Next-generation sequencing in neuropathologic diagnosis of infections of the nervous system
نویسندگان
چکیده
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 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 10 patients with neurologic 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 3 patients for whom validation techniques confirmed the pathogens identified by NGS. Although NGS was unable to identify with precision infectious agents in the remaining cases, it contributed to the understanding of neuropathologic processes in 5 others, demonstrating the power of large-scale unbiased sequencing as a novel diagnostic tool. Clinical outcomes were consistent with the findings yielded by NGS on the presence or absence of an infectious pathogenic process in 8 of 10 cases, and were noncontributory in the remaining 2. 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.
منابع مشابه
Strategies and Clinical Applications of Next Generation Sequencing
Abstract DNA sequencing is one of the great valuable techniques in molecular biology, which can be used to detect the sequence of nucleotides in a DNA fragment. The high-throughput sequencing known as Next Generation Sequencing (NGS) revolutionized genomic research and molecular biology; therefore, the whole human genome can be sequenced with a low cost in several days. NGS technology is simi...
متن کاملNext-generation sequencing in neuropathological diagnosis of infections of the nervous system
متن کامل
Strategies and Clinical Applications of Next Generation Sequencing
Abstract DNA sequencing is one of the great valuable techniques in molecular biology, which can be used to detect the sequence of nucleotides in a DNA fragment. The high-throughput sequencing known as Next Generation Sequencing (NGS) revolutionized genomic research and molecular biology; therefore, the whole human genome can be sequenced with a low cost in several days. NGS technology is simi...
متن کاملGenome Wide Association Studies, Next Generation Sequencing and Their Application in Animal Breeding and Genetics: A Review
Recently genetic studies have been revolutionized by next generation sequencing (NGS) technology, and it is expected that the use of this technology will largely eliminate defects in the methods of association studies. The NGS technology is becoming the premier tool in genetics. However, at the moment the use of this method is limited especially in the livestock due to high cost and computation...
متن کاملI-37: Establishing High Resolution Genomic Profiles of Single Cells Using Microarray and Next-Generation Sequencing Technologies
The nature and pace of genome mutation is largely unknown. Standard methods to investigate DNA-mutation rely on arraying or sequencing DNA from a population of cells, hence the genetic composition of individual cells is lost and de novo mutation in cell(s) is concealed within the bulk signal. We developed methods based on (SNP-) arraying and next-generation sequencing of single-cell whole-genom...
متن کامل