Serum DNA Motifs Predict Disease and Clinical Status in Multiple Sclerosis Julia Beck, Howard B. Urnovitz, Marina Saresella, Domenico Caputo, Mario Clerici,

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Serum DNA Motifs Predict Disease and Clinical Status in Multiple Sclerosis Julia Beck, Howard B. Urnovitz, Marina Saresella, Domenico Caputo, Mario Clerici, William M. Mitchell, Ekkehard Schütz The Journal of Molecular Diagnostics Volume 12, Issue 3, Pages 312-319 (May 2010) DOI: 10.2353/jmoldx.2010.090170 Copyright © 2010 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

Figure 1 Relative representation of DNA sequences assignable to homo sapiens chromosome 17 as a function of distribution over the chromosome, based on a 0.5-kb window. The green line shows distribution in 50 normal subjects, and the red line represents patients with relapsing MS. The blue horizontal line depicts the border of significance adopted for patients versus normal control subjects, which is equivalent to the mean + 4.6 SD (equals P = 0.01 after Bonferroni correction). The blue box indicates the genomic region linked to MS.4 The Journal of Molecular Diagnostics 2010 12, 312-319DOI: (10.2353/jmoldx.2010.090170) Copyright © 2010 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

Figure 2 MVR index distribution (inset) and resulting ROC curves of chromosome (Hs) and repetitive element (RE) representation as well as intragenic representation in serum DNA from RRMS patients versus normal healthy control serum DNA. A: Representation of Hs and RE in relapsing MS patients versus normal control subjects. B: Representation of Hs and RE in stable MS patients versus normal control subjects. C: Representation of genes in relapsing MS patients versus normal control subjects. D: Representation of genes in stable MS patients versus normal control subjects. Main figures (ROC curves): the black line is the actual ROC curve, the solid red lines indicate the 95% confidence interval (2.5 to 97.5% limits) of the ROC curves, and the dashed line represents a line of no separation (c value = 0.5). Data insets: Red dots depict either relapsing MS or stable MS values, green dots are normal control values; the solid line represents the group median. The Journal of Molecular Diagnostics 2010 12, 312-319DOI: (10.2353/jmoldx.2010.090170) Copyright © 2010 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions