Erratum to: Illuminating uveitis: metagenomic deep sequencing identifies common and rare pathogens.
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ABSTRACT:
SUBMITTER: Doan T
PROVIDER: S-EPMC5118887 | biostudies-literature | 2016 Nov
REPOSITORIES: biostudies-literature
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Erratum to: Illuminating uveitis: metagenomic deep sequencing identifies common and rare pathogens.
Doan Thuy T Wilson Michael R MR Crawford Emily D ED Chow Eric D ED Khan Lillian M LM Knopp Kristeene A KA O'Donovan Brian D BD Xia Dongxiang D Hacker Jill K JK Stewart Jay M JM Gonzales John A JA Acharya Nisha R NR DeRisi Joseph L JL
Genome medicine 20161122 1
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Project description:BackgroundOcular infections remain a major cause of blindness and morbidity worldwide. While prognosis is dependent on the timing and accuracy of diagnosis, the etiology remains elusive in ~50 % of presumed infectious uveitis cases. The objective of this study is to determine if unbiased metagenomic deep sequencing (MDS) can accurately detect pathogens in intraocular fluid samples of patients with uveitis.MethodsThis is a proof-of-concept study, in which intraocular fluid samples were obtained from five subjects with known diagnoses, and one subject with bilateral chronic uveitis without a known etiology. Samples were subjected to MDS, and results were compared with those from conventional diagnostic tests. Pathogens were identified using a rapid computational pipeline to analyze the non-host sequences obtained from MDS.ResultsUnbiased MDS of intraocular fluid produced results concordant with known diagnoses in subjects with (n = 4) and without (n = 1) uveitis. Samples positive for Cryptococcus neoformans, Toxoplasma gondii, and herpes simplex virus 1 as tested by a Clinical Laboratory Improvement Amendments-certified laboratory were correctly identified with MDS. Rubella virus was identified in one case of chronic bilateral idiopathic uveitis. The subject's strain was most closely related to a German rubella virus strain isolated in 1992, one year before he developed a fever and rash while living in Germany. The pattern and the number of viral identified mutations present in the patient's strain were consistent with long-term viral replication in the eye.ConclusionsMDS can identify fungi, parasites, and DNA and RNA viruses in minute volumes of intraocular fluid samples. The identification of chronic intraocular rubella virus infection highlights the eye's role as a long-term pathogen reservoir, which has implications for virus eradication and emerging global epidemics.
| S-EPMC4997733 | biostudies-literature
Project description:BackgroundMaturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. To date, mutations in 11 genes have been frequently associated with this phenotype. In Brazil, few cohorts have been screened for MODY, all using a candidate gene approach, with a high prevalence of undiagnosed cases (MODY-X).MethodsWe conducted a next-generation sequencing target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected, of which 26 had an initial clinical suspicion of MODY-GCK and 76 were non-GCK MODY.ResultsAfter excluding all benign and likely benign variants and variants of uncertain significance, we were able to assign a genetic cause for 12.7% (13/102) of the probands. Three rare MODY subtypes were identified (PDX1/NEUROD1/ABCC8), and eight variants had not been previously described/mapped in genomic databases. Important clinical findings were evidenced in some cases after genetic diagnosis, such as MODY-PDX1/HNF1B.ConclusionA multiloci genetic approach allowed the identification of rare MODY subtypes, reducing the large percentage of MODY-X in Brazilian cases and contributing to a better clinical, therapeutic, and prognostic characterization of these rare phenotypes.
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Project description:We performed nanopore-based metagenomic screening on 885 ticks collected from 6 locations in Mongolia and divided the results into 68 samples: 23 individual samples and 45 pools of 2-12 tick samples each. We detected bacterial and parasitic pathogens Anaplasma ovis, Babesia microti, Coxiella burnetii, Borrelia miyamotoi, Francisella tularensis subsp. holarctica and novicida, Spiroplasma ixodetis, Theileria equi, and Rickettsia spp., including R. raoultii, R. slovaca, and R. canadensis. We identified the viral pathogens Crimean-Congo hemorrhagic fever virus (2.9%), recently described Alongshan virus (ALSV) (2.9%), and Beiji nairovirus (5.8%). We assembled ALSV genomes, and maximum-likelihood analyses revealed clustering with viruses reported in humans and ticks from China. For ALSV, we identified surface glycoprotein markers associated with isolates from Asia viruses hosted by Ixodes persulcatus ticks. We also detected 20 virus species of unknown public health impact, including a near-complete Yanggou tick virus genome. Our findings demonstrate that nanopore sequencing can aid in detecting endemic and emerging tickborne pathogens.
| S-EPMC11559569 | biostudies-literature
Project description:PurposeTo evaluate the advantages and clinical utility of metagenomic sequencing (MGS) in diagnosing infectious uveitis pathogens.MethodsA retrospective study was conducted on 20 infectious uveitis patients (20 eyes) who received treatments at the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to February 2021. Anterior aqueous humor of the patients was collected and analyzed using MGS. Then, pathogenic microorganisms that cause uveitis were identified through bioinformatic analyses based on the sequencing data of MGS. Finally, the pathogens identified by MGS were verified using both enzyme-linked immune sorbent assay (ELISA) and quantitative PCR (qPCR).ResultsMGS was used to detect viral pathogens in four patients, bacterial pathogens in two patients, and viral and bacterial pathogens in one patient. Among these seven subjects, five were verified by either ELISA or qPCR.ConclusionsMGS holds significant value and promising potential in diagnosing infectious uveitis pathogens. However, it cannot completely replace the traditional diagnostic techniques and still needs to be integrated with conventional methods to enhance the sensitivity and specificity of pathogen detection. As a pioneering technology, MGS will advance the field of pathogen diagnosis in infectious uveitis.
