Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus

Neuron

Volumn 99, Issue 1, 2018, Pages 64-82.e7

  Readhead, Ben ^a,b   Haure Mirande, Jean Vianney ^a   Funk, Cory C ^c   Richards, Matthew A ^c   Shannon, Paul ^c   Haroutunian, Vahram ^a,d   Sano, Mary ^a,d   Liang, Winnie S ^e,f   Beckmann, Noam D ^a   Price, Nathan D ^c   Reiman, Eric M ^e,f,g,h   Schadt, Eric E ^a,i   Ehrlich, Michelle E ^a   Gandy, Sam ^a,d,j   Dudley, Joel T ^a,b  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b ARIZONA STATE UNIVERSITY   (United States)

^c INSTITUTE FOR SYSTEMS BIOLOGY   (United States)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

^e ARIZONA ALZHEIMER S CONSORTIUM   (United States)

^f TRANSLATIONAL GENOMICS RESEARCH INSTITUTE   (United States)

^g UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^h BANNER ALZHEIMER S INSTITUTE   (United States)

ⁱ Sema4   (United States)

^j NATIONAL FOOTBALL LEAGUE   (United States)

more..

Author keywords

Alzheimer's disease; HHV 6A; HHV 6B; HHV 7; human herpesvirus; integrative genomics; multiscale networks; network biology; Roseolovirus; systems biology

Indexed keywords

AMYLOID PRECURSOR PROTEIN; APBB2 PROTEIN; APPBP2 PROTEIN; BETA SECRETASE 1; BIN1 PROTEIN; CLU PROTEIN; GUANINE QUADRUPLEX; MICRORNA 155; PICALM PROTEIN; PSEN1 PROTEIN; REGULATOR PROTEIN; TRANSCRIPTION FACTOR; TRANSFER RNA; UNCLASSIFIED DRUG; ZINC FINGER PROTEIN; ZINC FINGER PROTEIN C2H2;

AGING; ALZHEIMER DISEASE; AMYLOID PLAQUE; ARTICLE; BRAIN REGION; CLINICAL FEATURE; GENETIC ASSOCIATION; GENETIC MANIPULATION; GENETIC RISK; GENETIC VARIABILITY; GENOMICS; HERPESVIRIDAE; HISTOPATHOLOGY; HUMAN; HUMAN HERPESVIRUS 6; HUMAN HERPESVIRUS 7; MICROBIAL ACTIVITY; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN INDUCTION; PROTEOMICS; QUANTITATIVE TRAIT LOCUS; RNA SYNTHESIS; TRANSCRIPTOMICS; VIRUS CELL INTERACTION;

EID: 85048428753     PISSN: 08966273     EISSN: 10974199     Source Type: Journal    
DOI: 10.1016/j.neuron.2018.05.023     Document Type: Article

References (137)

