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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 -
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 -
Expert Review of Molecular Diagnostics Jan 2023This systematic review was designed to summarize the findings on expression and mutation of genes in ovarian cancer (OC) patients, focusing on mutation detection...
INTRODUCTION
This systematic review was designed to summarize the findings on expression and mutation of genes in ovarian cancer (OC) patients, focusing on mutation detection technology and taking clinical decisions for better treatment.
AREAS COVERED
We conducted a systematic review by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses document selection guidelines for the document selection process and the PICOT standard for developing the keywords to search for. A total of 5729 publications were included, and 50 articles were put into the final screening. The results showed that Next-Generation Sequencing was a breakthrough technology in detecting () gene mutations because of its efficacy and affordability. Other technologies are also being applied now for mutation detection. The most prominent associations of gene mutations were age, heredity, and family history. Furthermore, mutations of could improve survival rate and overall survival. There is no sufficient study available to conclude a systematic analysis for the expression of gene in OC.
EXPERT OPINION
Research will continue to develop more diagnostic techniques based on the expression and mutation of genes for OC in the near future.
Topics: Humans; Female; Genetic Predisposition to Disease; Mutation; Genes, BRCA1; Ovarian Neoplasms; High-Throughput Nucleotide Sequencing; Breast Neoplasms; BRCA1 Protein; BRCA2 Protein
PubMed: 36634123
DOI: 10.1080/14737159.2023.2168190 -
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 -
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 -
Diagnostic Microbiology and Infectious... Jan 2023Plasma cell-free metagenomic next-generation sequencing (cf-mNGS) is a non-invasive method that may be able to identify thousands of pathogens through a hypothesis-free... (Meta-Analysis)
Meta-Analysis
Plasma cell-free metagenomic next-generation sequencing (cf-mNGS) is a non-invasive method that may be able to identify thousands of pathogens through a hypothesis-free approach. There is a lack of consensus on how this test compares to conventional microbiologic testing. We conducted a systematic review and meta-analysis of published studies evaluating the accuracy of plasma cf-mNGS in hospitalized patients and present pooled estimates of the positive (PPA) and negative percent agreement (NPA) compared to a composite reference standard that included all conventional microbiological testing and clinical history as assessed by an adjudication panel or clinical treatment team. Five retrospective studies (n = 552) were included. The majority of the patients (56%-88%) were immunocompromised. The pooled PPA was 67% (95% CI, 54%-81%) and the pooled NPA was 70% (95% CI, 63%-77%). The pooled diagnostic performance characteristics suggest that cf-mNGS provides limited evidence for ruling in or out the presence of infection as commonly used.
Topics: Humans; High-Throughput Nucleotide Sequencing; Retrospective Studies; Metagenomics; Plasma; Communicable Diseases; Sensitivity and Specificity
PubMed: 36375259
DOI: 10.1016/j.diagmicrobio.2022.115838 -
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