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Frontiers in Pediatrics 2023Pediatric and neonatal sepsis is one of the main causes of mortality and morbidity in these age groups. Accurate and early etiological identification is essential for... (Review)
Review
INTRODUCTION
Pediatric and neonatal sepsis is one of the main causes of mortality and morbidity in these age groups. Accurate and early etiological identification is essential for guiding antibiotic treatment, improving survival, and reducing complications and sequelae. Currently, the identification is based on culture-dependent methods, which has many limitations for its use in clinical practice, and obtaining its results is delayed. Next-generation sequencing enables rapid, accurate, and unbiased identification of multiple microorganisms in biological samples at the same time. The objective of this study was to characterize the etiology of neonatal and pediatric sepsis by metagenomic techniques.
METHODS
A systematic review of the literature was carried out using the PRISMA-2020 guide. Observational, descriptive, and case report studies on pediatric patients were included, with a diagnostic evaluation by clinical criteria of sepsis based on the systemic inflammatory response, in sterile and non-sterile biofluid samples. The risk of bias assessment of the observational studies was carried out with the STROBE-metagenomics instrument and the CARE checklist for case reports.
RESULTS AND DISCUSSION
Five studies with a total of 462 patients were included. Due to the data obtained from the studies, it was not possible to perform a quantitative synthesis (meta-analysis). Based on the data from the included studies, the result identified that mNGS improves the etiological identification in neonatal and pediatric sepsis, especially in the context of negative cultures and in the identification of unusual microorganisms (bacteria that are difficult to grow in culture, viruses, fungi, and parasites). The number of investigations is currently limited, and the studies are at high risk of bias. Further research using this technology would have the potential to improve the rational use of antibiotics.
PubMed: 37063664
DOI: 10.3389/fped.2023.1011723 -
Viruses Mar 2021Plant viral diseases are the foremost threat to sustainable agriculture, leading to several billion dollars in losses every year. Many viruses infecting several crops... (Review)
Review
Plant viral diseases are the foremost threat to sustainable agriculture, leading to several billion dollars in losses every year. Many viruses infecting several crops have been described in the literature; however, new infectious viruses are emerging frequently through outbreaks. For the effective treatment and prevention of viral diseases, there is great demand for new techniques that can provide accurate identification on the causative agents. With the advancements in biochemical and molecular biology techniques, several diagnostic methods with improved sensitivity and specificity for the detection of prevalent and/or unknown plant viruses are being continuously developed. Currently, serological and nucleic acid methods are the most widely used for plant viral diagnosis. Nucleic acid-based techniques that amplify target DNA/RNA have been evolved with many variants. However, there is growing interest in developing techniques that can be based in real-time and thus facilitate in-field diagnosis. Next-generation sequencing (NGS)-based innovative methods have shown great potential to detect multiple viruses simultaneously; however, such techniques are in the preliminary stages in plant viral disease diagnostics. This review discusses the recent progress in the use of NGS-based techniques for the detection, diagnosis, and identification of plant viral diseases. New portable devices and technologies that could provide real-time analyses in a relatively short period of time are prime important for in-field diagnostics. Current development and application of such tools and techniques along with their potential limitations in plant virology are likewise discussed in detail.
Topics: Crops, Agricultural; High-Throughput Nucleotide Sequencing; Plant Diseases; Plant Viruses; Polymerase Chain Reaction; Virus Diseases
PubMed: 33807625
DOI: 10.3390/v13030412 -
BMC Infectious Diseases Jun 2016The outcome of leishmaniasis is an interplay between Leishamania and the host. Identifying contributory host genetic factors is complicated by the variability in... (Review)
Review
BACKGROUND
The outcome of leishmaniasis is an interplay between Leishamania and the host. Identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. Leishmaniasis is caused exclusively by L. donovani in Sri Lanka with localized cutaneous leishmaniasis (LCL) being the predominant form. We report here an association study of human leucocyte antigen (HLA) class I and II genes with LCL in Sri Lanka, the first on HLA associations in cutaneous leishmaniasis in a South Asian population.
METHODS
An existing DNA repository of 200 each of patients and controls was typed for HLA-DQ by PCR-SSP. Next generation sequencing-based typing for HLA-A, HLA-B and HLA-DRB1 alleles was done in a subset of 280 samples. Association tests were performed on 28,489 genotyped and imputed SNPs spanning a region of 1.4 Mb across the HLA genes. To compare our results with similar studies, we carried out a systematic review to document all HLA associations reported to-date for cutaneous and muco-cutaneous leishmaniasis.
