The Omics Flashcards
what are some classic measures of toxicity?
- Histopathology
- Clinical Chemistry
- Metabolism
- Physiology
- Enzymology
- Electron Microscopy
what is NAMs?
New approach methodologies
what are some NAMs?
- 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
what is the tiered protocol for toxicity testing?
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
what is the future path to reduce in vivo methods and test more compounds?
- use NAMs and develop predictive methods for biological responses
what are in silico approaches for testing?
- Data management
- Bioinformatics
- Quantitative structure activity relationship
- Read across
- Modeling
- Reverse dosimetry
what are in chemico approaches for testing?
- identify reactive compounds
- use of analytical technique
what is interpolation vs extrapolation?
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
how can we used high content imaging to assess phenotype? (what are the steps)
- expose cell cultures to variable amounts of compound
- fluorescent staining
- high-content imaging system
- benchmark analyses
- ToxPi analyses
what are different things you can stain and measure with fluorescent screening?
- Nucleus
- Cell viability
- Lysosomes
- Lipid droplets
- Mitochondria
- Oxidative stress
what is BMD and BMC?
dose or concentration that produces a predetermined change in response rate of an adverse effect
what is BMR?
the predetermined change in response rate used to determine the BMD/BMC
how does benchmark concentration modelling work?
- Concentration-response data (high-content imaging)
- Predefined a level of change (benchmark response =10%)
- Fitting a curve (best-fit model)
- Estimate BMC values
what are limitations of NOAEL?
- 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
what is the advantages of BMD?
- 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
what is ToxPi analyses?
Potency ranking of the chemicals based on overall bioactivities
ToxPi analyses is based on what?
BMC data for 8 phenotypic endpoint
What does the area of each slice in ToxPi represent?
endpoint-specific potency of the chemical
what are the 8 endpoints measured in ToxPi?
- oxidative stress
- calcein intensity
- cytotoxicity
- total area of lipid droplets
- lysotracker red intensity
- number of lysosomes
- active mitochondria
- total mitochondria
what is the goal of the “omics”?
Determine whether gene, RNA, protein, lipid, or
metabolite expression profiles or ”signatures” can serve as markers to predict toxicity
what is the genome?
all genes of an individual organism
what is genomics?
the study of all the genes of a cell or tissue at the DNA level
what is transcriptomics?
the study of all gene transcripts of a cell or tissue (RNA level)
what is epigenomics?
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
what is proteomics?
the study of all of the proteins of a cell or tissue
what is lipodomics?
the study of all lipids in an organelle or a cell
what is metabolomics?
the study of all small chemicals in a cell
