@article{5bf6adb2ebd94b3f916b1342ebcdb52f,
title = "Application of a bioinformatic pipeline to RNA-seq data identifies novel virus-like sequence in human blood",
abstract = "Numerous reports have suggested that infectious agents could play a role in neurodegenerative diseases, but specific etiological agents have not been convincingly demonstrated. To search for candidate agents in an unbiased fashion, we have developed a bioinformatic pipeline that identifies microbial sequences in mammalian RNA-seq data, including sequences with no significant nucleotide similarity hits in GenBank. Effectiveness of the pipeline was tested using publicly available RNA-seq data and in a reconstruction experiment using synthetic data. We then applied this pipeline to a novel RNA-seq dataset generated from a cohort of 120 samples from amyotrophic lateral sclerosis patients and controls, and identified sequences corresponding to known bacteria and viruses, as well as novel virus-like sequences. The presence of these novel virus-like sequences, which were identified in subsets of both patients and controls, were confirmed by quantitative RT-PCR. We believe this pipeline will be a useful tool for the identification of potential etiological agents in the many RNA-seq datasets currently being generated.",
keywords = "ALS, Microbiome, RNA-seq, Transcriptomics, Virome",
author = "Marko Melnick and Patrick Gonzales and LaRocca, {Thomas J.} and Yuping Song and Joanne Wuu and Michael Benatar and Bj{\"o}rn Oskarsson and Leonard Petrucelli and Dowell, {Robin D.} and Link, {Christopher D.} and Mercedes Prudencio",
note = "Funding Information: This work was supported by the NIH (NS063964 to C.L.); the ALS Association (ALSA, to L.P.; WA1096 and 16-IIP-253 to M.P.; and no. 2015 to M.B.); NINDS (R35NS097273 and P01NS084974 to L.P.); the Mayo Clinic Foundation (to L.P.); Neuroscience Focused Research Team Mayo Clinic grant (to M.P.); the Association of Frontotemporal Dementia (AFTD, to L.P.); the Alzheimer{\textquoteright}s Association-AD Strategic Fund (to L.P.); the Muscular Dystrophy Association (MDA no. 172123 to M.B.); the ALS Recovery Fund (to M.B.); Kimmelman Estate (to M.B.); and the Department of Defense (Chem-Bio Diagnostics program Grant HDTRA-1-18-1-0032 to R.D.D.). Funding Information: This work was supported by the NIH (NS063964 to C.L.); the ALS Association (ALSA, to L.P.; WA1096 and 16-IIP-253 to M.P.; and no. 2015 to M.B.); NINDS (R35NS097273 and P01NS084974 to L.P.); the Mayo Clinic Foundation (to L.P.); Neuroscience Focused Research Team Mayo Clinic grant (to M.P.); the Association of Frontotemporal Dementia (AFTD, to L.P.); the Alzheimer's Association-AD Strategic Fund (to L.P.); the Muscular Dystrophy Association (MDA no. 172123 to M.B.); the ALS Recovery Fund (to M.B.); Kimmelman Estate (to M.B.); and the Department of Defense (Chem-Bio Diagnostics program Grant HDTRA-1-18-1-0032 to R.D.D.). Publisher Copyright: {\textcopyright} The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.",
year = "2021",
doi = "10.1093/g3journal/jkab141",
language = "English (US)",
volume = "11",
journal = "G3 (Bethesda, Md.)",
issn = "2160-1836",
publisher = "Genetics Society of America",
number = "9",
}