DOI: 10.5061/dryad.dz08kps5v
title: 'CellTrajectory' for cellular automata modelling of leukaemic stem cell dynamics in acute myeloid leukaemia: insights into predictive outcomes and targeted therapies

description: Acute myeloid leukaemia (AML) is a haematologic malignancy with high
 relapse rates in both adults and children. Leukaemic stem cells (LSCs) are
 central to leukaemopoiesis, treatment response, and relapse and frequently
 associated with measurable residual disease (MRD). However, the dynamics
 of LSCs within the AML microenvironment are not fully understood. This
 study utilized three-dimensional cellular automata (CA) modelling to
 simulate LSC behaviour and treatment response under induction
 chemotherapy. Our study revealed: (1) a correlation between LSC
 persistence post-induction chemotherapy and risk of AML relapse; (2) MRD
 negativity based on LSC count may not reliably predict outcomes,
 supporting clinical evidence that patients with MRD-negative status can
 still be at risk of relapse; (3) prolonged persistence of LSCs
 post-chemotherapy without disruption of normal haematopoiesis, aligning
 with clinical observations of dormant AML clones; (4) early LSC dynamics
 post-induction chemotherapy, characterized by stochastic behaviours and
 movement velocities, are insufficient predictors of long-term prognosis;
 and (5) a distinct spatiotemporal organization of LSCs in later phases
 post-induction chemotherapy is correlated with long-term outcomes. Our
 modelling results provide a theoretical and clinical framework for AML
 research, and future clinical data validation could refine the utility of
 CA modelling for oncological studies.
description: The collection of data was processed using our custom computer
 programs.
description: # 'CellTrajectory' for cellular automata modelling of leukaemic
 stem cell dynamics in acute myeloid leukaemia: insights into predictive
 outcomes and targeted therapies
 [https://doi.org/10.5061/dryad.dz08kps5v](https://doi.org/10.5061/dryad.dz08kps5v) 'CellTrajectoryVer2': This research focuses on computer simulations of cell dynamics, including cell division, differentiation, apoptosis, and movement in three-dimensional (3D) space, using the 'Biosim' code. The output file "mark.dat" from 'Biosim' contains cell coordinates in 3D space, cell lineage denoted as MK.ID, and cell positions (PREPOS) at time t-1, a one-time step before, for all cells at each time point t during the simulation. This output file was used as input for our custom software 'CellTrajectoryVer2' to reconstruct cell trajectories. ## Description of the data and file structure Installation and Setup: 1. Installation: * Double-click the 'CellTrajectoryVer2.exe' repository to install the necessary files, including 'CellTrajectory.exe.' * The necessary files are installed in the folder `C:\Cell`. 1. Running 'CellTrajectory': * Double-click 'CellTrajectory.exe' in the folder `C:\Cell` to open the software. * The software comprises two sequential processes for assigning input information:　‘Prepare in advance’ and ‘Creation of cell trajectory data’. Process Steps: 1. Prepare in Advance (Figure 1, left): * Pre-process 'mark.dat' to classify data by MK.ID for cell lineage. * Enter the path to 'mark.dat' and specify the folder for the output files. * Output files ‘mark*.dat’ are generated, named mark1.dat, mark2.dat, etc., for normal cell lineage, and mark20001.dat, mark20002.dat, etc., for leukemic cell lineage. * Press the ‘execute’ button. 1. Creation of Cell Trajectory Data (Figure 1, right): * Reconstruct all cell trajectories during the simulation based on PREPOS. * Select a target cell from all cells existing at an arbitrary ending time point (t_end) and assign the coordinates (x, y, z) of the target cell, the focused MK.ID, t_end, and the starting time point (t_start). * Specify the corresponding mark*.dat file and the name of an output file. * Press the 'extract the target data' button. * Press the 'create the trajectory data' button and assign the name of the final output file, which will include data for all cell trajectories. Source Codes: * The source codes for cell trajectory reconstruction in ‘CellTrajectory.exe’ are ‘MainForm.cs’ and ‘PointXYZ.cs.’ Visualization: * Cell trajectories in 3D space were visualized using Origin 2022 (OriginLab). * An interface, 'cellgraph_v5_2021b.opx,' was developed to facilitate the transfer of trajectory data from the final output file of 'CellTrajectoryVer2' to Origin 2022. * To use this interface, import 'cellgraph_v5_2021b.opx' into the opened Origin window by dragging and dropping it. Once imported, the final output file can be imported into Origin, allowing for the representation of cell trajectories in 3D space. ## Sharing/Access information NA