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"ME, Metabolism and I" by Chris Armstrong (2017)

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

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"ME, Metabolism and I" by Chris Armstrong (2017)

  1. 1. ME, Metabolism and I Christopher Armstrong
  2. 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. 3. Blood, Urine, Faecal Study Metabolomics analysis
  4. 4. Physiological Disorder Blood Urine Stool UnannotatedspectraMetabolitequantities
  5. 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. 6. What do we think is occurring in these patients?
  7. 7. Healthy
  8. 8. Low energy
  9. 9. AMPK turns on
  10. 10. Long-term low energy adaptation
  11. 11. Are cellular proteins being used?
  12. 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. 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. 14. Acknowledgements https://www.melbournebioanalytics.org/

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