| Journal of Clinical Bioinformatics | |
| Using biomarkers to predict progression from clinically isolated syndrome to multiple sclerosis | |
| Thomas M Aune8  Nancy J Olsen5  Cor L Verweij3  Saskia Vosslamber3  Davit Mrelashvili1  Subramaniam Sriram6  Melodie A Henderson7  Philip S Crooke2  John T Tossberg4  | |
| [1] Department of Neurology, University of South Carolina, Columbia, SC, USA;Department of Mathematics, Vanderbilt University, Nashville, TN, USA;Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands;Research Department, ArthroChip, LLC, Franklin, TN, USA;Department of Medicine, Penn State Hershey Medical Center, Hershey, PA, USA;Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN, USA;Department of Medicine, Vanderbilt University School of Medicine, MCN T3219, 1161 21st Avenue South, Nashville, TN, 37232-2681, USA;Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA | |
| 关键词: Diagnosis; Disease prediction; Multiple sclerosis; Genomics; | |
| Others : 801535 DOI : 10.1186/2043-9113-3-18 |
|
| received in 2013-08-21, accepted in 2013-09-30, 发布年份 2013 | |
PDF
|
|
【 摘 要 】
Background
Detection of brain lesions disseminated in space and time by magnetic resonance imaging remains a cornerstone for the diagnosis of clinically definite multiple sclerosis. We have sought to determine if gene expression biomarkers could contribute to the clinical diagnosis of multiple sclerosis.
Methods
We employed expression levels of 30 genes in blood from 199 subjects with multiple sclerosis, 203 subjects with other neurologic disorders, and 114 healthy control subjects to train ratioscore and support vector machine algorithms. Blood samples were obtained from 46 subjects coincident with clinically isolated syndrome who progressed to clinically definite multiple sclerosis determined by conventional methods. Gene expression levels from these subjects were inputted into ratioscore and support vector machine algorithms to determine if these methods also predicted that these subjects would develop multiple sclerosis. Standard calculations of sensitivity and specificity were employed to determine accuracy of these predictions.
Results
Our results demonstrate that ratioscore and support vector machine methods employing input gene transcript levels in blood can accurately identify subjects with clinically isolated syndrome that will progress to multiple sclerosis.
Conclusions
We conclude these approaches may be useful to predict progression from clinically isolated syndrome to multiple sclerosis.
【 授权许可】
2013 Tossberg et al.; licensee BioMed Central Ltd.
【 预 览 】
| Files | Size | Format | View |
|---|---|---|---|
| 20140708010802804.pdf | 1423KB | ||
| Figure 3. | 124KB | Image | |
| Figure 2. | 162KB | Image | |
| Figure 1. | 47KB | Image |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Swanton JK, Rovira A, Tintore M, Altmann DR, Barkhof F, Filippi M, Huerga E, Miszkiel KA, Plant GT, Polman C, et al.: MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study. Lancet Neurol 2007, 6:664-665.
- [2]Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, et al.: Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald criteria". Ann Neurol 2005, 58:840-846.
- [3]McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, et al.: Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 2001, 50:121-127.
- [4]Awad A, Hemmer B, Hartung HP, Kieseier B, Bennett JL, Stuve O: Analyses of cerebrospinal fluid in the diagnosis and monitoring of multiple sclerosis. J Neuroimmunol 2009, 219:1-7.
- [5]Link H, Huang YM: Oligoclonal bands in multile sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness. J Neuroimmunol 2006, 180:17-28.
- [6]Chiappa KH, Ropper AH: Evoked potentials in clinical medicine (second of two parts). N Engl J Med 1982, 306:1205-1211.
- [7]Chiappa KH, Ropper AH: Evoked potentials in clinical medicine (first of two parts). N Engl J Med 1982, 306:1140-1150.
- [8]O'Riordan JI, Thompson AJ, Kingsley DP, MacManus DG, Kendall BE, Rudge P, McDonald WI, Miller DH: The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up. Brain 1998, Pt 3:495-503.
- [9]Comi G, Martinelli V, Rodegher M, Moiola L, Bajenaru O, Carra A, Elovaara I, Fazekas F, Hartung HP, Hillert J, et al.: Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet 2009, 374:1503-1511.
- [10]Jacobson DL, Gange SJ, Rose NR, Graham NM: Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol 1997, 84:223-243.
- [11]Comi G, Filippi M, Barkhof F, Durelli L, Edan G, Fernandez O, Hartung H, Seeldrayers P, Sorensen PS, Rovaris M, et al.: Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001, 357:1576-1582.
- [12]Koch MW, Mostert JP, de Vries JJ, De Keyser J: Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2007, 68:1163-1164. 1163; author reply
- [13]Kappos L, Polman CH, Freedman MS, Edan G, Hartung HP, Miller DH, Montalban X, Barkhof F, Bauer L, Jakobs P, et al.: Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006, 67:1242-1249.
- [14]Dalton CM, Brex PA, Miszkiel KA, Hickman SJ, MacManus DG, Plant GT, Thompson AJ, Miller DH: Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol 2002, 52:47-53.
- [15]Fossey SC, Vnencak-Jones CL, Olsen NJ, Sriram S, Garrison G, Deng X, Crooke P, Aune TM: Identification of molecular biomarkers for multiple sclerosis. J Mol Diagn 2007, 9:197-204.
- [16]Tossberg JT, Crooke PS, Henderson MA, Sriram S, Mrelashvili D, Chitnis S, Polman C, Vosslamber S, Verweij CL, Olsen NJ, Aune TM: Gene-expression signatures: biomarkers toward diagnosing multiple sclerosis. Genes Immun 2012, 13:146-154.
- [17]Crooke PS, Tossberg JT, Horst SN, Tauscher JL, Henderson MA, Beaulieu DB, Schwartz DA, Olsen NJ, Aune TM: Using gene expression data to identify certain gastro-intestinal diseases. J Clin Bioinformatics 2012, 2:20. BioMed Central Full Text
- [18]Ray S, Britschgi M, Herbert C, Takeda-Uchimura Y, Boxer A, Blennow K, Friedman LF, Galasko DR, Jutel M, Karydas A, et al.: Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med 2007, 13:1359-1362.
- [19]Liu Z, Maas K, Aune TM: Identification of gene expression signatures in autoimmune disease without the influence of familial resemblance. Hum Mol Genet 2006, 15:501-509.
- [20]Maas K, Chan S, Parker J, Slater A, Moore J, Olsen N, Aune TM: Cutting edge: molecular portrait of human autoimmune disease. J Immunol 2002, 169:5-9.
- [21]Maas K, Chen H, Shyr Y, Olsen NJ, Aune T: Shared gene expression profiles in individuals with autoimmune disease and unaffected first-degree relatives of individuals with autoimmune disease. Hum Mol Genet 2005, 14:1305-1314.
- [22]Gandhi KS, McKay FC, Cox M, Riveros C, Armstrong N, Heard RN, Vucic S, Williams DW, Stankovich J, Brown M, et al.: The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis. Hum Mol Genet 2010, 19:2134-2143.
PDF