1. 1000 Genomes Project Consortium, Auton, A., Brooks, L.D., Durbin, R.M., Garrison, E.P., Kang, H.M., Korbel, J.O., Marchini, J.L., McCarthy, S., McVean, G.A., Abecasis, G.R., A global reference for human genetic variation. Nature 526 (2015), 68–74.
2. Agostini, S., Mancuso, R., Baglio, F., Cabinio, M., Hernis, A., Guerini, F.R., Calabrese, E., Nemni, R., Clerici, M., Lack of evidence for a role of HHV-6 in the pathogenesis of Alzheimer's disease. J. Alzheimers Dis. 49 (2016), 229–235.
3. Albright, A.V., Lavi, E., Black, J.B., Goldberg, S., O'Connor, M.J., González-Scarano, F., The effect of human herpesvirus-6 (HHV-6) on cultured human neural cells: oligodendrocytes and microglia. J. Neurovirol. 4 (1998), 486–494.
4. Allen, M., Carrasquillo, M.M., Funk, C., Heavner, B.D., Zou, F., Younkin, C.S., Burgess, J.D., Chai, H.S., Crook, J., Eddy, J.A., et al. Human whole genome genotype and transcriptome data for Alzheimer's and other neurodegenerative diseases. Sci. Data, 3, 2016, 160089.
5. Altschul, S.F., Gish, W., Miller, W., Myers, E.W., Lipman, D.J., Basic local alignment search tool. J. Mol. Biol. 215 (1990), 403–410.
6. Ament, S., Shannon, P., and Richards, M. (2017). TReNA: Fit transcriptional regulatory networks using gene expression, priors, machine learning. R package version 0.99.10.
7. Aran, D., Hu, Z., Butte, A.J., xCell: digitally portraying the tissue cellular heterogeneity landscape. Genome Biol., 18, 2017, 220.
8. Arbuckle, J.H., Medveczky, M.M., Luka, J., Hadley, S.H., Luegmayr, A., Ablashi, D., Lund, T.C., Tolar, J., De Meirleir, K., Montoya, J.G., et al. The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc. Natl. Acad. Sci. USA 107 (2010), 5563–5568.
9. Artusi, S., Perrone, R., Lago, S., Raffa, P., Di Iorio, E., Palù G., Richter, S.N., Visualization of DNA G-quadruplexes in herpes simplex virus 1-infected cells. Nucleic Acids Res. 44 (2016), 10343–10353.
10. Beaudoin, J.D., Perreault, J.P., Exploring mRNA 3′-UTR G-quadruplexes: evidence of roles in both alternative polyadenylation and mRNA shortening. Nucleic Acids Res. 41 (2013), 5898–5911.
11. Benjamini, Y., Hochberg, Y., Controlling the false discovery rate - a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57 (1995), 289–300.
12. Bennett, D.A., Schneider, J.A., Arvanitakis, Z., Wilson, R.S., Overview and findings from the religious orders study. Curr. Alzheimer Res. 9 (2012), 628–645.
13. Bennett, D.A., Schneider, J.A., Buchman, A.S., Barnes, L.L., Boyle, P.A., Wilson, R.S., Overview and findings from the rush Memory and Aging Project. Curr. Alzheimer Res. 9 (2012), 646–663.
14. Bernier, A., Cleret-Buhot, A., Zhang, Y., Goulet, J.P., Monteiro, P., Gosselin, A., DaFonseca, S., Wacleche, V.S., Jenabian, M.A., Routy, J.P., et al. Transcriptional profiling reveals molecular signatures associated with HIV permissiveness in Th1Th17 cells and identifies peroxisome proliferator-activated receptor gamma as an intrinsic negative regulator of viral replication. Retrovirology, 10, 2013, 160.
15. Boyle, A.P., Guinney, J., Crawford, G.E., Furey, T.S., F-Seq: a feature density estimator for high-throughput sequence tags. Bioinformatics 24 (2008), 2537–2538.
16. Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., Del Tredici, K., Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 112 (2006), 389–404.
17. Brister, J.R., Ako-Adjei, D., Bao, Y., Blinkova, O., NCBI viral genomes resource. Nucleic Acids Res. 43 (2015), D571–D577.
18. Caccamo, A., Branca, C., Piras, I.S., Ferreira, E., Huentelman, M.J., Liang, W.S., Readhead, B., Dudley, J.T., Spangenberg, E.E., Green, K.N., et al. Necroptosis activation in Alzheimer's disease. Nat. Neurosci. 20 (2017), 1236–1246.
19. Carbone, I., Lazzarotto, T., Ianni, M., Porcellini, E., Forti, P., Masliah, E., Gabrielli, L., Licastro, F., Herpes virus in Alzheimer's disease: relation to progression of the disease. Neurobiol. Aging 35 (2014), 122–129.
