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Epilepsia Jan 2021Clinical genetic sequencing is frequently utilized to diagnose individuals with neurodevelopmental disorders (NDDs). Here we perform a meta-analysis and systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Clinical genetic sequencing is frequently utilized to diagnose individuals with neurodevelopmental disorders (NDDs). Here we perform a meta-analysis and systematic review of the success rate (diagnostic yield) of clinical sequencing through next-generation sequencing (NGS) across NDDs. We compare the genetic testing yield across NDD subtypes and sequencing technology.
METHODS
We performed a systematic review of the PubMed literature until May 2020. We included clinical sequencing studies that utilized NGS in individuals with epilepsy, autism spectrum disorder (ASD), or intellectual disability (ID). Data were extracted, reviewed, and categorized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators performed clinical evaluation and grouping following the International League Against Epilepsy (ILAE) guidelines. Pooled rates of the diagnostic yield and 95% confidence intervals were estimated with a random-effects model.
RESULTS
We identified 103 studies (epilepsy, N = 72; ASD, N = 14; ID, N = 21) across 32,331 individuals. Targeted gene panel sequencing was used in 73, and exome sequencing in 36 cohorts. Given highly selected patient cohorts, the diagnostic yield was 17.1% for ASD, 24% for epilepsy, and 28.2% for ID (23.7% overall). The highest diagnostic yield for epilepsy subtypes was observed in individuals with ID (27.9%) and early onset seizures (36.8%). The diagnostic yield for exome sequencing was higher than for panel sequencing, even though not statistically significant (27.2% vs 22.6%, P = .071). We observed that clinical sequencing studies are performed predominantly in countries with a high Inequality-adjusted Human Development Index (IHDI) (countries with sequencing studies: IHDI median = 0.84, interquartile range [IQR] = 0.09 vs countries without sequencing studies: IHDI median = 0.56, IQR = 0.3). No studies from Africa, India, or Latin America were identified, indicating potential barriers to genetic testing.
SIGNIFICANCE
This meta-analysis and systematic review provides a comprehensive overview of clinical sequencing studies of NDDs and will help guide policymaking and steer decision-making in patient management.
Topics: Age of Onset; Autism Spectrum Disorder; Epilepsy; High-Throughput Nucleotide Sequencing; Humans; Intellectual Disability; Sequence Analysis, DNA; Exome Sequencing
PubMed: 33200402
DOI: 10.1111/epi.16755 -
Orphanet Journal of Rare Diseases Oct 2020Glycogen storage diseases (GSDs) with liver involvement are complex disorders with similar manifestations. Currently, the main diagnostic methods such as tissue... (Review)
Review
BACKGROUND
Glycogen storage diseases (GSDs) with liver involvement are complex disorders with similar manifestations. Currently, the main diagnostic methods such as tissue diagnosis, either histopathology or enzyme assay, are invasive. Meanwhile, GSDs are diseases with significant genetic heterogeneity, and gene-sequencing methods can be more useful. This systematic review aims to review the literature to assess the value of massively parallel sequencing in the diagnosis of GSDs on patients with previously undiagnosed hepatic involvement.
METHODS
Relevant studies identified in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science Core Collection databases up to July 2019 with no time and language restrictions. Publications were included in the review if they analyzed GSDs with hepatic involvement (GSD I, GSD III, GSD IV, GSD VI, GSD IX), using targeted gene sequencing (TGS) or exome sequencing (ES).
RESULTS
Eleven studies were included in this systematic review. ES demonstrated a 93% diagnostic yield. These methods correctly distinguished all types of pathogenic variants. The diagnostic yield of the TGS method was around 79.7%.
CONCLUSIONS
According to our results, TGS analysis can be considered as the first-line diagnostic method with valuable results and ES can be used to diagnose complex cases of GSD with liver involvement. Overall, these molecular methods are considered as accurate diagnostic tools, which expedite correct diagnosis and treatment with significant cost-effectiveness by reducing unnecessary and inaccurate tests.
PROSPERO REGISTRATION
CRD42020139931. Registered 8 January 2020.
