Research summary
Metastate Bio's analysis approach is informed by peer-reviewed research across:
- systems biology
- genome-scale metabolic modeling
- human metabolomics research (as a foundation for what to measure and validate)
- pathway-level interpretation of genetic variation
Important clarity: the DNA Metabolic Action Report does not measure metabolites. It interprets genetic variation in pathway context and suggests validation markers that can be measured separately.
Key idea
Metabolism is a network. Individual genetic variants usually have small effects, but multiple variants affecting the same pathway can indicate potential capacity constraints.
Our approach:
- maps genetic variants to metabolic pathways
- evaluates evidence at the system level
- prioritizes a small number of mechanisms
- frames each insight as a testable hypothesis
- recommends validation markers where possible
Selected references
- Orth JD, Thiele I, Palsson BO. What is flux balance analysis? Nature Biotechnology (2010).
- Bordbar A, Monk JM, King ZA, Palsson BO. Constraint-based models predict metabolic and associated cellular functions. Nature Reviews Genetics (2014).
- Johnson CH, Ivanisevic J, Siuzdak G. Metabolomics: beyond biomarkers and towards mechanisms. Nature Reviews Molecular Cell Biology (2016).
- Nicholson JK, Lindon JC, Holmes E. Metabonomics and systems biology: understanding metabolic responses of living systems. Nature Reviews Drug Discovery (2008).