20. Cartharius, K., Frech, K., Grote, K., Klocke, B., Haltmeier, M., Klingenhoff, A., Frisch, M., Bayerlein, M., Werner, T., MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 21 (2005), 2933–2942.
21. Caselli, E., D'Accolti, M., Soffritti, I., Zatelli, M.C., Rossi, R., Degli Uberti, E., Di Luca, D., HHV-6A in vitro infection of thyrocytes and T cells alters the expression of miRNA associated to autoimmune thyroiditis. Virol. J., 14, 2017, 3.
22. Cen, S., Khorchid, A., Javanbakht, H., Gabor, J., Stello, T., Shiba, K., Musier-Forsyth, K., Kleiman, L., Incorporation of lysyl-tRNA synthetase into human immunodeficiency virus type 1. J. Virol. 75 (2001), 5043–5048.
23. Chang, L.K., Chung, J.Y., Hong, Y.R., Ichimura, T., Nakao, M., Liu, S.T., Activation of Sp1-mediated transcription by Rta of Epstein-Barr virus via an interaction with MCAF1. Nucleic Acids Res. 33 (2005), 6528–6539.
24. Chen, Z., Simmons, M.S., Perry, R.T., Wiener, H.W., Harrell, L.E., Go, R.C., Genetic association of neurotrophic tyrosine kinase receptor type 2 (NTRK2) With Alzheimer's disease. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 147 (2008), 363–369.
25. Chen, E.Y., Xu, H., Gordonov, S., Lim, M.P., Perkins, M.H., Ma'ayan, A., Expression2Kinases: mRNA profiling linked to multiple upstream regulatory layers. Bioinformatics 28 (2012), 105–111.
26. Cohain, A., Divaraniya, A.A., Zhu, K., Scarpa, J.R., Kasarskis, A., Zhu, J., Chang, R., Dudley, J.T., Schadt, E.E., Exploring the reproducibility of probabilistic causal molecular network models. Pac. Symp. Biocomput. 22 (2017), 120–131.
27. Cox, J., Mann, M., MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26 (2008), 1367–1372.
28. Darmanis, S., Sloan, S.A., Zhang, Y., Enge, M., Caneda, C., Shuer, L.M., Hayden Gephart, M.G., Barres, B.A., Quake, S.R., A survey of human brain transcriptome diversity at the single cell level. Proc. Natl. Acad. Sci. USA 112 (2015), 7285–7290.
29. Dickson, D.W., Crystal, H.A., Mattiace, L.A., Masur, D.M., Blau, A.D., Davies, P., Yen, S.H., Aronson, M.K., Identification of normal and pathological aging in prospectively studied nondemented elderly humans. Neurobiol. Aging 13 (1992), 179–189.
30. Dobin, A., Davis, C.A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., Gingeras, T.R., STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29 (2013), 15–21.
31. Eimer, W.A., Kumar, D.K.V., Shanmugam, N.K.N., Rodriguez, A.S., Mitchell, T., Washicosky, K.J., György, B., Breakefield, X.O., Tanzi, R.E., Moir, R.D., Alzheimer's disease-associated β-amyloid is rapidly seeded by herpesviridae to protect against brain infection. Neuron, 98, 2018, 10.1016/j.neuron.2018.06.030.
32. Epel, E.S., Puterman, E., Lin, J., Blackburn, E.H., Lum, P.Y., Beckmann, N.D., Zhu, J., Lee, E., Gilbert, A., Rissman, R.A., et al. Meditation and vacation effects have an impact on disease-associated molecular phenotypes. Transl. Psychiatry, 6, 2016, e880.
33. Franzén, O., Ermel, R., Cohain, A., Akers, N.K., Di Narzo, A., Talukdar, H.A., Foroughi-Asl, H., Giambartolomei, C., Fullard, J.F., Sukhavasi, K., et al. Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases. Science 353 (2016), 827–830.
34. Garant, J.M., Luce, M.J., Scott, M.S., Perreault, J.P., G4RNA: an RNA G-quadruplex database. Database (Oxford), 2015, 2015, bav059.
35. Gatto, G., Rossi, A., Rossi, D., Kroening, S., Bonatti, S., Mallardo, M., Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway. Nucleic Acids Res. 36 (2008), 6608–6619.
36. Gómez-Isla, T., Price, J.L., McKeel, D.W. Jr., Morris, J.C., Growdon, J.H., Hyman, B.T., Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J. Neurosci. 16 (1996), 4491–4500.
37. Gottwein, E., Mukherjee, N., Sachse, C., Frenzel, C., Majoros, W.H., Chi, J.T., Braich, R., Manoharan, M., Soutschek, J., Ohler, U., Cullen, B.R., A viral microRNA functions as an orthologue of cellular miR-155. Nature 450 (2007), 1096–1099.
