Pharmacometabolomics Flashcards
What are 4 applications of metabolomics?
- Biomarker discovery
- Drug discovery and development
- Environmental variation
- Genetic variation
What is pharmacometabolomics?
Understanding patient’s response to therapy from a metabolism perspective i.e., comparing metabolic signature before and after drug exposure
Go through the biomarker discovery workflow starting at untargeted analysis (4)
- Untargeted Analysis (Global or Fingerprinting) –>
- Identification of a “Signature” between Samples –>
- Multivariate Statistical Analysis of Data –>
- Selection of Candidate Biomarkers –> Targeted Analysis
Go through the biomarker discovery workflow starting at targeted analysis (6)
- Targeted Analysis (Profiling) –>
- Quantification of a specific set of targets based on a hypothesis or biochemical question –>
- Biological understanding of biomarker’s differential expression –>
- Biomarker validation (Pre-clinical validation) –>
- Clinical validation and utility (Clinical Trials I, II, III) –>
- Clinical application and regulatory approval
Metabolomics is characterized by high _______ ____
dynamic flux
Investigating the human metabolome has the ultimate goal of providing what?
Valuable diagnostic and prognostic biomarkers that can be routinely detected/quantified in typical clinical settings
What is the importance of metabolomics? (2)
- Changes in metabolites concentrations in response to a stimulus occur within seconds
- Changes at the metabolite level often appear in biological fluids before the appearance of clinical symptoms
Two important technologies in metabolomics are?
- NMR (Nuclear Magnetic Resonance)
- Mass Spectrometry
- Liquid chromatography-mass spectrometry (LC-MS)
- Gas chromatography-mass spectrometry (GC-MS)
What is the question being addressed in targeted metabolomics?
What are the levels of specific metabolites in a sample?
What is the question being addressed in untargeted metabolomics?
What is the global metabolomic profile of a sample?
What are the 5 challenges in metabolomics?
- Diverse classes of low-molecular weight compounds (<1500 Da)
- Exist in very wide concentration ranges
- Affected by genetic and environmental stimuli
- Not specific to a single metabolic pathway
- Heterogenous physicochemical properties
What are the advantages of using blood in metabolomics? (2)
- Easy to collect
- Instant reflection of metabolome
What are the advantages of using urine in metabolomics? (3)
- Non-invasive
- Low infection risk to researchers
- Normalization techniques available
What are the advantages of using saliva in metabolomics? (1)
Non-invasive
What are the advantages of using CSF in metabolomics? (1)
Convenient to investigate neurological diseases