DNA methylation based test for monitoring efficacy of treatment
A DNA methylation-based test for efficiency of treatments is based on a plurality of genes. The test is suitable for monitoring treatment of subjects with neurological diseases, e.g., multiple sclerosis (MS); with cancer, e.g., breast and ovarian cancer, and with other diseases for which methylation of biomarkers differs in the diseased compared to the non-diseased state.
1. A method of diagnosing multiple sclerosis (MS) in a subject, the method comprising
(a) generating a MS methylation profile from a biological sample obtained from the subject, wherein the profile comprises the presence of a plurality of MS biomarker genes; and
(b) classifying the methylation profile as similar to profiles of patients diagnosed clinically as having MS, to diagnose MS in the subject
wherein the frequency of biomarker methylation is used to classify the profile, and a computer algorithm determines a conditional probability of MS based on the profile.
2. The method of claim 1 , applied before a subject has manifested clinical symptoms used to define MS.
3. The method of claim 1 , wherein the methylation profile is determined from a plurality of genes listed in Table 1.
4. The method of claim 1 , wherein generating a MS methylation profile comprises digesting genomic DNA with a methylation-sensitive enzyme, wherein the enzyme specifically digests unmethylated sites and not hemi-methylated sites.
5. The method of claim 1 , wherein the MS biomarker genes are selected from the group consisting of BRCA1, CCND2, DAPK, CDH1, FAS, FHIT, ICAM1, MDG1, MCJ, MUC2, MYF3, CDKN2A, TP73, PAX5, PGK1, PR PROX, RB1, SOCS1 and combinations thereof.
6. The method of claim 4 , wherein the enzyme is selected from the group consisting of AciI, HpyCH4IV, Hin6I, HpaII and combinations thereof.
7. The method of claim 1 , wherein the conditional probability is [P c (g 1 /C)*P c (g 2 /C)* . . . (g k /C) vs. [P c (g 1 /nC)*P c (g 2 /nC)* . . . (g k /nC), wherein C is MS and nC is non-MS.
8. The method of claim 1 , wherein the biomarkers are genomic DNA promotors.