Topics: Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Glycogen Storage Disease Type VI; High-Throughput Nucleotide Sequencing; Humans
PubMed: 33054851
DOI: 10.1186/s13023-020-01573-8 -
Blood Advances Jul 2020Mantle cell lymphoma (MCL) is an incurable rare subtype of non-Hodgkin lymphoma and is subject to relapse and therapeutic resistance. Molecular aberrations in MCL affect... (Meta-Analysis)
Meta-Analysis
Mantle cell lymphoma (MCL) is an incurable rare subtype of non-Hodgkin lymphoma and is subject to relapse and therapeutic resistance. Molecular aberrations in MCL affect pathogenesis, prognosis, and therapeutic response. In this systematic review, we searched 3 databases and selected 32 articles that described mutations in MCL patients. We then conducted a meta-analysis using a Bayesian multiregression model to analyze patient-level data in 2127 MCL patients, including prevalence of mutations. In tumor or bone marrow samples taken at diagnosis or baseline, ATM was the most frequently mutated gene (43.5%) followed by TP53 (26.8%), CDKN2A (23.9%), and CCND1 (20.2%). Aberrations were also detected in IGH (38.4%) and MYC (20.8%), primarily through cytogenetic methods. Other common baseline mutations were NSD2 (15.0%), KMT2A (8.9%), S1PR1 (8.6%), and CARD11 (8.5%). Our data also show a change in mutational status from baseline samples to samples at disease progression and present mutations of interest in MCL that should be considered for future analysis. The genes with the highest mutational frequency difference (>5%) are TP53, ATM, KMT2A, MAP3K14, BTK, TRAF2, CHD2, TLR2, ARID2, RIMS2, NOTCH2, TET2, SPEN, NSD2, CARD11, CCND1, SP140, CDKN2A, and S1PR1. These findings provide a summary of the mutational landscape of MCL. The genes with the highest change in mutation frequency should be included in targeted next-generation sequencing panels for future studies. These findings also highlight the need for analysis of serial samples in MCL. Patient-level data of prevalent mutations in MCL provide additional evidence emphasizing molecular variability in advancing precision medicine initiatives in MCL.
Topics: Adult; Bayes Theorem; High-Throughput Nucleotide Sequencing; Humans; Lymphoma, Mantle-Cell; Mutation; Neoplasm Recurrence, Local
PubMed: 32598477
DOI: 10.1182/bloodadvances.2019001350 -
Journal of Gastrointestinal and Liver... Jun 2020The coexistence of RAS and BRAF mutations is extremely rare, occurring in approximately 0.05% of patients with metastatic colorectal cancer (mCRC). Starting from a case...
BACKGROUND AND AIMS
The coexistence of RAS and BRAF mutations is extremely rare, occurring in approximately 0.05% of patients with metastatic colorectal cancer (mCRC). Starting from a case presentation, this review aims to examine the prevalence, clinical, histopathological and molecular features of tumors with concomitant mutations.
METHODS
Case report and systematic review. We performed a systematic literature search in PubMed and EMBASE using the following MeSH terms: "coexistence" OR "concomitant" AND "RAS" AND "BRAF" AND "colorectal cancer" from the inception of the databases onwards.
RESULTS
We present the case of a 53-year-old man diagnosed with metastatic rectal adenocarcinoma with both a KRAS and a BRAF mutation. The review included eleven papers reporting on a total of 30 mCRC cases with concomitant RAS and BRAF mutations. The male/female ratio was 11/5. The average age was 58.5 years. The tumor was located in nine cases on the right colon and in two cases in the left colon. 43.3% of subjects had liver metastases, and 6.6% had lung metastases. Next-generation sequencing (NGS) was used in 36.6% of cases and polymerase chain reaction (PCR) in 16.6% of cases. KRAS mutations were present in 83.3% of patients and NRAS mutations in 16.6% of patients. Survival could be assessed in 10 patients and the median was 21.1 months (about 30% lower than the survival in the general mCRC population).
CONCLUSION
The results of this systematic review suggest the need to design a cohort study (either prospective or retrospective) to better characterize the patients with concomitant RAS and BRAF mutations and to establish the optimal treatment for this rare situation.
Topics: Adenocarcinoma; Antineoplastic Protocols; Colorectal Neoplasms; Female; GTP Phosphohydrolases; High-Throughput Nucleotide Sequencing; Humans; Liver Neoplasms; Lung Neoplasms; Male; Membrane Proteins; Middle Aged; Mutation; Neoplasm Metastasis; Neoplasm Staging; Pharmacogenomic Testing; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Rectal Neoplasms; Rectum; Response Evaluation Criteria in Solid Tumors; Survival Analysis
PubMed: 32530992
DOI: 10.15403/jgld-1003 -
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 -
Cancer Epidemiology, Biomarkers &... Aug 2020The application of next-generation sequencing (NGS) technologies in cancer research has accelerated the discovery of somatic mutations; however, progress in the...
