RT Journal Article
SR Electronic
T1 Next-generation sequencing in neuropathological diagnosis of infections of the nervous system
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 039222
DO 10.1101/039222
A1 Steven L. Salzberg
A1 Florian P. Breitwieser
A1 Anupama Kumar
A1 Haiping Hao
A1 Peter Burger
A1 Fausto J. Rodriguez
A1 Michael Lim
A1 Alfredo Quiñones-Hinojosa
A1 Gary L. Gallia
A1 Jeffrey A. Tornheim
A1 Michael T. Melia
A1 Cynthia L. Sears
A1 Carlos A. Pardo
YR 2016
UL http://biorxiv.org/content/early/2016/02/09/039222.abstract
AB 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.