Chris Armstrong's presentation at Open Medicine Foundation's Community Symposium, "Molecular Basis of ME/CFS". Stanford University, August 12, 2017.

1. ME, Metabolism and I
Christopher Armstrong

2. Metabolomics
*Image extracted from lecture by David Wishart from University of Alberta - 2016 Informatics
and Statistics for Metabolomics workshop hosted by the Canadian Bioinformatics Workshops
• Metabolites are small organic molecules
(amino acids, sugars, drugs, etc.)
• Metabolomics is the study of these metabolites
• Metabolism is the reaction paths of these metabolites
required to maintain a living cell or organism

3. Blood, Urine, Faecal Study
Metabolomics analysis

4. Physiological Disorder
Blood Urine Stool
UnannotatedspectraMetabolitequantities

5. Metabolites Blood, Urine, Feces
METABOLITES
ME/CFS non-ME/CFS Median Average ME/CFS non-ME/CFS Median Average
μM μM Fold C Fold C p-value % % Fold C Fold C p-value
Glucose 4893 4010 1.22 1.24 0.011 50.4% 36.9% 1.36 1.29 0.002
Hypoxanthine 16 62 0.25 0.38 0.001 0.1% 0.6% 0.26 0.39 0.003
Phenylalanine 67 82 0.82 0.81 0.001 0.6% 0.7% 0.88 0.87 0.003
Lactate 1434 2637 0.54 0.57 0.006 12.8% 24.2% 0.53 0.61 0.004
Glutamate 149 184 0.81 0.80 0.029 1.4% 1.5% 0.90 0.85 0.036
Aspartate 69 62 1.11 1.08 0.272 0.6% 0.5% 1.20 1.17 0.049
Acetate 33 64 0.52 0.75 0.040 0.3% 0.5% 0.60 0.78 0.105
Formate 22 29 0.78 0.71 0.145 0.2% 0.2% 0.83 0.78 0.607
Proline 190 224 0.85 0.85 0.145 1.8% 2.0% 0.91 0.90 0.607
Alanine 467 514 0.91 0.87 0.145 4.4% 4.7% 0.93 0.94 0.607
Citrulline 76 83 0.92 1.03 0.900 0.7% 0.8% 0.94 1.10 0.607
Creatinine 75 77 0.98 0.87 0.077 0.7% 0.7% 1.00 0.91 0.607
Creatine 30 32 0.96 1.16 0.951 0.3% 0.3% 1.13 1.24 0.607
Citrate 101 100 1.00 1.01 0.707 0.9% 0.9% 0.98 1.08 0.629
Betaine 49 51 0.97 1.04 0.837 0.5% 0.4% 1.18 1.14 0.662
Tyrosine 59 64 0.92 0.88 0.145 0.5% 0.6% 0.95 0.94 0.665
Serine 158 173 0.91 0.98 0.707 1.5% 1.5% 1.01 1.05 0.682
Arginine 161 189 0.85 0.88 0.182 1.4% 1.5% 0.95 0.93 0.686
Threonine 175 192 0.91 0.90 0.079 1.6% 1.6% 0.99 0.96 0.741
Ornithine 129 138 0.93 0.90 0.182 1.2% 1.2% 0.97 0.97 0.748
Histidine 97 102 0.95 0.96 0.360 0.9% 0.9% 1.07 1.03 0.758
Asparagine 96 103 0.93 0.95 0.360 0.9% 0.9% 0.98 1.02 0.808
Glycine 293 313 0.94 0.96 0.683 2.7% 2.7% 1.02 1.03 0.808
Isoleucine 68 75 0.91 0.97 0.367 0.6% 0.6% 0.98 1.02 0.895
Valine 227 228 0.99 0.96 0.343 2.1% 2.1% 1.02 1.02 0.895
Glutamine 656 714 0.92 0.95 0.367 6.0% 5.8% 1.03 1.01 0.895
Lysine 186 202 0.92 0.94 0.182 1.8% 1.8% 0.99 1.00 0.954
Tryptophan 60 62 0.97 0.95 0.247 0.6% 0.6% 1.02 1.01 0.954
ABSOLUTE CONCENTRATION RELATIVE ABUNDANCE
METABOLITES
ME/CFS non-ME/CFS Median Average ME/CFS non-ME/CFS Median Average
μM μM Fold C Fold C p-value % % Fold C Fold C p-value
Pyruvate 61 83 0.73 0.69 0.034 0.2% 0.3% 0.72 0.74 0.001
Serine 991 1669 0.59 0.67 0.034 4.1% 6.0% 0.68 0.75 0.008
Alanine 255 393 0.65 0.65 0.049 1.0% 1.5% 0.68 0.76 0.008
Allantoin 161 150 1.07 1.27 0.168 0.8% 0.4% 1.69 1.67 0.011
Acetate 205 353 0.58 0.56 0.003 0.9% 1.5% 0.60 0.68 0.025
Creatinine 6186 4256 1.45 1.22 0.330 28.0% 21.7% 1.29 1.42 0.025
Formate 135 323 0.42 0.44 0.002 0.6% 1.1% 0.49 0.57 0.026
Valine 53 57 0.92 0.82 0.171 0.2% 0.2% 0.81 0.91 0.026
Hypoxanthine 38 66 0.58 0.77 0.063 0.2% 0.2% 0.72 0.73 0.079
Malonate 641 792 0.81 0.72 0.095 2.8% 3.4% 0.84 0.85 0.136
Isobutyrate 49 82 0.59 0.76 0.051 0.2% 0.2% 0.83 0.77 0.173
Threonine 246 378 0.65 0.75 0.088 1.0% 1.2% 0.85 0.85 0.211
Tryptophan 93 132 0.70 0.70 0.073 0.4% 0.5% 0.84 0.83 0.225
Maltose 22 42 0.53 0.37 0.088 0.1% 0.2% 0.58 0.58 0.287
Fructose 807 1100 0.73 0.85 0.168 3.3% 3.8% 0.88 0.87 0.327
n-Methylhistidine 719 1159 0.62 1.19 0.171 3.4% 3.5% 0.99 1.08 0.387
Mannitol 546 768 0.71 0.55 0.066 2.3% 3.2% 0.73 0.73 0.387
Glucose 365 405 0.90 0.84 0.168 1.7% 1.6% 1.01 0.85 0.387
ABSOLUTE CONCENTRATION RELATIVE ABUNDANCE
Increased in ME/CFS
Decreased in ME/CFS
Significant
BLOOD
URINE
FAECES
7 in 29 metabolites were altered
8 of 30 metabolites were altered
4 of 24 metabolites were altered

6. What do we think is occurring in
these patients?

7. Healthy

8. Low energy

9. AMPK turns on

10. Long-term low energy adaptation

11. Are cellular proteins being used?

12. Key benefits of Metabolomics
• Metabolomics gives us insight into the possible
mechanisms of the disorder.
• Metabolomics gives us possible explanations of
symptoms and components of disorder.
• Metabolomics studies may give insight into the
cause.

13. I is for individual
• Measure how metabolites change in individuals with disorder/symptom severity.
• Collect from patients on their worst days, best days and the days between.
• Trace the changes to determine mechanisms of improvement.
Future Studies

14. Acknowledgements
https://www.melbournebioanalytics.org/