scholarly journals PATH-40. STANDARDIZED MOLECULAR ANALYSIS OF PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS IN A RESEARCH BASED CLINICAL PRACTICE. AN INTRODUCTION TO THE PRIMARY CNS TUMOR NEXT GENERATION SEQUENCING (NGS) PANEL

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi179-vi180 ◽  
Author(s):  
Christine Siegel ◽  
Terri Armstrong ◽  
Hye-Jung Chung ◽  
Sonja Crandon ◽  
Snehal Patel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Molecular Analysis ◽  
Cns Tumors ◽  
Next Generation ◽  
Cns Tumor ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

scholarly journals Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections

2021 ◽  
Author(s):  
Nanda Ramchandar ◽  
Nicole G Coufal ◽  
Anna S Warden ◽  
Benjamin Briggs ◽  
Toni Schwarz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Usual Care ◽  
Transcriptomic Analysis ◽  
Cns Infection ◽  
Metagenomic Sequencing ◽  
Next Generation ◽  
Cns Infections ◽  
Generation Sequencing

Abstract Background Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management, but also in characterizing prognosis. Usual care testing by culture and PCR is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with CNS infections. Methods We conducted a prospective multi-site study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to one of three tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis. Results We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. mNGS of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours. Conclusion Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.

scholarly journals Next-generation sequencing in neuropathological diagnosis of infections of the nervous system

2016 ◽  
Author(s):  
Steven L. Salzberg ◽  
Florian Breitwieser ◽  
Anupama Kumar ◽  
Haiping Hao ◽  
Peter Burger ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Large Scale ◽  
Infectious Agent ◽  
Next Generation ◽  
Dna And Rna ◽  
Wide Range ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Objective: To determine the feasibility of next-generation sequencing (NGS) microbiome approaches in the diagnosis of infectious disorders in brain or spinal cord biopsies in patients with suspected central nervous system (CNS) infections. Methods: In a prospective-pilot study, we applied NGS in combination with a new computational analysis pipeline to detect the presence of pathogenic microbes in brain or spinal cord biopsies from ten patients with neurological problems indicating possible infection but for whom conventional clinical and microbiology studies yielded negative or inconclusive results. Results: Direct DNA and RNA sequencing of brain tissue biopsies generated 8.3 million to 29.1 million sequence reads per sample, which successfully identified with high confidence the infectious agent in three patients, identified possible pathogens in two more, and helped to understand neuropathological processes in three others, demonstrating the power of large-scale unbiased sequencing as a novel diagnostic tool. Validation techniques confirmed the pathogens identified by NGS in each of the three positive cases. Clinical outcomes were consistent with the findings yielded by NGS on the presence or absence of an infectious pathogenic process in eight of ten cases, and were non-contributory in the remaining two. Conclusions: NGS-guided metagenomic studies of brain, spinal cord or meningeal biopsies offer the possibility for dramatic improvements in our ability to detect (or rule out) a wide range of CNS pathogens, with potential benefits in speed, sensitivity, and cost. NGS-based microbiome approaches present a major new opportunity to investigate the potential role of infectious pathogens in the pathogenesis of neuroinflammatory disorders.

scholarly journals Clinical significance of TP53 variants as possible secondary findings in tumor-only next-generation sequencing

2019 ◽  
Vol 65 (2) ◽  
pp. 125-132
Author(s):  
Yoshihiro Yamamoto ◽  
Masashi Kanai ◽  
Tadayuki Kou ◽  
Aiko Sugiyama ◽  
Eijiro Nakamura ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Informed Consent ◽  
Family History ◽  
Next Generation ◽  
Secondary Findings ◽  
Low Prevalence ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Germline Testing

Abstract In tumor-only next-generation sequencing (NGS), identified variants have the potential to be secondary findings (SFs), but they require verification through additional germline testing. In the present study, 194 patients with advanced cancer who underwent tumor-only NGS between April 2015 and March 2018 were enrolled, and the incidences of possible and true SFs were evaluated. Among them, 120 patients (61.9%) harbored at least one possible SF. TP53 was the most frequent gene in which 97 variants were found in 91 patients (49.5%). Nine patients provided informed consent to undergo additional germline testing, and a total of 14 variants (BRCA1, n = 1; BRCA2, n = 2; PTEN, n = 2; RB1, n = 1; SMAD4, n = 1; STK11, n = 1; TP53, n = 6) were analyzed. Three variants (BRCA1, n = 1; BRCA2, n = 2) were confirmed to be SFs, whereas TP53 variants were confirmed to be somatic variants. To confirm the low prevalence of SFs in TP53, we analyzed 24 patients with TP53 variants who underwent a paired tumor–normal NGS assay. As expected, all TP53 variants were confirmed to be somatic variants. A total of 30 patients were tested for germline variants in TP53, but none of them resulted in true SFs, suggesting the low prevalence of SFs in this gene. Therefore, the significance of additional germline testing for TP53 variants appears to be relatively low in daily clinical practice using a tumor-only NGS assay, unless patients have any relevant medical or family history.