38. Grady, S.L., Hwang, J., Vastag, L., Rabinowitz, J.D., Shenk, T., Herpes simplex virus 1 infection activates poly(ADP-ribose) polymerase and triggers the degradation of poly(ADP-ribose) glycohydrolase. J. Virol. 86 (2012), 8259–8268.
39. Gusmao, E.G., Allhoff, M., Zenke, M., Costa, I.G., Analysis of computational footprinting methods for DNase sequencing experiments. Nat. Methods 13 (2016), 303–309.
40. Ha, H.C., Juluri, K., Zhou, Y., Leung, S., Hermankova, M., Snyder, S.H., Poly(ADP-ribose) polymerase-1 is required for efficient HIV-1 integration. Proc. Natl. Acad. Sci. USA 98 (2001), 3364–3368.
41. Haroutunian, V., Perl, D.P., Purohit, D.P., Marin, D., Khan, K., Lantz, M., Davis, K.L., Mohs, R.C., Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease. Arch. Neurol. 55 (1998), 1185–1191.
42. Harrich, D., Garcia, J., Wu, F., Mitsuyasu, R., Gonazalez, J., Gaynor, R., Role of SP1-binding domains in in vivo transcriptional regulation of the human immunodeficiency virus type 1 long terminal repeat. J. Virol. 63 (1989), 2585–2591.
43. Hauw, J.J., Daniel, S.E., Dickson, D., Horoupian, D.S., Jellinger, K., Lantos, P.L., McKee, A., Tabaton, M., Litvan, I., Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology 44 (1994), 2015–2019.
44. Howie, B.N., Donnelly, P., Marchini, J., A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet., 5, 2009, e1000529.
45. Howie, B., Marchini, J., Stephens, M., Genotype imputation with thousands of genomes. G3 (Bethesda) 1 (2011), 457–470.
46. Hsu, S.D., Lin, F.M., Wu, W.Y., Liang, C., Huang, W.C., Chan, W.L., Tsai, W.T., Chen, G.Z., Lee, C.J., Chiu, C.M., et al. miRTarBase: a database curates experimentally validated microRNA-target interactions. Nucleic Acids Res. 39 (2011), D163–D169.
47. Huang, Y., Tanimukai, H., Liu, F., Iqbal, K., Grundke-Iqbal, I., Gong, C.X., Elevation of the level and activity of acid ceramidase in Alzheimer's disease brain. Eur. J. Neurosci. 20 (2004), 3489–3497.
48. Hyman, B.T., Van Hoesen, G.W., Damasio, A.R., Barnes, C.L., Alzheimer's disease: cell-specific pathology isolates the hippocampal formation. Science 225 (1984), 1168–1170.
49. Itzhaki, R.F., Herpes simplex virus type 1 and Alzheimer's disease: increasing evidence for a major role of the virus. Front. Aging Neurosci., 6, 2014, 202.
50. Itzhaki, R.F., Lathe, R., Balin, B.J., Ball, M.J., Bearer, E.L., Braak, H., Bullido, M.J., Carter, C., Clerici, M., Cosby, S.L., et al. Microbes and Alzheimer's Disease. J. Alzheimers Dis. 51 (2016), 979–984.
51. Jankowsky, J.L., Fadale, D.J., Anderson, J., Xu, G.M., Gonzales, V., Jenkins, N.A., Copeland, N.G., Lee, M.K., Younkin, L.H., Wagner, S.L., et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum. Mol. Genet. 13 (2004), 159–170.
52. Kaddurah-Daouk, R., Rozen, S., Matson, W., Han, X., Hulette, C.M., Burke, J.R., Doraiswamy, P.M., Welsh-Bohmer, K.A., Metabolomic changes in autopsy-confirmed Alzheimer's disease. Alzheimers Dement. 7 (2011), 309–317.
53. Kaddurah-Daouk, R., Zhu, H., Sharma, S., Bogdanov, M., Rozen, S.G., Matson, W., Oki, N.O., Motsinger-Reif, A.A., Churchill, E., Lei, Z., et al., Pharmacometabolomics Research Network. Alterations in metabolic pathways and networks in Alzheimer's disease. Transl. Psychiatry, 3, 2013, e244.
54. Kersey, P.J., Allen, J.E., Armean, I., Boddu, S., Bolt, B.J., Carvalho-Silva, D., Christensen, M., Davis, P., Falin, L.J., Grabmueller, C., et al. Ensembl Genomes 2016: more genomes, more complexity. Nucleic Acids Res. 44:D1 (2016), D574–D580.
55. Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O'Loughlin, E., Xu, Y., Fanek, Z., et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47 (2017), 566–581 e9.
56. Kumar, D.K., Choi, S.H., Washicosky, K.J., Eimer, W.A., Tucker, S., Ghofrani, J., Lefkowitz, A., McColl, G., Goldstein, L.E., Tanzi, R.E., Moir, R.D., Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer's disease. Sci. Transl. Med., 8, 2016, 340ra72.