The application of next-generation sequencing (NGS) technologies in cancer research has accelerated the discovery of somatic mutations; however, progress in the identification of germline variation associated with cancer risk is less clear. We conducted a systematic literature review of cancer genetic susceptibility studies that used NGS technologies at an exome/genome-wide scale to obtain a fuller understanding of the research landscape to date and to inform future studies. The variability across studies on methodologies and reporting was considerable. Most studies sequenced few high-risk (mainly European) families, used a candidate analysis approach, and identified potential cancer-related germline variants or genes in a small fraction of the sequenced cancer cases. This review highlights the importance of establishing consensus on standards for the application and reporting of variants filtering strategies. It also describes the progress in the identification of cancer-related germline variation to date. These findings point to the untapped potential in conducting studies with appropriately sized and racially diverse families and populations, combining results across studies and expanding beyond a candidate analysis approach to advance the discovery of genetic variation that accounts for the unexplained cancer heritability.
Topics: Exome; Genetic Predisposition to Disease; Genome-Wide Association Study; High-Throughput Nucleotide Sequencing; Humans
PubMed: 32467344
DOI: 10.1158/1055-9965.EPI-19-1551 -
Journal of Cancer Research and Clinical... Aug 2020To explore whether targeted next generation sequencing (NGS) of liquid biopsy in advanced non-small cell lung cancer (NSCLC) could potentially overcome the innate... (Comparative Study)
Comparative Study
Comparison of liquid-based to tissue-based biopsy analysis by targeted next generation sequencing in advanced non-small cell lung cancer: a comprehensive systematic review.
PURPOSE
To explore whether targeted next generation sequencing (NGS) of liquid biopsy in advanced non-small cell lung cancer (NSCLC) could potentially overcome the innate problems that arise with standard tissue biopsy, like intratumoral heterogeneity and the inability to obtain adequate samples for analysis.
METHODS
The Scopus, Cochrane Library, and MEDLINE (via PubMed) databases were searched for studies with matched tissue and liquid biopsies from advanced NSCLC patients, analyzed with targeted NGS. The number of mutations detected in tissue biopsy only, liquid biopsy only, or both was assessed and the positive percent agreement (PPA) of the two methods was calculated for every clinically relevant gene.
RESULTS
A total of 644 unique relevant articles were retrieved and data were extracted from 38 studies fulfilling the inclusion criteria. The sample size was composed of 2000 mutations tested in matched tissue and liquid biopsies derived from 1141 patients. No studies analyzed circulating tumor cells. The calculated PPA rates were 53.6% (45/84) for ALK, 53.9% (14/26) for BRAF, 56.5% (13/23) for ERBB2, 67.8% (428/631) for EGFR, 64.2% (122/190) for KRAS, 58.6% (17/29) for MET, 54.6% (12/22) for RET, and 53.3% (8/15) for ROS1. We additionally recorded data for 65 genes that are not recommended by current guidelines for mutational testing. An extra category containing results of unspecified genes was added, with a PPA rate of 55.7% (122/219).
CONCLUSION
Despite many advantages, liquid biopsy might be unable to fully substitute its tissue counterpart in detecting clinically relevant mutations in advanced NSCLC patients. However, it may serve as a helpful tool when making therapeutic decisions. More studies are needed to evaluate its role in everyday clinical practice.
Topics: Biopsy; Carcinoma, Non-Small-Cell Lung; Circulating Tumor DNA; DNA Mutational Analysis; High-Throughput Nucleotide Sequencing; Humans; Liquid Biopsy; Lung Neoplasms; Neoplastic Cells, Circulating
PubMed: 32462295
DOI: 10.1007/s00432-020-03267-x -
PloS One 2020The recent decrease in cost and time to sequence and assemble of complete genomes created an increased demand for data storage. As a consequence, several strategies for...
The recent decrease in cost and time to sequence and assemble of complete genomes created an increased demand for data storage. As a consequence, several strategies for assembled biological data compression were created. Vertical compression tools implement strategies that take advantage of the high level of similarity between multiple assembled genomic sequences for better compression results. However, current reviews on vertical compression do not compare the execution flow of each tool, which is constituted by phases of preprocessing, transformation, and data encoding. We performed a systematic literature review to identify and compare existing tools for vertical compression of assembled genomic sequences. The review was centered on PubMed and Scopus, in which 45726 distinct papers were considered. Next, 32 papers were selected according to the following criteria: to present a lossless vertical compression tool; to use the information contained in other sequences for the compression; to be able to manipulate genomic sequences in FASTA format; and no need prior knowledge. Although we extracted performance compression results, they were not compared as the tools did not use a standardized evaluation protocol. Thus, we conclude that there's a lack of definition of an evaluation protocol that must be applied by each tool.
