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# N-803_SIV_Model
Jonathan W. Cody

This repository contains all the code needed to replicate the following journal article, soon to be submitted to PLoS Computational Biology. MATLAB R2018b or later is required.
This repository contains all the code needed to replicate the following journal article, submitted to PLoS Computational Biology. 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."

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To replicate the article, unzip the entire repository into a folder and run the code in the following order below. Steps #1,2 are lengthy (~1 week each). Results of step #3 are included in the repository in the file 'N803_MCMC.mat', which allows you to skip to plotting (steps #4,5).
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).

1. "main_shared_calibration_2022_08_18.m" (runs MSLS and MCMC for both cohorts with parameters shared)
1. "main_shared_2_calibration" (runs MSLS and MCMC for both cohorts with shared constants)
2. "main_singles_calibration_2022_09_25.m" (repeat with parameters not shared)
3. "N803_collector_2.m" (stores model outputs, parameters, and initial conditions from thinned MCMC sample)
4. "N803_plotter_2.m" (creates all time-course plots)
5. "N803_plotter_2_parameters.m" (creates parameter violin plots)
5. "N803_plotter_2_violin.m" (creates violin plots)

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

"N803_DataSet_1.mat" (Cohort 1 calibration data)
'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)
'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)
'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.

'N803_MCMC.mat' (model parameter values, initial conditions, and outputs underlying all article figures)
'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)

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