57. Lachmann, A., Xu, H., Krishnan, J., Berger, S.I., Mazloom, A.R., Ma'ayan, A., ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 26 (2010), 2438–2444.
58. Lachmann, A., Torre, D., Keenan, A.B., Jagodnik, K.M., Lee, H.J., Wang, L., Silverstein, M.C., Ma'ayan, A., Massive mining of publicly available RNA-seq data from human and mouse. Nat. Commun., 9, 2018, 1366.
59. Lambert, J.C., Ibrahim-Verbaas, C.A., Harold, D., Naj, A.C., Sims, R., Bellenguez, C., DeStafano, A.L., Bis, J.C., Beecham, G.W., Grenier-Boley, B., et al. European Alzheimer's Disease Initiative (EADI) Genetic and Environmental Risk in Alzheimer's Disease Alzheimer's Disease Genetic Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat. Genet. 45 (2013), 1452–1458.
60. Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., Baldwin, J., Devon, K., Dewar, K., Doyle, M., FitzHugh, W., et al., International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409 (2001), 860–921.
61. Langmead, B., Salzberg, S.L., Fast gapped-read alignment with Bowtie 2. Nat. Methods 9 (2012), 357–359.
62. Law, C.W., Chen, Y., Shi, W., Smyth, G.K., voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol., 15, 2014, R29.
63. Lee, S., Wu, M.C., Lin, X., Optimal tests for rare variant effects in sequencing association studies. Biostatistics 13 (2012), 762–775.
64. Li, H., Durbin, R., Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25 (2009), 1754–1760.
65. Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., 1000 Genome Project Data Processing Subgroup. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25 (2009), 2078–2079.
66. Liang, W.S., Dunckley, T., Beach, T.G., Grover, A., Mastroeni, D., Walker, D.G., Caselli, R.J., Kukull, W.A., McKeel, D., Morris, J.C., et al. Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiol. Genomics 28 (2007), 311–322.
67. Liang, W.S., Dunckley, T., Beach, T.G., Grover, A., Mastroeni, D., Ramsey, K., Caselli, R.J., Kukull, W.A., McKeel, D., Morris, J.C., et al. Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: a reference data set. Physiol. Genomics 33 (2008), 240–256.
68. Liang, W.S., Dunckley, T., Beach, T.G., Grover, A., Mastroeni, D., Ramsey, K., Caselli, R.J., Kukull, W.A., McKeel, D., Morris, J.C., et al. Neuronal gene expression in non-demented individuals with intermediate Alzheimer's Disease neuropathology. Neurobiol. Aging 31 (2010), 549–566.
69. Liao, Y., Smyth, G.K., Shi, W., The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res., 41, 2013, e108.
70. Liao, Y., Smyth, G.K., Shi, W., featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30 (2014), 923–930.
71. Lin, W.R., Wozniak, M.A., Cooper, R.J., Wilcock, G.K., Itzhaki, R.F., Herpesviruses in brain and Alzheimer's disease. J. Pathol. 197 (2002), 395–402.
72. Liu, H.P., Lin, W.Y., Wu, B.T., Liu, S.H., Wang, W.F., Tsai, C.H., Lee, C.C., Tsai, F.J., Evaluation of the poly(ADP-ribose) polymerase-1 gene variants in Alzheimer's disease. J. Clin. Lab. Anal. 24 (2010), 182–186.
73. Liu, J.Z., McRae, A.F., Nyholt, D.R., Medland, S.E., Wray, N.R., Brown, K.M., Hayward, N.K., Montgomery, G.W., Visscher, P.M., Martin, N.G., Macgregor, S., AMFS Investigators. A versatile gene-based test for genome-wide association studies. Am. J. Hum. Genet. 87 (2010), 139–145.
74. Lövheim, H., Gilthorpe, J., Adolfsson, R., Nilsson, L.G., Elgh, F., Reactivated herpes simplex infection increases the risk of Alzheimer's disease. Alzheimers Dement. 11 (2015), 593–599.
75. Lövheim, H., Gilthorpe, J., Johansson, A., Eriksson, S., Hallmans, G., Elgh, F., Herpes simplex infection and the risk of Alzheimer's disease: A nested case-control study. Alzheimers Dement. 11 (2015), 587–592.
76. Madeira, C., Lourenco, M.V., Vargas-Lopes, C., Suemoto, C.K., Brandão, C.O., Reis, T., Leite, R.E., Laks, J., Jacob-Filho, W., Pasqualucci, C.A., et al. d-serine levels in Alzheimer's disease: implications for novel biomarker development. Transl. Psychiatry, 5, 2015, e561.
