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RestoreNet (version 1.0.1)

Random-Effects Stochastic Reaction Networks

Description

A random-effects stochastic model that allows quick detection of clonal dominance events from clonal tracking data collected in gene therapy studies. Starting from the Ito-type equation describing the dynamics of cells duplication, death and differentiation at clonal level, we first considered its local linear approximation as the base model. The parameters of the base model, which are inferred using a maximum likelihood approach, are assumed to be shared across the clones. Although this assumption makes inference easier, in some cases it can be too restrictive and does not take into account possible scenarios of clonal dominance. Therefore we extended the base model by introducing random effects for the clones. In this extended formulation the dynamic parameters are estimated using a tailor-made expectation maximization algorithm. Further details on the methods can be found in L. Del Core et al., (2022) .

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Version

Install

install.packages('RestoreNet')

Monthly Downloads

180

Version

1.0.1

License

GPL-3

Maintainer

Luca Del Core

Last Published

February 15th, 2024

Functions in RestoreNet (1.0.1)

get.dx

Time-adjacent increments of the cell counts
nQ

E-step function Q
rmvNorm

Random generator from a Multivariate Normal distribution
rndEffModelFitting

Fit random-effects model
get.M

Design matrix M
nullModelFitting

Fit base model
norm2

Euclidean 2-norm
tr

Matrix trace
rndEffModelStats

Base and random-effects model statistics
ngQ

Gradient of the E-step function Q
get.sim.tl

\(\tau\)-leaping simulation algorithm
ldet

Matrix determinant
relErr

Multivariate relative error
ny_u

Conditional negative log-likelihood
VEuy

\(E[u \vert y]\) and \(V[u \vert y]\)
fit.null

Fit the base (null) model
get.rescaled

Rescaling a clonal tracking dataset
fit.re

Fit the random-effects model
get.scatterpie

Clonal pie-chart
get.boxplots

Clonal boxplots
dD2

Gradient of \(V[u \vert \theta]\)
dmvNorm

Multivariate Normal density function
BhattDist

Bhattacharyya distance
dBu

Gradient of \(E[u \vert \theta]\)
get.nl

Negative log-likelihood of the base (null) model
get.gnl

Gradient of the negative log-likelihood of the base (null) model
get.V

Net-effect matrix
Y_RM

Rhesus Macaque clonal tracking dataset
KLDiv

Kullback-Leibler divergence
condAIC

Conditional AIC (cAIC)
compile.h

Generate hazard function
get.W

Stochastic covariance matrix W