Topics: Algorithms; Data Compression; Genome; Genomics; High-Throughput Nucleotide Sequencing; Humans; Information Storage and Retrieval; Publications; Sequence Analysis, DNA; Software
PubMed: 32453750
DOI: 10.1371/journal.pone.0232942 -
BMC Infectious Diseases May 2020The burden of drug resistant tuberculosis in Africa is largely driven by the emergence and spread of multidrug resistant (MDR) and extensively drug resistant (XDR)...
BACKGROUND
The burden of drug resistant tuberculosis in Africa is largely driven by the emergence and spread of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis strains. MDR-TB is defined as resistance to isoniazid and rifampicin, while XDR-TB is defined as MDR-TB with added resistance to any of the second line injectable drugs and any fluoroquinolone. The highest burden of drug resistant TB is seen in countries further experiencing an HIV epidemic. The molecular mechanisms of drug resistance as well as the evolution of drug resistant TB strains have been widely studied using various genotyping tools. The study aimed to analyse the drug resistant lineages in circulation and transmission dynamics of these lineages in Africa by describing outbreaks, nosocomial transmission and migration. Viewed as a whole, this can give a better insight into the transmission dynamics of drug resistant TB in Africa.
METHODS
A systematic review was performed on peer reviewed original research extracted from PubMed reporting on the lineages associated with drug resistant TB from African countries, and their association with outbreaks, nosocomial transmission and migration. The search terms "Tuberculosis AND drug resistance AND Africa AND (spoligotyping OR molecular epidemiology OR IS6110 OR MIRU OR DNA fingerprinting OR RFLP OR VNTR OR WGS)" were used to identify relevant articles reporting the molecular epidemiology of drug resistant TB in Africa.
RESULTS
Diverse genotypes are associated with drug resistant TB in Africa, with variations in strain predominance within the continent. Lineage 4 predominates across Africa demonstrating the ability of "modern strains" to adapt and spread easily. Most studies under review reported primary drug resistance as the predominant type of transmission. Drug resistant TB strains are associated with community and nosocomial outbreaks involving MDR- and XDR-TB strains. The under-use of molecular epidemiological tools is of concern, resulting in gaps in knowledge of the transmission dynamics of drug resistant TB on the continent.
CONCLUSIONS
Genetic diversity of M. tuberculosis strains has been demonstrated across Africa implying that diverse genotypes are driving the epidemiology of drug resistant TB across the continent.
Topics: Africa; Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Epidemics; Extensively Drug-Resistant Tuberculosis; Genotype; High-Throughput Nucleotide Sequencing; Humans; Molecular Epidemiology; Mycobacterium tuberculosis; Polymorphism, Restriction Fragment Length
PubMed: 32404119
DOI: 10.1186/s12879-020-05031-5 -
Oral Diseases Jul 2021This systematic review was to evaluate the change of oral microbiome based on next-generation sequencing (NGS)-metagenomic analysis following periodontal interventions... (Review)
Review
OBJECTIVES
This systematic review was to evaluate the change of oral microbiome based on next-generation sequencing (NGS)-metagenomic analysis following periodontal interventions among systematically healthy subjects.
MATERIALS AND METHODS
A structured search strategy consisting of "metagenomics" and "oral diseases" was applied to PubMed, EMBASE, and Web of Science to identify effective papers. The included studies were original studies published in English, using metagenomic approach to analyze the effectiveness of periodontal intervention on oral microbiome among systematically healthy human subjects with periodontitis.
RESULTS
A total of 12 papers were included in this review. Due to the heterogeneity of selected study, quantitative analysis was not performed. The findings as to how alpha diversity changed after interventions were not consistent across studies. Six studies illustrated clear separation of microbial composition between dental plaque samples collected before and after intervention using principal coordinates/component analysis. The most commonly detected genera before intervention were Porphyromonas, Treponema, Tannerella, and Prevotella, while Streptococcus and Actinomyces usually increased and became the dominant genera after intervention. Correlation network analysis revealed that after intervention, the topology of network was different compared to the corresponding pre-interventional samples.
CONCLUSION
Existing evidence of metagenomic studies depicts a complex change in oral microbiome after periodontal intervention.
Topics: High-Throughput Nucleotide Sequencing; Humans; Metagenome; Metagenomics; Microbiota; Periodontitis
PubMed: 32390250
DOI: 10.1111/odi.13405