HTLV-1 Hybrid Model

This repository contains the code for a model of within-host Human T-Lymphotropic Virus Type-1 (HTLV-1) persistence, developed by Daniel J. Laydon, Vikram Sunkara, Lies Boelen, Charles R.M. Bangham and Becca Asquith. Details available at https://doi.org/10.1371/journal.pcbi.1007470

Scripts contains functions for a hybrid model of chronic HTLV-1 infection and within-host persistence. The model divides HTLV-1 proviral load (i.e. the number of infected cells) into clones, where clones are defined as populations of indentically infected cells with a common site of proviral integration. Clones proliferate via mitotic spread. Clones are created by infectious spread.

The hybrid model is comprised of two systems; i) deterministic system modelled by series of ODEs (for large clones); ii) stochastic system modelled by multiple birth-death processes (for smaller clones).

The model is written in R.

Scripts

• CloneBirthDeath.R contains functions for birth-death processes and the change in clone frequency probabilities over time.
• CloneTrajectories.R calls functcions from CloneBirthDeath.R to store look-up tables for the summary statistics of clone frequency probability distributions for each clone at each age or time. These tables are used when running the model.
• HybridFunctions.R contains functions for running the hybrid model.
• QuickGridSearch.R runs the hybrid model for a grid of values of the rate of infectious spread, given a fixed rate of mitotic spread.
• OptimizeFit.R fits the hybrid model via one-dimensional optimization, using values returned from QuickGridSearch.R to narrow the search space.
• FitHybrid.R calls i) CloneTrajectories.R, ii) QuickGridSearch.R and iii) OptimizeFit.R to fit the rate of infectious spread for a single patient data set.

Inputs

The estimated clone frequency distributions for each patient blood sample are given in directory EstDists.

Description

Patient blood sample characteristics are given in PatientSampleInfo.txt.