Glucose Modelling Flashcards
Model
The complexity of a model is lower than the complexity of the system
A good model represent all features which are relevant for the application
Genome-scale constrained:
Computationally represent metabolites. Can predict fluxed without a lot of info, assume steady state
Machine/Deep Learning:
Massive good quality data needed, lack of interpretation: why is the model doing this? black box, find patterns without human interaction
Dynamic models:
Math, quantify fluxes. Represent our knowledge of the fluxes
Metabolism study
Medication don’t work on all individuals -> tailor treatment
Dynamic modeling
mechanistic: based on mathematical description of biological phenomenon. ex: Glucose-Insulin system
modeled using differential equations, quantitative information on interactions, dynamics and regulation. equations reflect physiological knowledge. Handled by parameters
Minimal model: parsimonious description of the key components of system functionality.
Too simple: response not accurate
Too complex: requires info not available by studies
Glucose regulatory system
Plasma glucose
Paslma Insulin
T2DM
Insulin resistance -> less glucose stored/used in/by organs -> increase glucose in blood
Glucose minimal model
Predict plasma glucose given insulin concentration following an oral glucose dose
Parameters: insulin sensitivity (amount of insulin to be produced to have certain amount of glucose: sensitivity body cell to insulin)
Input: glucose produce by liver and arrive in plasma from gut
output: glucose leave plasma from uptake of periphery and liver
Insulin action: enhance glucose uptake by periphery and inhibit glucose production by liver
Parameter estimation
Interpolation Simulate glucose compute error Fit model to data by changing parameters reduce error
Central dogma
DNA contains instructions for making protein which are copied to RNA and RNA use instruction to make protein.
DNA -> RNA -> Protein
Transcription: DNA to mRNA
Translation: mRNA to protein
Genetic Variation
Genomics
difference in DNA among individuals
Epigenetics
Heritable changes in gene expression
phenotype not genotype
factors affecting transcription
Transcriptomics
mRNA level
expression level genes
microarray: complementary RNA binding to short sequence. Measuring gene expression level
Proteomics
study of proteins
post translational modifications, shapes and folding of proteins
Metabolomics
study of metabolites
ATP, amino acids: impact