RESULTS
DRB1*04 DQB1*02 (P = 0.03; Pc = 0.09), DRB1*07 DQB1*02 (P = 0.03; Pc = 0.09) haplotypes were absent in patients. B*07 (P = 0.007; Pc = 0.13; OR = 0.36; 95 % CI = 0.17-0.77) allele and DRB1*15 DQB1*06 (P = 0.00; Pc < 0.01; OR = 0.3; 95 % CI = 0.2-.0.6) haplotype were over represented in controls and DRB1*15 (P = 0.002; Pc = 0.01) allele was over represented in patients. Two SNPs (rs281864595/rs1050517) in the antigen recognition region of HLA-B, comprised a haplotype more frequent in controls (P = 0.04). The alleles identified by the systematic review to predispose or to protect from cutaneous/mucocutaneous leishmaniasis remained highly heterogeneous in different populations studied.
CONCLUSIONS
Our preliminary findings suggest a role for some class I and class II HLA genes in determining predisposition to LCL in this population which should be corroborated with further studies. The systematic review reiterates this need, as the purported susceptibility or protection gained by certain HLA alleles or haplotypes has rarely been independently verified.
Topics: Adolescent; Adult; Alleles; Asian People; Case-Control Studies; Child; Child, Preschool; Ethnicity; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; HLA-A Antigens; HLA-B Antigens; HLA-DQ beta-Chains; HLA-DRB1 Chains; Haplotypes; High-Throughput Nucleotide Sequencing; Humans; Infant; Infant, Newborn; Leishmaniasis, Cutaneous; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Sri Lanka; Young Adult
PubMed: 27301744
DOI: 10.1186/s12879-016-1626-8 -
Radiology and Oncology Mar 2023Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease's next-generation sequencing (NGS) genomic profiling.
MATERIALS AND METHODS
We conducted a systematic review and meta-analysis of the prevalence of studies that discovered the genes and variants occurring in the less aggressive forms of the thymic epithelial tumors. Studies published before 12 December 2022 were identified through PubMed, Web of Science (WoS), and SCOPUS databases. Two reviewers have searched for the bases and selected the articles for the final analysis, based on well-defined exclusion and inclusion criteria.
RESULTS
Finally, 12 publications were included in the qualitative as well as quantitative analysis. The three genes, , , and , emerged as disease-significant in the observed studies. The Odds Ratio for all three extracted genes (OR = 1.58, CI [1.51, 1.66] p < 0.00001) (OR = 1.36, CI [1.12, 1.65], p < 0.002), and (OR = 1.02, CI [1.00, 1.04], p < 0.001).
CONCLUSIONS
According to obtained data, we noticed that the gene exhibits a significant prevalence in the cohort of observed thymoma patients. Moreover, analyzing published articles NGS has suggested , and genes as the most frequently mutated genes in thymoma that have pathogenic single nucleotide variants (SNV) and Insertion/Deletion (InDel), which contribute to disease development and progression. These variants could be valuable biomarkers and target points specific to thymoma.
Topics: Humans; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; High-Throughput Nucleotide Sequencing; Transcription Factors, TFIII
PubMed: 36942904
DOI: 10.2478/raon-2023-0013 -
Water Research Apr 2021The emergence of next generation sequencing (NGS) is revolutionizing the potential to address complex microbiological challenges in the water industry. NGS technologies... (Review)
Review
The emergence of next generation sequencing (NGS) is revolutionizing the potential to address complex microbiological challenges in the water industry. NGS technologies can provide holistic insight into microbial communities and their functional capacities in water and wastewater systems, thus eliminating the need to develop a new assay for each target organism or gene. However, several barriers have hampered wide-scale adoption of NGS by the water industry, including cost, need for specialized expertise and equipment, challenges with data analysis and interpretation, lack of standardized methods, and the rapid pace of development of new technologies. In this critical review, we provide an overview of the current state of the science of NGS technologies as they apply to water, wastewater, and recycled water. In addition, a systematic literature review was conducted in which we identified over 600 peer-reviewed journal articles on this topic and summarized their contributions to six key areas relevant to the water and wastewater fields: taxonomic classification and pathogen detection, functional and catabolic gene characterization, antimicrobial resistance (AMR) profiling, bacterial toxicity characterization, Cyanobacteria and harmful algal bloom identification, and virus characterization. For each application, we have presented key trends, noteworthy advancements, and proposed future directions. Finally, key needs to advance NGS technologies for broader application in water and wastewater fields are assessed.
