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Why Biological Systems Suddenly Change State: An Intuitive Guide to Freidlin–Wentzell Theory

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  Stochasticity is ubiquitous in biology and neuroscience, manifesting in various forms, including ion channel noise, synaptic variability, gene regulatory fluctuations, noisy population dynamics, and more. Many biological systems spend long periods in a stable “state” and only rarely transition to another state due to noise. For instance, a neuron typically remains inactive but may occasionally trigger a spontaneous spike. Similarly, a gene can switch from the OFF state to the ON state due to rare bursts of transcription factors. Cells can also transition out of metabolic or epigenetic states, populations might shift between different ecological equilibria, and a viral infection can fluctuate between phases of control and uncontrollability. Freidlin–Wentzell theory provides a mathematically rigorous framework to study these phenomena when noise is small but nonzero . It tells you, firstly, h ow likely rare transitions are,    secondly,   h ow fast they occ...

R function conf_int_Accuracy

  R function conf_int_Accuracy <- function(GMTobs, s, nDays = 2, nAnalysts = 2, nPlates = 2, nReplicates = 3, FoldDilution = 2, Threshold = 1, alpha = 0.05) {   # INPUT:   # GMTobs: vector of observed geometric means at each fold dilution   # s: vector of the standard deviations of the log-transformed replicates   # nDays: number of experimental days (default = 2)   # nAnalysts: number of analysts performing the tests in validation (default = 2)   # nPlates: number of plates used per analyst per day (default = 2)   # nReplicates: number of measurements that each analyst performs per plate per day   # FoldDilution: step of the serial dilution (default = 2)   # Threshold: critical threshold of the log-difference between the observed and the true mean (default=1)   # alpha: significance level (default=0.05)   #   # OUTPUT:   # vector of Relative Accuracy calculated at each fold dilution and its confidence interval. In...

Quantifying a biossay: confidence interval of the accuracy

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A bioassay validation is a set of procedures that ensure the precision and accuracy of the test results. Precision refers to the proximity of results to each other, and accuracy is the proximity of measurements results to the true value. Here we want to focus on the accuracy and the building of a confidence interval around it.   Let's design the validation experiments with three possible sources of variability, day, analyst, and plate having nd levels, na levels, and np levels, respectively. Each analyst performs nm measurements per plate per day on each sample. The samples will be serially diluted by a factor of two, resulting in dl dilution levels from 1/1 to 1/(2^(dl-1)). So, the total number of measurements, N, for each dilution level will N=nd*na*np*nm.   To calculate the accuracy , A, we can follow the FDA recommendation [1] of comparing the mean of the measured values with the "true" value, and define accuracy as that is the ratio between the observed geometric m...

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