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Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS) Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia Leading Research. Delivering Hope.Open Medicine Foundation® Canada
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RAman SPectrometry Based biomarkER discoveRY for Myalgic Encephalomyelitis (RASPBERRY-ME)

STUDY AIM
The overarching goal of RASPBERRY-ME project is the characterization of the biomolecular signature of Myalgic Encephalomyelitis using Label-free Raman Spectroscopy (RS) and machine learning models.
LEAD INVESTIGATORS
  • Alain Moreau, PhD
  • Mathieu Dehaes, PhD
  • Frédéric Leblond, PhD
UPDATES AND POTENTIAL
  • The Raman measurements for the ME/CFS project are completely done. For the entire dataset, we now have five separate subgroups based on the microRNA classification:
    • Group 1: (T0 = 10, T90 = 10) patients
    • Group 2A: (T0 = 30, T90 = 30) patients
    • Group 2B: (T0 = 30, T90 = 30) patients
    • Group 3: (T0 = 30, T90 = 30) patients
    • Group 4: (T0 = 15, T90 = 15) patients
    • Healthy controls (HC): (T0 = 23, T90 = 23) participants
  • Our preliminary models show our capacity to predict with a relatively high accuracy which plasma samples are linked to M/CFS vs HC group at T90 (after the stress-test) with a ROC curve showing an area under the curve (AUC) of 0.86. Raman profiles of plasma can distinguish between healthy individuals and ME/CFS patients with high accuracy (86%).
  • The data have been sent for machine learning (ML) modeling and optimization including the development of models for each subgroup and predicting disease severity.

STUDY HYPOTHESIS AND DESCRIPTION

Woman researcher working with a computer in a laboratory. Raman spectroscopy is a non-destructive, rapid, and low-cost technique allows the study of the molecular composition of biological fluids like blood, or inside a cell when combined with confocal microscopy. This innovative approach could lead to the development of diagnostic tools to better stratify ME patients and find the underlying causes of different symptoms like post-exertional malaise as well as clinical tools to validate the therapeutic potential of pharmacological treatments to treat, stop or mitigate ME through precision medicine.

We hypothesize that our approach will allow the identification of a biomolecular signature of ME both at baseline and in response to the application of a post-exertional stress challenge. We expect to stratify patients by differentiating severe cases from mild forms of ME. Results from this study will be further combined to ongoing proteomic and metabolomic profiling approaches to better understand the pathophysiology of ME.

Objective

  1. Characterize the biomolecular signature of ME patients and healthy age-matched controls using label-free Raman spectroscopy in plasma samples acquired at baseline and after PEM induction
  2. Determine cellular metabolite alterations between ME patients and age-matched controls using Raman spectroscopy combined with confocal microscopy with peripheral blood mononuclear cells (PBMCs) acquired at baseline and after PEM induction
  3. Develop molecular feature detection and machine-learning models capable to predict PEM response (baseline vs. post stress-test) and the disease (ME vs. control).

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Microvesicles and viral sequencing
Microvesicles are a type of extracellular vesicle that is released from the cell membrane. Vesicles are small, fluid-filled sacs or vacuoles within the body. Sequencing is a technique used to determine the exact sequence of bases (A, C, G, and T) in a DNA (or viral) molecule.
NMR Metabolomics
NMR (Nuclear Magnetic Resonance) is an instrument/tool used to perform metabolic studies, metabolic profiling, and metabolomics in biofluids and tissues for more than 40 years using magnetic fields. There is a very close connection between metabolic measurements and NMR. This connection has flourished because of NMR’s many unique strengths for characterizing complex mixtures’ chemical composition.
Proteomics
The large-scale study of proteins, which are large, complex molecules that are required for structure, function, and regulation of the human body's tissues and organs.
Autoantibodies
Antibodies that react with self-molecules and that occur in healthy individuals and are referred to as natural antibodies or autoantibodies.
Extracellular DNA for viral reactivation and Mitochondrial DNA
exDNA (extracellular DNA), exDNA is often secreted actively and is used to perform several tasks, thereby offering an attractive target or tool for biotechnological, medical, environmental, and general microbiological applications. Viruses are intracellular parasites that rely to a significant extent on the host cell for replication. Viral reactivation occurs when an active replication of the viral genome results in a lytic (degradation of the cell) infection characterized by the release of new progeny (descendant) virus particles.
Immune cell profiling
The immune system has many important regulatory roles in disease development and progression. Given the emergence of effective immune therapies, reliable predictors of response are needed. Immune cell profiling determines response by evaluating immune cell populations from treated and untreated samples. For our purposes, we will evaluate the white blood cell response to the viral infection using a process called “Cytof.”
Leukocyte Genomics
A leukocyte is a colorless cell circulating in the blood and body fluids and is involved in counteracting foreign substances and disease. A genome is all genetic material of an organism. Genomics is a biology field focusing on the structure, function, evolution, mapping, and editing of genomes. Therefore, leukocyte genomics is the study of all genetic material of leukocytes.
Metabolomics
Metabolomics is a way to study metabolism – that is, through measuring amounts of the metabolites (small molecules) produced by our bodies as we convert food into energy and other molecules that our cells need to survive. Metabolomics technology is ‘large-scale,’ meaning that several thousand metabolites can be measured from a single sample of e.g., blood or urine.
Micro RNA
Cells use Micro RNA to control whether a particular gene is making too much, too little or the normal amount of its protein at a particular time.