77. Mak, J., Kleiman, L., Primer tRNAs for reverse transcription. J. Virol. 71 (1997), 8087–8095.
78. Marçais, G., Kingsford, C., A fast, lock-free approach for efficient parallel counting of occurrences of k-mers. Bioinformatics 27 (2011), 764–770.
79. Mastroeni, D., Nolz, J., Sekar, S., Delvaux, E., Serrano, G., Cuyugan, L., Liang, W.S., Beach, T.G., Rogers, J., Coleman, P.D., Laser-captured microglia in the Alzheimer's and Parkinson's brain reveal unique regional expression profiles and suggest a potential role for hepatitis B in the Alzheimer's brain. Neurobiol. Aging 63 (2018), 12–21.
80. Mattiussi, S., Tempera, I., Matusali, G., Mearini, G., Lenti, L., Fratarcangeli, S., Mosca, L., D'Erme, M., Mattia, E., Inhibition of Poly(ADP-ribose)polymerase impairs Epstein Barr Virus lytic cycle progression. Infect. Agent. Cancer, 2, 2007, 18.
81. Middleton, P.J., Petric, M., Kozak, M., Rewcastle, N.B., McLachlan, D.R., Herpes-simplex viral genome and senile and presenile dementias of Alzheimer and Pick. Lancet, 1, 1980, 1038.
82. Miller, J.A., Cai, C., Langfelder, P., Geschwind, D.H., Kurian, S.M., Salomon, D.R., Horvath, S., Strategies for aggregating gene expression data: the collapseRows R function. BMC Bioinformatics, 12, 2011, 322.
83. Millstein, J., Zhang, B., Zhu, J., Schadt, E.E., Disentangling molecular relationships with a causal inference test. BMC Genet., 10, 2009, 23.
84. Mirra, S.S., Heyman, A., McKeel, D., Sumi, S.M., Crain, B.J., Brownlee, L.M., Vogel, F.S., Hughes, J.P., van Belle, G., Berg, L., The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41 (1991), 479–486.
85. Mishra, A., Macgregor, S., VEGAS2: Software for More Flexible Gene-Based Testing. Twin Res. Hum. Genet. 18 (2015), 86–91.
86. Mori, Y., Yagi, H., Shimamoto, T., Isegawa, Y., Sunagawa, T., Inagi, R., Kondo, K., Tano, Y., Yamanishi, K., Analysis of human herpesvirus 6 U3 gene, which is a positional homolog of human cytomegalovirus UL 24 gene. Virology 249 (1998), 129–139.
87. Morris, J.C., The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43 (1993), 2412–2414.
88. Murat, P., Zhong, J., Lekieffre, L., Cowieson, N.P., Clancy, J.L., Preiss, T., Balasubramanian, S., Khanna, R., Tellam, J., G-quadruplexes regulate Epstein-Barr virus-encoded nuclear antigen 1 mRNA translation. Nat. Chem. Biol. 10 (2014), 358–364.
89. Murphy, J.V., Yunis, E.J., Encephalopathy following measles infection in children with chronic illness. J. Pediatr. 88 (1976), 937–942.
90. Newman, A.M., Liu, C.L., Green, M.R., Gentles, A.J., Feng, W., Xu, Y., Hoang, C.D., Diehn, M., Alizadeh, A.A., Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12 (2015), 453–457.
91. Nishida, K., Kawasaki, T., Fujie, M., Usami, S., Yamada, T., Aminoacylation of tRNAs encoded by Chlorella virus CVK2. Virology 263 (1999), 220–229.
92. Nixon, R.A., Wegiel, J., Kumar, A., Yu, W.H., Peterhoff, C., Cataldo, A., Cuervo, A.M., Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J. Neuropathol. Exp. Neurol. 64 (2005), 113–122.
93. Nousiainen, L., Sillanpää M., Jiang, M., Thompson, J., Taipale, J., Julkunen, I., Human kinome analysis reveals novel kinases contributing to virus infection and retinoic-acid inducible gene I-induced type I and type III IFN gene expression. Innate Immun. 19 (2013), 516–530.
94. Nygaard, H.B., Targeting Fyn Kinase in Alzheimer's Disease. Biol. Psychiatry 83 (2018), 369–376.
95. Papadopoulou, C., Guilbaud, G., Schiavone, D., Sale, J.E., Nucleotide pool depletion induces G-quadruplex-dependent perturbation of gene expression. Cell Rep. 13 (2015), 2491–2503.
96. Pearl, J., Causality. 2009, Cambridge University Press.
97. Pearl, J.R., Bergey, D.E., Funk, C.C., Basu, B., Oshone, R., Shannon, P., Hood, L., Price, N.D., Colantuoni, C., Ament, S.A., Genome-scale transcriptional regulatory network models of psychiatric and neurodegenerative disorders. bioRxiv, 2017, 10.1101/190959.
