'Biosim' for cellular automata modelling of leukaemic stem cell dynamics in acute myeloid leukaemia: insights into predictive outcomes and targeted therapies
Data files
Jan 17, 2025 version files 43.05 MB
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apopDialog.cpp
3.78 KB
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apopDialog.h
1.38 KB
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biosim.aps
79.53 KB
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biosim.clw
18.68 KB
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biosim.cpp
2.26 KB
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biosim.dsp
5.50 KB
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biosim.dsw
543 B
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biosim.h
855 B
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biosim.ncb
17.92 MB
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biosim.opt
48.64 KB
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biosim.plg
3.61 KB
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biosim.rc
36.89 KB
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biosim.sln
1.10 KB
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biosim.suo
32.77 KB
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biosim.vcproj
12.02 KB
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biosim.vcxproj
8.99 KB
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biosim.vcxproj.filters
3.95 KB
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biosim.vcxproj.user
168 B
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biosimDoc.cpp
1.26 KB
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biosimDoc.h
1.01 KB
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biosimView.cpp
72.71 KB
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biosimView.h
2.38 KB
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bone.dat
10.70 MB
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cell.cpp
41.18 KB
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cell.h
628 B
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confDialog.cpp
4.23 KB
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confDialog.h
1.36 KB
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data.dat
2.80 KB
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evilDialog.cpp
1.94 KB
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evilDialog.h
910 B
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initcellDialog.cpp
5.39 KB
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initcellDialog.h
1.33 KB
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MainFrm.cpp
1.84 KB
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MainFrm.h
1.43 KB
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markDialog.cpp
1.11 KB
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markDialog.h
735 B
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markDialog1.cpp
2.68 KB
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markDialog1.h
1.32 KB
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README.md
2.94 KB
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removaldialog.cpp
5.74 KB
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removaldialog.h
1.25 KB
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res_out.dat
0 B
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res_out.sim
3.46 KB
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res_out.ste
14 MB
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resource.h
10.99 KB
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scaleDialog.cpp
1.55 KB
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scaleDialog.h
953 B
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StdAfx.cpp
235 B
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StdAfx.h
646 B
Abstract
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.
README: 'Biosim' 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.qbzkh18s4
Biosim: A Three-Dimensional (3D) Cellular Automaton (CA) Model for LSC-driven Acute Myeloid Leukemia (AML) with Chemotherapy
Biosim is a 3D CA-based AML model developed as a C++ project in Microsoft Visual Studio. It is designed to visualize and analyse leukemic stem cell (LSC) dynamics, thereby enhancing our understanding of treatment responses and clinical outcomes.
Description of the data and file structure
Components:
The Visual Studio Solution comprises Header Files (.h), C++ Source Files (.cpp), and Resource Files, primarily generated using the Microsoft Foundation Class (MFC) Library.
Primary C++ Source Files and Their Functions:
- cell.cpp: Implements the 3D CA-based AML model for spatiotemporal simulations.
- biosim.cpp: Central to the Biosim application, defining the CBiosimApp application class.
- MainFrm.cpp: Defines the CMainFrame class, controlling SDI frames.
- biosimDoc.cpp: Defines the CBiosimDoc class, providing specialized document data.
- biosimView.cpp: Defines the CBiosimView class, used to view CBiosimDoc objects.
- StdAfx.cpp: Builds a pre-compiled header (PCH) file (biosim.pch) and a pre-compiled object file (StdAfx.obj).
Dialog Implementation Files:
- apopDialog.cpp: Dialog for changing apoptosis settings.
- confDialog.cpp: Dialog for changing transit time settings.
- evilDialog.cpp: Dialog for setting leukemic stem cell generation in space.
- initcellDialog.cpp: Dialog for setting initial numbers of cells at respective stages.
- markDialog1.cpp: Dialog for activating and setting values for the marking function.
- removalDialog.cpp: Dialog for activating and setting values for forced removal.
- scaleDialog.cpp: Dialog for setting scale ranges for graphs.
Input/Output Data Files:
- bone.dat: Initializes the distribution of objects in 3D cellular space, assigning state numbers representing bone, vessel, biological cell, or vacant unit to each XYZ coordinate.
- data.dat: Initializes parameters for the initial number of cells at respective stages, transit times, and parameters for the forced removal and marking function.
- res_out.dat: Outputs the time history of cell populations in 3D space.
- res_out.sim: Automatically saves parameter settings from the last run.
- res_out.ste: Automatically saves spatial states with 3D coordinates from the last run.
- mark*.dat: Outputs status information of the marked cells, with * denoting the automatically incremented output interval number.
Running the Project:
- Start Microsoft Visual Studio and open the solution file
biosim.sln
. - Build the project.
- Run the code by selecting either 'Start Debugging' or 'Start Without Debugging'.
Sharing/Access information
NA
Methods
The collection of data is processed using our custom computer programs.