Topics: Cyanobacteria; Harmful Algal Bloom; High-Throughput Nucleotide Sequencing; Wastewater; Water
PubMed: 33610927
DOI: 10.1016/j.watres.2021.116907 -
Frontiers in Cellular and Infection... 2023Clinical values of metagenomic next-generation sequencing (mNGS) in patients with severe pneumonia remain controversial. Therefore, we conduct this meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clinical values of metagenomic next-generation sequencing (mNGS) in patients with severe pneumonia remain controversial. Therefore, we conduct this meta-analysis to evaluate the diagnostic performance of mNGS for pathogen detection and its role in the prognosis of severe pneumonia.
METHODS
We systematically searched the literature published in PubMed, Embase, Cochrane Library, Web of Science, Clinical Trials.gov, CNKI, Wanfang Data, and CBM from the inception to the 28th September 2022. Relevant trials comparing mNGS with conventional methods applied to patients with severe pneumonia were included. The primary outcomes of this study were the pathogen-positive rate, the 28-day mortality, and the 90-day mortality; secondary outcomes included the duration of mechanical ventilation, the length of hospital stay, and the length of stay in the ICU.
RESULTS
Totally, 24 publications with 3220 patients met the inclusion criteria and were enrolled in this study. Compared with conventional methods (45.78%, 705/1540), mNGS (80.48%, 1233/1532) significantly increased the positive rate of pathogen detection [ = 6.81, 95% (4.59, 10.11, < 0.001]. The pooled 28-day and 90-day mortality in mNGS group were 15.08% (38/252) and 22.36% (36/161), respectively, which were significantly lower than those in conventional methods group 33.05% (117/354) [ = 0.35, 95% (0.23, 0.55), < 0.001, = 0%] and 43.43%(109/251) [ = 0.34, 95% (0.21, 0.54), < 0.001]. Meanwhile, adjusted treatment based on the results of mNGS shortened the length of hospital stay [MD = -2.76, 95% (- 3.56, - 1.96), P < 0.001] and the length of stay in ICU [ = -4.11, 95% (- 5.35, - 2.87), < 0.001].
CONCLUSION
The pathogen detection positive rate of mNGS was much higher than that of conventional methods. Adjusted treatment based on mNGS results can reduce the 28-day and 90-day mortality of patients with severe pneumonia, and shorten the length of hospital and ICU stay. Therefore, mNGS advised to be applied to severe pneumonia patients as early as possible in addition to conventional methods to improve the prognosis and reduce the length of hospital stay.
Topics: Humans; High-Throughput Nucleotide Sequencing; Hospitals; Metagenome; Metagenomics; Pneumonia; Sensitivity and Specificity
PubMed: 37091676
DOI: 10.3389/fcimb.2023.1106859 -
The Journal of Pathology Jul 2022Precision oncology relies on the identification of targetable molecular alterations in tumor tissues. In many tumor types, a limited set of molecular tests is currently... (Review)
Review
Precision oncology relies on the identification of targetable molecular alterations in tumor tissues. In many tumor types, a limited set of molecular tests is currently part of standard diagnostic workflows. However, universal testing for all targetable alterations, especially rare ones, is limited by the cost and availability of molecular assays. From 2017 to 2021, multiple studies have shown that artificial intelligence (AI) methods can predict the probability of specific genetic alterations directly from conventional hematoxylin and eosin (H&E) tissue slides. Although these methods are currently less accurate than gold standard testing (e.g. immunohistochemistry, polymerase chain reaction or next-generation sequencing), they could be used as pre-screening tools to reduce the workload of genetic analyses. In this systematic literature review, we summarize the state of the art in predicting molecular alterations from H&E using AI. We found that AI methods perform reasonably well across multiple tumor types, although few algorithms have been broadly validated. In addition, we found that genetic alterations in FGFR, IDH, PIK3CA, BRAF, TP53, and DNA repair pathways are predictable from H&E in multiple tumor types, while many other genetic alterations have rarely been investigated or were only poorly predictable. Finally, we discuss the next steps for the implementation of AI-based surrogate tests in diagnostic workflows. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Artificial Intelligence; High-Throughput Nucleotide Sequencing; Humans; Mutation; Neoplasms; Precision Medicine
PubMed: 35342954
DOI: 10.1002/path.5898 -
Human Reproduction (Oxford, England) May 2019Which genes are confidently linked to human monogenic male infertility?