scholarly journals 342. Clinical Utility of a Next Generation Sequencing Test for Pathogen Detection in Pediatric Central Nervous System Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S241-S241
Author(s):  
Nanda Ramchandar ◽  
Jennifer Foley ◽  
Claudia Enriquez ◽  
Stephanie Osborne ◽  
Antonio Arrieta ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Standard Care ◽  
Cns Infection ◽  
Next Generation ◽  
Diagnostic Modality ◽  
Cns Infections ◽  
Pcr Multiplex ◽  
Generation Sequencing

Abstract Background Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management, but also in characterizing prognosis. However, standard care testing by culture, serology, and PCR is often unable to identify a pathogen. We examined use of next generation sequencing (NGS) of cerebrospinal fluid (CSF) in detecting an organism in children with CNS infections. Methods We prospectively enrolled children with CSF pleocytosis and suspected CNS infection admitted to 3 tertiary pediatric hospitals. After standard care testing had been performed, the remaining CSF was submitted for analysis by NGS. Results We enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 24 (34.3%) subjects by any diagnostic modality. NGS of the CSF samples identified a pathogen in 20 (28.6%) subjects. False positive results by NGS were identified in 2 patients. There were no cases in which NGS alone identified a pathogen. In 4 cases, a putative organism was recovered by standard care testing of the CSF, but not by CSF NGS. CSF culture recovered a putative organism in 12 cases (12.1%). A CSF PCR multiplex panel was utilized for 51 subjects. An organism was detected in 15 of these (29.4%). Using a reference composite of standard care testing, we determined the sensitivity and specificity of CSF NGS to be 83.3% (95% CI, 62.6–95.3%) and 91.3% (95% CI, 79.2–97.6%) respectively. Conclusion Sequencing of CSF has the potential to rapidly and comprehensively identify infection with a single test. Further studies are needed to determine the optimal use of NGS for diagnosis of CNS infections. Disclosures All Authors: No reported disclosures

scholarly journals Metagenomic Next-generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Central Nervous System infections in HIV-infected patients

2019 ◽  
Author(s):  
Nai qing Zheng ◽  
Pengle Guo ◽  
Xiejie Chen ◽  
Haolan He ◽  
Yueping Li ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Clinical Diagnosis ◽  
Central Nervous System Infection ◽  
Next Generation ◽  
Central Nervous System Infections ◽  
Cns Infections ◽  
Conventional Methods ◽  
Generation Sequencing

Abstract Background HIV-infected patients have extremely low immunity and various opportunistic infections. Early diagnosis and treatment of these pathogens is critical for patients with HIV infection, especially those with central nervous system (CNS) infections. Metagenomic next generation sequencing (mNGS) has the advantage of identifying a broad range of pathogens and was suggested as a promising tool in the clinical diagnosis for infectious diseases. The clinical application of mNGS in the diagnosis of CNS infections in patients infected with HIV remains inadequately characterized.Methods We retrospectively analyzed data from 22 patients with suspected central nervous system infections who underwent both mNGS and conventional methods including culture, PCR, X-pert/RIF and antigen testing to explored the utility of mNGS in clinical diagnostic microbiology of CNS infections in HIV-infected patients.Results A total of 22 patients participated in the study between June 2018 and May 2019. The consistency of positive percentage of mNGS compared to clinical diagnosis was significantly higher than that of conventional methods (86.36% vs. 45.21%). The proportion of co-infections in mNGS positive samples was significantly higher than that in traditional methods (40.91% vs. 14.39%). Sixteen Extra Pathogens in 14 cases identified by metagenomic NGS only, 6 pathogens affected clinical reasoning and 7 pathogens guided antimicrobial therapy.Conclusions MNGS is a powerful diagnostic method for identifying pathogens in central nervous system infections and provide actionable information in some cases. MNGS technology has positive significance for the diagnosis and clinical treatment of central nervous system infection in HIV-infected patients.

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