Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1233591 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32621550.fastq.gz | Fastqsanger.gz | |||
| SRR32621551.fastq.gz | Fastqsanger.gz | |||
| SRR32621552.fastq.gz | Fastqsanger.gz | |||
| SRR32621553.fastq.gz | Fastqsanger.gz | |||
| SRR32621554.fastq.gz | Fastqsanger.gz |
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Project description:<p>Deep sequencing allows for a rapid, accurate characterization of microbial DNA and RNA sequences in many types of samples. Deep sequencing (also called next generation sequencing or NGS) is being developed to assist with the diagnosis of a wide variety of infectious diseases. In this study, seven frozen brain samples (n = 7) from deceased subjects with recent encephalitis were investigated. RNA from each sample was extracted, randomly reverse transcribed, and sequenced. The sequence analysis was performed in a blinded fashion and confirmed with pathogen-specific PCR. This analysis successfully identified measles virus sequences in two brain samples and herpes simplex virus type-1 sequences in three brain samples. No pathogen was identified in the other two brain specimens. These results were concordant with pathogen-specific PCR and partially concordant with prior neuropathological examinations, demonstrating that deep sequencing can accurately identify viral infections in frozen brain tissue (<a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0093993">Chan et al., 2014</a>).</p> <p>Data from the primary progressive multiple sclerosis (PPMS) brain specimens (n = 14) and Normal Control brain specimens (n = 14) are also submitted here. All the subjects studied here (encephalitis, PPMS, and controls) were selected from existing collections at the Rocky Mountain and UCLA brain banks. These selections were performed by the directors at the two centers (Dr. Corboy at RM and Nagra at UCLA) based on clinic information provided at the time of collection. All the specimens are from deidentified deceased individuals. The submitting investigators have no identifying information on any of these subjects. To avoid confusion, the dbGaP Subject IDs are identical to the brain bank identifying numbers.</p>
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Project description:We have previously developed the use of genetically engineered herpes simplex virus type 1 ("G207") for the experimental treatment of malignant glioma (PMID: 18957964). We demonstrated that G207 propagates in and kills nervous system tumor cells with little to no evidence of viral encephalitis. Here, six adult patients with recurrent glioblastoma were recruited onto a phase Ib clinical trial to test G207 safety and efficacy in anti-tumor response. We obtained resected tumor tissue before and after (within 2-5 days) inoculation with G207. RNA was extracted from all tissues and subject to library preparation for RNA sequencing on Illumina instrumentation.
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Project description:Heterozygous SNORA31 mutations in patients with herpes simplex encephalitis
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Project description:Background: The diagnosis and monitoring of Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis typically rely on clinical manifestations and the detecting of anti-NMDAR antibodies. However, several studies have found that anti-NMDAR IgG in serum is not entirely specific and can be detected in about 3% of healthy individuals. Objective: To identify novel biomarkers that can accurately monitor the severity of anti-NMDAR encephalitis. Methods: We enrolled 9 patients with anti-NMDAR encephalitis and categorized them into an acute-phase group and a stable-phase group based on the duration of illness and disease severity. The clinical severity of the patients was assessed using the modified Rankin Scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE). Then, we isolated exosomal miRNAs from plasma samples and analysed the differentially expressed miRNAs through next-generation sequencing. The sequencing results were validated using RT-qPCR. Furthermore, we conducted correlation analyses between miRNAs and clinical severity. Finally, we performed the functional pathways analysis to explore the underlying mechanisms in anti-NMDAR encephalitis. Results: We have found that exosomal miR-432-5p, miR-4433b-5p and miR-599 exhibited significant differences between patients with anti-NMDAR encephalitis and healthy controls, as well as at different stages of the disease. The expressions of miR-432-5p and miR-4433b-5p were negatively correlated with both the mRS and the CASE. We further identified that the pathways involved in rhythmic processes and neuroinflammation, as well as glutamatergic signaling, play significant roles in the pathogenesis of anti-NMDAR encephalitis. Conclusions: Our research indicates that exosomal miR-432-5p, miR-4433b-5p and miR-599 were highly correlated with the severity of anti-NMDAR encephalitis and can serve as potential biomarkers for disease monitoring. We further identified the pathways play significant roles in anti-NMDAR encephalitis. By modulating the functions of these crucial pathways, we can potentially uncover novel therapeutic targets and improve patient outcomes.
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Project description:We have previously developed the use of genetically engineered herpes simplex virus type 1 (G207) for the experimental treatment of malignant glioma (PMID: 18957964). We demonstrated that G207 propagates in and kills nervous system tumor cells with little to no evidence of viral encephalitis. Here, six adult patients with recurrent glioblastoma were recruited onto a phase 1b clinical trial to test safety and efficacy of G207 in anti-tumor response. We obtained resected tumor tissue before and after (within 2-5 days) inoculation with G207. RNA was extracted from all tissues and subject to gene expression profiling using NanoString Pancancer Immune panel. Our data indicate in the post-G207 samples that interferon immune response and the subsequent recruitment of an adaptive immune response strongly associated with overall survival after inoculation with oncolytic virus G207 in patients with recurrent malignant glioma.
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