N-803_SIV_Model

Jonathan W. Cody

This repository contains all the code needed to replicate the following article. MATLAB R2018b or later is required.

Cody JW, Ellis-Connell AL, O’Connor SL, Pienaar E. "Mathematical modeling indicates that regulatory inhibition of CD8+ T cell cytotoxicity can limit efficacy of IL-15 immunotherapy in cases of high pre-treatment SIV viral load."

=========================

To replicate the article, unzip the entire repository into a folder and run the code in the following order below. Results of step #3 are included in the repository in the file 'N803_ForPlots.mat', which allows you to skip to plotting (steps #4,5). To replicate only the MAIN TEXT results, perform steps #1,3,4, but first edit 'N803_collector_2.m' and 'N803_plotter_2.m' (see those scripts for instructions).

'main_shared_2_calibration.m' (runs MSLS and MCMC for both cohorts with shared constants)
supplemental calibrations: -> 'main_shared_2A_calibration.m' -> 'main_shared_2B_calibration.m' -> 'main_shared_2C_calibration.m' -> 'main_shared_2D_calibration.m' -> 'main_single_2_calibration.m'
'N803_collector_2.m' (stores model outputs, parameters, and initial conditions from thinned MCMC sample)
'N803_plotter_2.m' (creates all time-course plots)
'N803_plotter_2_violin.m' (creates violin plots)

=========================

The repository containts the following data (MATLAB .mat files):

'N803_DataSet_1.mat' (Cohort 1 calibration data) Source: Ellis-Connell AL, Balgeman AJ, Zarbock KR, Barry G, Weiler A, Egan JO, et al. "ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment." Journal of virology. 2018;92(3).

'N803_DataSet_2.mat' (Cohort 2 calibration data, validation data) Source: Ellis-Connell AL, Balgeman AJ, Harwood OE, Moriarty RV, Safrit JT, Weiler AM, et al. "Control of Simian Immunodeficiency Virus Infection in Prophylactically Vaccinated, Antiretroviral Treatment-Naive Macaques Is Required for the Most Efficacious CD8 T Cell Response during Treatment with the Interleukin-15 Superagonist N-803." Journal of virology. 2022;96(20).

'Webb_DataSet.mat' (validation data) Source: Webb GM, Li S, Mwakalundwa G, Folkvord JM, Greene JM, Reed JS, et al. "The human IL-15 superagonist ALT-803 directs SIV-specific CD8(+) T cells into B-cell follicles." Blood advances. 2018;2(2):76-84.

'mean_data' (mean across individuals of Ellis-Connell data at each time point; used in supplemental figure S7)

'N803_ForPlots.mat' (model parameter values, initial conditions, and outputs underlying all article figures)

=========================

In addition to the MATLAB scripts referenced above, this repository contains the following functions:

'N803_model_2.m' (solves ODE model for N-803 treatment of SIV)

'N803_model_2A.m' (solves ODEs for alternative model A)

'N803_model_2B.m' (solves ODEs for alternative model B)

'N803_model_2C.m' (solves ODEs for alternative model C)

'N803_model_2D.m' (solves ODEs for alternative model D)

'N803_model_2_naive.m' (solves ODE model for N-803 given to SIV-naive NHP)

'N803_shared_2.m' (calls 'N803_model_2.m', but first solves for ICs and shared parameters to start from two fixed points)

'N803_shared_2A.m' (calls 'N803_model_2A.m', but first solves for ICs and shared parameters to start from two fixed points)

'N803_shared_2B.m' (calls 'N803_model_2B.m', but first solves for ICs and shared parameters to start from two fixed points)

'N803_shared_2C.m' (calls 'N803_model_2C.m', but first solves for ICs and shared parameters to start from two fixed points)

'N803_shared_2D.m' (calls 'N803_model_2D.m', but first solves for ICs and shared parameters to start from two fixed points)

'N803_single_2.m' (calls 'N803_model_2.m', but first solves for ICs and parameters to start from one fixed point)

In 'Analyzer' folder:

'calibrator.m' (called by 'main.m' scripts; calibrates model parameters via multi-start local-search)

'calibrator_plot.m' (called by 'main.m' scripts; plots results from 'calibrator.m')

'copyfields.m' (called by 'gridplot.m'; copies fields from one scalar structure to another)

'costFun_NLL.m' (called by 'main.m' scripts; model cost calculator (NLL,SSE,MSE w/additional options))

'gridplot.m' (called by 'N803_plotter_2.m'; creates a grid of plots (alternative to MATLAB's 'subplot'))

'linemaker.m' (called by 'gridplot.m'; plots lines to current axis, with a variety of options)

'looper.m' (called by 'calibrator.m'; loops through and operates on a structure array)

'MCMCsampler.m' (called by 'main.m' scripts; performs uncertainty quantification via markov chain monte carlo)

'parplotter.m' (called by 'N803_plotter_2_parameters.m'; plots parameter distributions)

'performPT.m' (called by 'MCMCsampler.m'; parallel tempering MCMC algorithm) Source: https://github.com/ICB-DCM/PESTO/blob/master/private/performPT.m

'prepper.m' (called by 'main.m' scripts; normalizes a data set and provides several useful outputs)

'sampler.m' (called by 'calibrator.m'; samples a parameter space via latin hypercube sampling)

'tickmaker.m' (called by 'N803_plotter_2.m'; creates axis tick labels)

'violin.m' (called by 'parplotter.m'; creates violin plots) Source: https://github.com/bastibe/Violinplot-Matlab/blob/master/Violin.m

ElsjePienaarGroup/N803_SIV_Model

About

Resources

Uh oh!

Stars

Watchers

Forks

Releases 2

Languages