Alipanahi B, Delong A, Weirauch MT, Frey BJ. Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning. Nat Biotechnol. 2015 Aug;33(8):831-8.
Knowing the sequence specificities of DNA- and RNA-binding proteins is essential for developing models of the regulatory processes in biological systems and for identifying causal disease variants. In this study, we show that sequence specificities ascertained from experimental data with 'deep learning' techniques, offer a scalable, flexible and unified computational approach for pattern discovery.
Zhou S, Wang Y, Meng Y, Xiao C, Liu Z, Brohawn P, Higgs BW, Jallal B, Jia Q, Qu B, Huang X, Tang Y, Yao Y, Harley JB, Shen N. In Vivo Therapeutic Success of MicroRNA-155 Antagomir in a Mouse Model of Lupus Alveolar Hemorrhage. Arthritis Rheumatol. 2016 Apr;68(4):953-64.
Micro-RNA inhibitors are modified RNA molecules themselves, called antagomirs, hold promise as a new class of therapeutic agents. They are anticipated to have broad applicability, efficacy, and utility. Here we show that a particular antagomer is a very effective treatment in an animal model of a very deadly form of systemic lupus erythematosus.
Liu K, Kurien BT, Zimmerman SL, Kaufman KM, Taft DH, Kottyan LC, Lazaro S, Weaver CA, Ice JA, Adler AJ, Chodosh J, Radfar L, Rasmussen A, Stone DU, Lewis DM, Li S, Koelsch KA, Igoe A, Talsania M, Kumar J, Maier-Moore JS, Harris VM, Gopalakrishnan R, Jonsson R, Lessard JA, Lu X, Gottenberg JE, Anaya JM, Cunninghame-Graham DS, Huang AJ, Brennan MT, Hughes P, Illei GG, Miceli-Richard C, Keystone EC, Bykerk VP, Hirschfield G, Xie G, Ng WF, Nordmark G, Eriksson P, Omdal R, Rhodus NL, Rischmueller M, Rohrer M, Segal BM, Vyse TJ, Wahren-Herlenius M, Witte T, Pons-Estel B, Alarcón-Riquelme ME, Guthridge JM, James JA, Lessard CJ, Kelly JA, Thompson SD, Gaffney PM, Montgomery CG, Edberg JC, Kimberly RP, Alarcón GS, Langefeld CL, Gilkeson GS, Kamen DL, Tsao BP, Joseph McCune W, Salmon JE, Merrill JT, Weisman MH, Wallace DJ, Utset TO, Bottinger EP, Amos CI, Siminovitch KA, Mariette X, Sivils KL, Harley JB, Scofield RH. X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome. Arthritis Rheumatol. 2016 May;68(5):1290-300.
The reasons for female dominance of autoimmune diseases has been a long-standing and unsolved mystery. Here we show, for the first time, that the increased frequency of women who have the 47,XXX genotype are at increased risk for systemic lupus erythematosus and Sjogren’s syndrome, thereby further supporting a gene dose effect of the X chromosome as an explanation for female dominance.
Namjou B, Marsolo K, Lingren T, Ritchie MD, Verma SS, Cobb BL, Perry C, Kitchner TE, Brilliant MH, Peissig PL, Borthwick KM, Williams MS, Grafton J, Jarvik GP, Holm IA, Harley JB. A GWAS Study on Liver Function Test Using eMERGE Network Participants. PLoS One. 2015 Sep 28;10(9):e0138677.
Bahram Namjou, MD, and colleagues used the electronic medical record and pre-existing genotyping results from other studies to show that DNA variants at the UGT1A gene govern the level of bilirubin in the blood, confirming that this is the most important locus for the level of bilirubin in pediatric populations.
Clement CC, Moncrieffe H, Lele A, Janow G, Becerra A, Bauli F, Saad FA, Perino G, Montagna C, Cobelli N, Hardin J, Stern LJ, Ilowite N, Porcelli SA, Santambrogio L. Autoimmune response to transthyretin in juvenile idiopathic arthritis. JCI Insight. 2016 Feb;1(2).
The cause of JIA is, by definition, unknown. This study provides evidence for an autoimmune response to a protein called transthyretin (TTR) in patients with JIA. This was reported in an international online news update as "Protein that triggers JIA identified". This study describes the JIA synovial fluid proteome, degradome and identifies increased post-translational modifications in the JIA inflamed site. This study detected autoantibodies to TTR in JIA patient serum and synovial fluid. Proinflammatory cytokines IFN-g and TNF-a was produced and increased immune cell proliferation occurred in response to TTR.