: Aneuploidy; Blastocyst; Female; Fertilization in Vitro; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Pregnancy; Preimplantation Diagnosis; Real-Time Polymerase Chain Reaction
PubMed: 27299602
DOI: 10.1007/s10815-016-0740-2 -
Journal of Biomedical Science Jun 2018Next-generation sequencing (NGS) is a powerful and high-throughput method for the detection of viral mutations. This article provides a brief overview about optimization... (Review)
Review
BACKGROUND
Next-generation sequencing (NGS) is a powerful and high-throughput method for the detection of viral mutations. This article provides a brief overview about optimization of NGS analysis for hepatocellular carcinoma (HCC)-associated hepatitis B virus (HBV) mutations, and hepatocarcinogenesis of relevant mutations.
MAIN BODY
For the application of NGS analysis in the genome of HBV, four noteworthy steps were discovered in testing. First, a sample-specific reference sequence was the most effective mapping reference for NGS. Second, elongating the end of reference sequence improved mapping performance at the end of the genome. Third, resetting the origin of mapping reference sequence could probed deletion mutations and variants at a certain location with common mutations. Fourth, using a platform-specific cut-off value to distinguish authentic minority variants from technical artifacts was found to be highly effective. One hundred and sixty-seven HBV single nucleotide variants (SNVs) were found to be studied previously through a systematic literature review, and 12 SNVs were determined to be associated with HCC by meta-analysis. From comprehensive research using a HBV genome-wide NGS analysis, 60 NGS-defined HCC-associated SNVs with their pathogenic frequencies were identified, with 19 reported previously. All the 12 HCC-associated SNVs proved by meta-analysis were confirmed by NGS analysis, except for C1766T and T1768A which were mainly expressed in genotypes A and D, but including the subgroup analysis of A1762T. In the 41 novel NGS-defined HCC-associated SNVs, 31.7% (13/41) had cut-off values of SNV frequency lower than 20%. This showed that NGS could be used to detect HCC-associated SNVs with low SNV frequency. Most SNV II (the minor strains in the majority of non-HCC patients) had either low (< 20%) or high (> 80%) SNV frequencies in HCC patients, a characteristic U-shaped distribution pattern. The cut-off values of SNV frequency for HCC-associated SNVs represent their pathogenic frequencies. The pathogenic frequencies of HCC-associated SNV II also showed a U-shaped distribution. Hepatocarcinogenesis induced by HBV mutated proteins through cellular pathways was reviewed.
CONCLUSION
NGS analysis is useful to discover novel HCC-associated HBV SNVs, especially those with low SNV frequency. The hepatocarcinogenetic mechanisms of novel HCC-associated HBV SNVs defined by NGS analysis deserve further investigation.
Topics: Carcinogenesis; Carcinoma, Hepatocellular; Hepatitis B virus; High-Throughput Nucleotide Sequencing; Humans; Liver Neoplasms; Mutation
PubMed: 29859540
DOI: 10.1186/s12929-018-0442-4 -
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 -
American Journal of Ophthalmology May 2023Accurate genotyping of individuals with inherited retinal diseases (IRD) is essential for patient management and identifying suitable candidates for gene therapies. This... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Accurate genotyping of individuals with inherited retinal diseases (IRD) is essential for patient management and identifying suitable candidates for gene therapies. This study evaluated the diagnostic yield of next generation sequencing (NGS) in IRDs.
DESIGN
Systematic review and meta-analysis.
METHODS
This systematic review was prospectively registered (CRD42021293619). Ovid MEDLINE and Ovid Embase were searched on 6 June 2022. Clinical studies evaluating the diagnostic yield of NGS in individuals with IRDs were eligible for inclusion. Risk of bias assessment was performed. Studies were pooled using a random...effects inverse variance model. Sources of heterogeneity were explored using stratified analysis, meta-regression, and sensitivity analysis.
RESULTS
This study included 105 publications from 28 countries. Most studies (90 studies) used targeted gene panels. The diagnostic yield of NGS was 61.3% (95% confidence interval: 57.8-64.7%; 51 studies) in mixed IRD phenotypes, 58.2% (51.6-64.6%; 41 studies) in rod-cone dystrophies, 57.7% (46.8-68.3%; eight studies) in macular and cone/cone-rod dystrophies, and 47.6% (95% CI: 41.0-54.3%; four studies) in familial exudative vitreoretinopathy. For mixed IRD phenotypes, a higher diagnostic yield was achieved pooling studies published between 2018-2022 (64.2% [59.5-68.7%]), studies using exome sequencing (73.5% [58.9-86.1%]), and studies using the American College of Medical Genetics variant interpretation standards (65.6% [60.8-70.4%]).
CONCLUSION
The current diagnostic yield of NGS in IRDs is between 52-74%. The certainty of the evidence was judged as low or very low. A key limitation of the current evidence is the significant heterogeneity between studies. Adoption of standardized reporting guidelines could improve confidence in future meta-analyses.
Topics: Humans; High-Throughput Nucleotide Sequencing; Retinal Diseases; Retina; Cone-Rod Dystrophies; Phenotype
PubMed: 36592879
DOI: 10.1016/j.ajo.2022.12.027 -
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