98. Piper, J., Elze, M.C., Cauchy, P., Cockerill, P.N., Bonifer, C., Ott, S., Wellington: a novel method for the accurate identification of digital genomic footprints from DNase-seq data. Nucleic Acids Res., 41, 2013, e201.
99. Prusty, B.K., Krohne, G., Rudel, T., Reactivation of chromosomally integrated human herpesvirus-6 by telomeric circle formation. PLoS Genet., 9, 2013, e1004033.
100. Prusty, B.K., Gulve, N., Rasa, S., Murovska, M., Hernandez, P.C., Ablashi, D.V., Possible chromosomal and germline integration of human herpesvirus 7. J. Gen. Virol. 98 (2017), 266–274.
101. Rampelli, S., Soverini, M., Turroni, S., Quercia, S., Biagi, E., Brigidi, P., Candela, M., ViromeScan: a new tool for metagenomic viral community profiling. BMC Genomics, 17, 2016, 165.
102. Readhead, B., Haure-Mirande, J.V., Zhang, B., Haroutunian, V., Gandy, S., Schadt, E.E., Dudley, J.T., Ehrlich, M.E., Molecular systems evaluation of oligomerogenic APP(E693Q) and fibrillogenic APP(KM670/671NL)/PSEN1(Δexon9) mouse models identifies shared features with human Alzheimer's brain molecular pathology. Mol. Psychiatry 21 (2016), 1099–1111.
103. Rhodes, D., Lipps, H.J., G-quadruplexes and their regulatory roles in biology. Nucleic Acids Res. 43 (2015), 8627–8637.
104. Ritchie, M.E., Phipson, B., Wu, D., Hu, Y., Law, C.W., Shi, W., Smyth, G.K., limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res., 43, 2015, e47.
105. Robinson, M.D., McCarthy, D.J., Smyth, G.K., edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26 (2010), 139–140.
106. Rode, A.B., Endoh, T., Sugimoto, N., tRNA shifts the G-quadruplex-hairpin conformational equilibrium in RNA towards the hairpin conformer. Angew. Chem. Int. Ed. Engl. 55 (2016), 14315–14319.
107. Rotmistrovsky, K., and Agarwala, R. (2011). BMTagger: Best Match Tagger for removing human reads from metagenomics datasets. ftp://ftp.ncbi.nlm.nih.gov/pub/agarwala/bmtagger/.
108. Rouillard, A.D., Gundersen, G.W., Fernandez, N.F., Wang, Z., Monteiro, C.D., McDermott, M.G., Ma'ayan, A., The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Database (Oxford), 2016, 2016, 2016.
109. Sang, Y., Tait, A.R., Scott, W.R., Creagh, A.L., Kumar, P., Haynes, C.A., Straus, S.K., Probing the interaction between U24 and the SH3 domain of Fyn tyrosine kinase. Biochemistry 53 (2014), 6092–6102.
110. Scholz, M., Vogel, J.U., Höver, G., Prösch, S., Kotchetkov, R., Cinatl, J., Koch, F., Doerr, H.W., Cinatl, J. Jr., Thrombin induces Sp1-mediated antiviral effects in cytomegalovirus-infected human retinal pigment epithelial cells. Med. Microbiol. Immunol. (Berl.) 193 (2004), 195–203.
111. Shabalin, A.A., Matrix eQTL: ultra fast eQTL analysis via large matrix operations. Bioinformatics 28 (2012), 1353–1358.
112. Shugar, D., Viral and host-cell protein kinases: enticing antiviral targets and relevance of nucleoside, and viral thymidine, kinases. Pharmacol. Ther. 82 (1999), 315–335.
113. Sigurðsson, B., Rida, a chronic encephalitis of sheep: with general remarks on infections which develop slowly and some of their special characteristics. Brit. Vet. J. 110 (1954), 341–344.
114. Sjogren, T., Sjogren, H., Lindgren, A.G., Morbus Alzheimer and morbus Pick; a genetic, clinical and patho-anatomical study. Acta Psychiatr. Neurol. Scand., Suppl. 82 (1952), 1–152.
115. Smyth, G.K., Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol., 3, 2004, e3.
116. Song, J., Lee, J.E., miR-155 is involved in Alzheimer's disease by regulating T lymphocyte function. Front. Aging Neurosci., 7, 2015, 61.
117. Soscia, S.J., Kirby, J.E., Washicosky, K.J., Tucker, S.M., Ingelsson, M., Hyman, B., Burton, M.A., Goldstein, L.E., Duong, S., Tanzi, R.E., Moir, R.D., The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS ONE, 5, 2010, e9505.
118. Sperling, R.A., Aisen, P.S., Beckett, L.A., Bennett, D.A., Craft, S., Fagan, A.M., Iwatsubo, T., Jack, C.R. Jr., Kaye, J., Montine, T.J., et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 7 (2011), 280–292.