| S-EPMC11688260 | biostudies-literature
Project description:Carotid intima-media thickness (cIMT) is a subclinical measure of atherosclerosis with mounting evidence that higher cIMT confers an increased risk of cardiovascular disease. The ryanodine receptor 3 gene (RYR3) has previously been linked to increased cIMT; however, the causal variants have not yet been localized. Therefore, we sequenced 339,480 bp encompassing 104 exons and 2 kb flanking region of the RYR3 gene in 96 HIV-positive white men from the extremes of the distribution of common cIMT from the Fat Redistribution and Metabolic Changes in HIV infection study (FRAM). We identified 2710 confirmed variants (2414 single-nucleotide polymorphisms (SNPs) and 296 insertion/deletions (indels)), with a mean count of 736 SNPs (ranging from 528 to 1032) and 170 indels (ranging from 128 to 214) distributed in each individual. There were 39 variants in the exons and 15 of these were non-synonymous, of which with only 4 were common variants and the remaining 11 were rare variants, one was a novel SNP. We confirmed that the common variant rs2229116 was significantly associated with cIMT in this design (P<7.9 × 10(-9)), and observed seven other significantly associated SNPs (P<10(-8)). These variants including the private non-synonymous SNPs need to be followed up in a larger sample size and also tested with clinical atherosclerotic outcomes.
| S-EPMC6496937 | biostudies-literature
Project description:Introduction. Diagnosis of uveitis is challenging due to the multitude of possible pathogenies. Identifying infectious and non-infectious uveitis is of great clinical significance. Recently, metagenomic next-generation sequencing (mNGS) was used to detect infectious and non-infectious uveitis, but its efficacy has not been widely evaluated.Hypothesis. Compared with routine diagnostic tests (RDTs), mNGS is more effective in identifying infectious and non-infectious uveitis.Aim. To describe the microbiological diagnostic performance of mNGS in detecting infectious and non-infectious uveitis.Methodology. Patients with suspected infectious uveitis of uncertain pathogenesis were tested by mNGS and RDTs. Infectious and non-infectious uveitis were grouped according to the final diagnosis based on comprehensive analysis of the test results and the effect of therapy. The test results were used to assess the performance of mNGS in actual clinical practice.Results. Fifty-eight cases were enrolled in this project, including 32 cases of infectious uveitis and 26 cases of non-infectious uveitis. The sensitivity of mNGS was 96.88%, which was much higher than that of RDTs. The detected pathogenic micro-organisms included bacteria, fungi, viruses, Toxoplasma gondii and Bartonella. Consequently, mNGS showed a high negative predictive value (NPV) of 94.74%, indicating that an mNGS negative should be a true negative result most of the time, but a low positive predictive value (PPV) of 79.49%.Conclusions. mNGS showed extremely high sensitivity but low specificity, which increased the detection rate of infectious uveitis pathogens but might result in false positives. The excellent NPV suggested that the identification of non-infectious uveitis is of considerable clinical importance.
| S-EPMC11633842 | biostudies-literature
Project description:Metabolomics-genome-wide association studies (mGWAS) have uncovered many metabolic quantitative trait loci (mQTLs) influencing human metabolic individuality, though predominantly in European cohorts. By combining whole-exome sequencing with a high-resolution metabolomics profiling for a highly consanguineous Middle Eastern population, we discover 21 common variant and 12 functional rare variant mQTLs, of which 45% are novel altogether. We fine-map 10 common variant mQTLs to new metabolite ratio associations, and 11 common variant mQTLs to putative protein-altering variants. This is the first work to report common and rare variant mQTLs linked to diseases and/or pharmacological targets in a consanguineous Arab cohort, with wide implications for precision medicine in the Middle East.
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Project description: Not available
| S-EPMC5821905 | biostudies-literature
Project description:ObjectiveIdentification of a particular cause of meningoencephalitis can be challenging owing to the myriad bacteria, viruses, fungi, and parasites that can produce overlapping clinical phenotypes, frequently delaying diagnosis and therapy. Metagenomic deep sequencing (MDS) approaches to infectious disease diagnostics are known for their ability to identify unusual or novel viruses and thus are well suited for investigating possible etiologies of meningoencephalitis.MethodsWe present the case of a 74-year-old woman with endophthalmitis followed by meningoencephalitis. MDS of her cerebrospinal fluid (CSF) was performed to identify an infectious agent.ResultsSequences aligning to Balamuthia mandrillaris ribosomal RNA genes were identified in the CSF by MDS. Polymerase chain reaction subsequently confirmed the presence of B. mandrillaris in CSF, brain tissue, and vitreous fluid from the patient's infected eye. B. mandrillaris serology and immunohistochemistry for free-living amoebas on the brain biopsy tissue were positive.InterpretationThe diagnosis was made using MDS after the patient had been hospitalized for several weeks and subjected to costly and invasive testing. MDS is a powerful diagnostic tool with the potential for rapid and unbiased pathogen identification leading to early therapeutic targeting.
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Project description:Here we present the case of adult medulloblastoma with minimal chromosomal rearrangements but Shh expression profile and IDH1 mutation. Data presented here are NanoString analyses of two biopsies of adult patient with a medulloblastoma which was classified as a Shh subtype Analyses were performed on 2 archival specimens of medulloblastoma, WHO Grade IV, seen at the Department of Pathology, Massachusetts General Hospital in 2007.
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