The Omics Flashcards

1
Q

what are some classic measures of toxicity?

A
  • Histopathology
  • Clinical Chemistry
  • Metabolism
  • Physiology
  • Enzymology
  • Electron Microscopy
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2
Q

what is NAMs?

A

New approach methodologies

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3
Q

what are some NAMs?

A
  • information from the exposure of chemicals in the context of hazard assessment
  • in silico approaches
  • in chemico approaches
  • in vitro assays
  • high-throughput screening
  • high-content imaging
  • genomics
  • transcriptomics
  • epigenomics
  • proteomics
  • lipidomics
  • metabolomic
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4
Q

what is the tiered protocol for toxicity testing?

A

Tier1 :computational based assessment
Tier 2: high throughput in vitro and in vivo screening
Tier 3: in vitro whole cell activity assessment
Tier 4: fish and amphibian whole animal assessment
Tier 5: mammalian whole animal assessment
likely safe

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5
Q

what is the future path to reduce in vivo methods and test more compounds?

A
  • use NAMs and develop predictive methods for biological responses
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6
Q

what are in silico approaches for testing?

A
  • Data management
  • Bioinformatics
  • Quantitative structure activity relationship
  • Read across
  • Modeling
  • Reverse dosimetry
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7
Q

what are in chemico approaches for testing?

A
  • identify reactive compounds
  • use of analytical technique
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8
Q

what is interpolation vs extrapolation?

A

interpolation: unknown is between known data so can get an approximate in between data
extrapolation: unknown is beyond the known data, so you use the general trend to predict result

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9
Q

how can we used high content imaging to assess phenotype? (what are the steps)

A
  1. expose cell cultures to variable amounts of compound
  2. fluorescent staining
  3. high-content imaging system
  4. benchmark analyses
  5. ToxPi analyses
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10
Q

what are different things you can stain and measure with fluorescent screening?

A
  • Nucleus
  • Cell viability
  • Lysosomes
  • Lipid droplets
  • Mitochondria
  • Oxidative stress
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11
Q

what is BMD and BMC?

A

dose or concentration that produces a predetermined change in response rate of an adverse effect

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12
Q

what is BMR?

A

the predetermined change in response rate used to determine the BMD/BMC

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13
Q

how does benchmark concentration modelling work?

A
  1. Concentration-response data (high-content imaging)
  2. Predefined a level of change (benchmark response =10%)
  3. Fitting a curve (best-fit model)
  4. Estimate BMC values
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14
Q

what are limitations of NOAEL?

A
  • Highly dependent on dose selection
  • Highly dependent on sample size
  • Dose–response information (e.g., shape of dose–response curve) not taken into account
  • Does not correspond to consistent response levels for comparisons across studies
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15
Q

what is the advantages of BMD?

A
  • Not limited to experimental doses
  • Less dependent on dose spacing
  • Takes into account the shape of the dose–response curve and other related information
  • Corresponds to consistent response level and can be used to compare results across chemicals and studies
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16
Q

what is ToxPi analyses?

A

Potency ranking of the chemicals based on overall bioactivities

17
Q

ToxPi analyses is based on what?

A

BMC data for 8 phenotypic endpoint

18
Q

What does the area of each slice in ToxPi represent?

A

endpoint-specific potency of the chemical

19
Q

what are the 8 endpoints measured in ToxPi?

A
  • oxidative stress
  • calcein intensity
  • cytotoxicity
  • total area of lipid droplets
  • lysotracker red intensity
  • number of lysosomes
  • active mitochondria
  • total mitochondria
20
Q

what is the goal of the “omics”?

A

Determine whether gene, RNA, protein, lipid, or
metabolite expression profiles or ”signatures” can serve as markers to predict toxicity

21
Q

what is the genome?

A

all genes of an individual organism

22
Q

what is genomics?

A

the study of all the genes of a cell or tissue at the DNA level

23
Q

what is transcriptomics?

A

the study of all gene transcripts of a cell or tissue (RNA level)

24
Q

what is epigenomics?

A

the study of all epigenetic modifications,
e.g., reversible modifications on a cell’s DNA or histones that affect gene expression without altering the DNA sequence

25
Q

what is proteomics?

A

the study of all of the proteins of a cell or tissue

26
Q

what is lipodomics?

A

the study of all lipids in an organelle or a cell

27
Q

what is metabolomics?

A

the study of all small chemicals in a cell

28
Q
A