Pharmacometabolomics Flashcards

1
Q

What are 4 applications of metabolomics?

A
  1. Biomarker discovery
  2. Drug discovery and development
  3. Environmental variation
  4. Genetic variation
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2
Q

What is pharmacometabolomics?

A

Understanding patient’s response to therapy from a metabolism perspective i.e., comparing metabolic signature before and after drug exposure

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3
Q

Go through the biomarker discovery workflow starting at untargeted analysis (4)

A
  1. Untargeted Analysis (Global or Fingerprinting) –>
  2. Identification of a “Signature” between Samples –>
  3. Multivariate Statistical Analysis of Data –>
  4. Selection of Candidate Biomarkers –> Targeted Analysis
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4
Q

Go through the biomarker discovery workflow starting at targeted analysis (6)

A
  1. Targeted Analysis (Profiling) –>
  2. Quantification of a specific set of targets based on a hypothesis or biochemical question –>
  3. Biological understanding of biomarker’s differential expression –>
  4. Biomarker validation (Pre-clinical validation) –>
  5. Clinical validation and utility (Clinical Trials I, II, III) –>
  6. Clinical application and regulatory approval
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5
Q

Metabolomics is characterized by high _______ ____

A

dynamic flux

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6
Q

Investigating the human metabolome has the ultimate goal of providing what?

A

Valuable diagnostic and prognostic biomarkers that can be routinely detected/quantified in typical clinical settings

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7
Q

What is the importance of metabolomics? (2)

A
  1. Changes in metabolites concentrations in response to a stimulus occur within seconds
  2. Changes at the metabolite level often appear in biological fluids before the appearance of clinical symptoms
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8
Q

Two important technologies in metabolomics are?

A
  1. NMR (Nuclear Magnetic Resonance)
  2. Mass Spectrometry
    - Liquid chromatography-mass spectrometry (LC-MS)
    - Gas chromatography-mass spectrometry (GC-MS)
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9
Q

What is the question being addressed in targeted metabolomics?

A

What are the levels of specific metabolites in a sample?

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10
Q

What is the question being addressed in untargeted metabolomics?

A

What is the global metabolomic profile of a sample?

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11
Q

What are the 5 challenges in metabolomics?

A
  1. Diverse classes of low-molecular weight compounds (<1500 Da)
  2. Exist in very wide concentration ranges
  3. Affected by genetic and environmental stimuli
  4. Not specific to a single metabolic pathway
  5. Heterogenous physicochemical properties
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12
Q

What are the advantages of using blood in metabolomics? (2)

A
  1. Easy to collect
  2. Instant reflection of metabolome
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13
Q

What are the advantages of using urine in metabolomics? (3)

A
  1. Non-invasive
  2. Low infection risk to researchers
  3. Normalization techniques available
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14
Q

What are the advantages of using saliva in metabolomics? (1)

A

Non-invasive

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15
Q

What are the advantages of using CSF in metabolomics? (1)

A

Convenient to investigate neurological diseases

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16
Q

What are the advantages of using exhaled breath condensate in metabolomics? (2)

A
  1. Non-invasive
  2. Contains volatile metabolites
17
Q

What are the advantages of using tissues in metabolomics? (1)

A

Real refelction of the diseased organ

18
Q

What are the disadvantages of using blood in metabolomics? (3)

A
  1. Complex
  2. High protein content
  3. Needs extraction
19
Q

What are the disadvantages of using urine in metabolomics? (2)

A
  1. High salt content
  2. Affected by age, gender, day, food
20
Q

What are the disadvantages of using saliva in metabolomics? (2)

A
  1. Low concentration
  2. No established assays
21
Q

What are the disadvantages of using CSF in metabolomics? (2)

A
  1. Invasive
  2. Low volumes
22
Q

What are the disadvantages of using exhaled breath condensate in metabolomics? (3)

A
  1. Low concentration
  2. No normalization techniques
  3. Affected by alcohol, smoking, exercise
23
Q

What are the disadvantages of using tissues in metabolomics? (1)

A

Invasive