119. Su, J.H., Anderson, A.J., Cummings, B.J., Cotman, C.W., Immunohistochemical evidence for apoptosis in Alzheimer's disease. Neuroreport 5 (1994), 2529–2533.
120. Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Pomeroy, S.L., Golub, T.R., Lander, E.S., Mesirov, J.P., Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102 (2005), 15545–15550.
121. Swanson, C.M., Sherer, N.M., Malim, M.H., SRp40 and SRp55 promote the translation of unspliced human immunodeficiency virus type 1 RNA. J. Virol. 84 (2010), 6748–6759.
122. Tanaka-Taya, K., Sashihara, J., Kurahashi, H., Amo, K., Miyagawa, H., Kondo, K., Okada, S., Yamanishi, K., Human herpesvirus 6 (HHV-6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV-6 DNA. J. Med. Virol. 73 (2004), 465–473.
123. Thai, T.H., Calado, D.P., Casola, S., Ansel, K.M., Xiao, C., Xue, Y., Murphy, A., Frendewey, D., Valenzuela, D., Kutok, J.L., et al. Regulation of the germinal center response by microRNA-155. Science 316 (2007), 604–608.
124. Toribara, N.W., Roberton, A.M., Ho, S.B., Kuo, W.L., Gum, E., Hicks, J.W., Gum, J.R. Jr., Byrd, J.C., Siddiki, B., Kim, Y.S., Human gastric mucin. Identification of a unique species by expression cloning. J. Biol. Chem. 268 (1993), 5879–5885.
125. Upton, J.W., Chan, F.K., Staying alive: cell death in antiviral immunity. Mol. Cell 54 (2014), 273–280.
126. Van der Auwera, G.A., Carneiro, M.O., Hartl, C., Poplin, R., Del Angel, G., Levy-Moonshine, A., Jordan, T., Shakir, K., Roazen, D., Thibault, J., et al. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr. Protoc. Bioinformatics 43 (2013), 1–33 33.
127. Vidal, R., Frangione, B., Rostagno, A., Mead, S., Révész, T., Plant, G., Ghiso, J., A stop-codon mutation in the BRI gene associated with familial British dementia. Nature 399 (1999), 776–781.
128. Vidal, R., Revesz, T., Rostagno, A., Kim, E., Holton, J.L., Bek, T., Bojsen-Møller, M., Braendgaard, H., Plant, G., Ghiso, J., Frangione, B., A decamer duplication in the 3′ region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred. Proc. Natl. Acad. Sci. USA 97 (2000), 4920–4925.
129. Westman, G., Blomberg, J., Yun, Z., Lannfelt, L., Ingelsson, M., Eriksson, B.M., Decreased HHV-6 IgG in Alzheimer's disease. Front. Neurol., 8, 2017, 40.
130. Wong, J., Higgins, M., Halliday, G., Garner, B., Amyloid beta selectively modulates neuronal TrkB alternative transcript expression with implications for Alzheimer's disease. Neuroscience 210 (2012), 363–374.
131. Woodbury, M.E., Freilich, R.W., Cheng, C.J., Asai, H., Ikezu, S., Boucher, J.D., Slack, F., Ikezu, T., miR-155 is essential for inflammation-induced hippocampal neurogenic dysfunction. J. Neurosci. 35 (2015), 9764–9781.
132. Wu, B., Pankow, J.S., Sequence kernel association test of multiple continuous phenotypes. Genet. Epidemiol. 40 (2016), 91–100.
133. Yoo, S., Takikawa, S., Geraghty, P., Argmann, C., Campbell, J., Lin, L., Huang, T., Tu, Z., Foronjy, R.F., Spira, A., et al. Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD. PLoS Genet., 11, 2015, e1004898.
134. Zaharia, M., Bolosky, W.J., Curtis, K., Fox, A., Patterson, D., Shenker, S., Stoica, I., Karp, R.M., and Sittler, T. (2011). Faster and more accurate sequence alignment with SNAP. arXiv, arXiv:1111.5572, https://arxiv.org/abs/1111.5572.
135. Zhang, Y., de Bolle, L., Aquaro, S., van Lommel, A., De Clercq, E., Schols, D., Productive infection of primary macrophages with human herpesvirus 7. J. Virol. 75 (2001), 10511–10514.
136. Zhang, B., Gaiteri, C., Bodea, L.G., Wang, Z., McElwee, J., Podtelezhnikov, A.A., Zhang, C., Xie, T., Tran, L., Dobrin, R., et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell 153 (2013), 707–720.
137. Zhao, Y., Yao, Y., Xu, H., Lambeth, L., Smith, L.P., Kgosana, L., Wang, X., Nair, V., A functional MicroRNA-155 ortholog encoded by the oncogenic Marek's disease virus. J. Virol. 83 (2009), 489–492.