Epigenetic profile of chromosome conformation signatures underlying multiple sclerosis and its severity
Author(s): ,
J.P Joseph
Affiliations:
Hospital Kuala Lumpur, Kuala Lumpur
,
C.R Lim
Affiliations:
Oxford Biodynamics (M) Sdn. Bhd., Penang, Malaysia
,
J Patel
Affiliations:
Oxford Biodynamics (M) Sdn. Bhd., Penang, Malaysia
,
K Rajandran
Affiliations:
Oxford Biodynamics (M) Sdn. Bhd., Penang, Malaysia
,
N.H Nazri
Affiliations:
Hospital Kuala Lumpur, Kuala Lumpur
,
N Mat Zain
Affiliations:
Hospital Kuala Lumpur, Kuala Lumpur
,
M.H Rafia
Affiliations:
Hospital Kuala Lumpur, Kuala Lumpur
,
E Hunter
Affiliations:
Oxford Biodynamics Limited, Oxford, United Kingdom
,
A Ramadass
Affiliations:
Oxford Biodynamics Limited, Oxford, United Kingdom
,
H Womersley
Affiliations:
Oxford Biodynamics Limited, Oxford, United Kingdom
A Akoulitchev
Affiliations:
Oxford Biodynamics Limited, Oxford, United Kingdom
ECTRIMS Online Library. JOSEPH J. Sep 15, 2016; 146441; P601
JOYCE JOSEPH
JOYCE JOSEPH
Contributions
Abstract

Abstract: P601

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - Biomarkers

Introduction: The variability in the clinical presentation and course of MS poses a challenge to physicians, and limited data are available to guide them in selecting effective therapy for their patients.

Chromosome Conformation signatures (CCSs) define a genome-wide framework of early regulatory controls in integrating environmental cues into the epigenetic and transcriptional machinery. As such, the changes in CCSs are the primary step in a cascade of gene deregulation due to pathology, constituting a highly informative systemic epigenetic biomarkers in a broad spectrum of disease indications.

Objective:

1. To characterise Multiple Sclerosis (MS) patients from healthy individuals, and

2. To differentiate the severity of disease in patients with MS.

Methodology: We have collected 20 5-ml whole blood from healthy and 20 MS patients that have been clinically defined, as suffering from Mild and Severe forms of MS as determined by the Expanded Disability Status Scale, at Department of Neurology, Hospital Kuala Lumpur, Malaysia.

Genomic DNAs were isolated based on EpiSwitch™, a proprietary epigenetic marker discovery platform by Oxford Biodynamics. Twenty-six loci chosen from a screening protocol using EpiSwitch™ microarray, have been tested for the formation of CCS for each sample.

Result: We have segregated the samples into 2 groups, i.e. training (n=26) and testing (n=14). As a result, we have found 5 novel markers that can differentiate MS and healthy individuals at a positive predictive value of 100% and a negative predictive value of 71.43%. Furthermore, 6 novel markers can be employed to grade the severity of MS into mild, intermediate and severe, with the precision (T P/(TP+FP)) at 0.895 for the 3 group-classifier. (TP: True Positive; FP: False Positive).

Conclusion: Although current study needs further validation, CCSs prove to be a powerful tool in assisting physicians with early detection of MS and diagnosis of MS severity by objective means of blood-based biomarkers. This pioneering application of CCS biomarkers to MS will be followed with further validation studies on independent patient cohorts.

Disclosure: JP Joseph: Nothing to disclose

Chun Ren Lim: Employee of Oxford Biodynamics (M) Sdn. Bhd.

Patel Janisha: Employee of Oxford Biodynamics (M) Sdn. Bhd.

Rajandran Kushha: Employee of Oxford Biodynamics (M) Sdn. Bhd.

Nazri NH: Nothing to disclose

N Mat Zain: Nothing to disclose

MH Rafia: Nothing to disclose

Hunter Ewan: Employee of Oxford Biodynamics Limited, UK

Ramadass Aroul: Employee of Oxford Biodynamics Limited, UK

Womersley Howard: Employee of Oxford Biodynamics Limited, UK

Akoulitchev Alexandre: Employee of Oxford Biodynamics Limited, UK

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