STUDY QUESTION
Which genes are confidently linked to human monogenic male infertility?
SUMMARY ANSWER
Our systematic literature search and clinical validity assessment reveals that a total of 78 genes are currently confidently linked to 92 human male infertility phenotypes.
WHAT IS KNOWN ALREADY
The discovery of novel male infertility genes is rapidly accelerating with the availability of next-generating sequencing methods, but the quality of evidence for gene-disease relationships varies greatly. In order to improve genetic research, diagnostics and counseling, there is a need for an evidence-based overview of the currently known genes.
STUDY DESIGN, SIZE, DURATION
We performed a systematic literature search and evidence assessment for all publications in Pubmed until December 2018 covering genetic causes of male infertility and/or defective male genitourinary development.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Two independent reviewers conducted the literature search and included papers on the monogenic causes of human male infertility and excluded papers on genetic association or risk factors, karyotype anomalies and/or copy number variations affecting multiple genes. Next, the quality and the extent of all evidence supporting selected genes was weighed by a standardized scoring method and used to determine the clinical validity of each gene-disease relationship as expressed by the following six categories: no evidence, limited, moderate, strong, definitive or unable to classify.
MAIN RESULTS AND THE ROLE OF CHANCE
From a total of 23 526 records, we included 1337 publications about monogenic causes of male infertility leading to a list of 521 gene-disease relationships. The clinical validity of these gene-disease relationships varied widely and ranged from definitive (n = 38) to strong (n = 22), moderate (n = 32), limited (n = 93) or no evidence (n = 160). A total of 176 gene-disease relationships could not be classified because our scoring method was not suitable.
LARGE SCALE DATA
Not applicable.
LIMITATIONS, REASONS FOR CAUTION
Our literature search was limited to Pubmed.
WIDER IMPLICATIONS OF THE FINDINGS
The comprehensive overview will aid researchers and clinicians in the field to establish gene lists for diagnostic screening using validated gene-disease criteria and help to identify gaps in our knowledge of male infertility. For future studies, the authors discuss the relevant and important international guidelines regarding research related to gene discovery and provide specific recommendations for the field of male infertility.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by a VICI grant from The Netherlands Organization for Scientific Research (918-15-667 to J.A.V.), the Royal Society, and Wolfson Foundation (WM160091 to J.A.V.) as well as an investigator award in science from the Wellcome Trust (209451 to J.A.V.).
PROSPERO REGISTRATION NUMBER
None.
Topics: Biomarkers; DNA Copy Number Variations; DNA Mutational Analysis; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Infertility, Male; Male; Reproducibility of Results; Exome Sequencing
PubMed: 30865283
DOI: 10.1093/humrep/dez022 -
Clinical Genetics Sep 2014As genetic and genomic studies grow in scale, there are ethical concerns related to the collection and use of genetic information. The emergence of large public... (Review)
Review
As genetic and genomic studies grow in scale, there are ethical concerns related to the collection and use of genetic information. The emergence of large public databases potentially redefine the terms of participation in genetic and genomic research, and suggests the changing application of traditional ethical principles such as privacy or consent. For this study, we wanted to see whether such developments are reflected in the informed consent processes in human genetic and genomic studies. Therefore, we performed a systematic review of the empirical studies that examined informed consent involving large genetic databases in human genetic and genomic studies, grouped the identified issues related to the different stakeholders (including subjects, researchers, and institutional review boards) and discussed the limitations and implications of these findings. Major themes related to the place of bioethical considerations, procured tissues, people involved, process of informed consent and study procedures. Frequently raised issues included confidentiality of participants, documentation of informed consent, public attitudes, future use of participant samples or data, and disclosure of results. Awareness and attention to these bioethical issues as well as assiduousness in managing these concerns in genetic/genomic research would further strengthen and safeguard the rights, safety and well-being of genetic research participants.
Topics: Databases, Genetic; Genome-Wide Association Study; High-Throughput Nucleotide Sequencing; Humans; Informed Consent; Tissue Banks
PubMed: 24646408
DOI: 10.1111/cge.12384 -
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