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Studies

Computational studies and literature-validated simulation experiments.

Running studies

Each study lives in its own subdirectory with a preset.toml, scripts, scenarios, and results.

source ~/biodynamo/build/bin/thisbdm.sh

# Diabetic treatment comparison (baseline + 8 treatments, ~3-4h)
./studies/diabetic-wound/treatment.sh

# Adaptive combo search (surrogate-guided, ~30-45min)
./studies/diabetic-wound/adaptive.sh

# Skin type comparison (normal vs aged vs diabetic)
./studies/wound/skin-comparison.sh

# Tumor growth kinetics
./studies/tumor/study.sh

# Experiment scenarios (7 experiments)
./studies/run-scenarios.sh

Study scripts

Script Python backend Description
diabetic/treatment.sh treatment_study.py Baseline + 8 treatments, Excel workbook
diabetic/adaptive.sh adaptive_study.py Surrogate-guided combo search with synergy detection
wound/skin-comparison.sh batch/batch.py Normal / aged / diabetic skin profiles
tumor/study.sh batch/batch.py BCC/SCC growth rate validation
run-scenarios.sh scenario_runner.py Experiment scenarios across all studies

Experiment scenarios

TOML-defined experiments in studies/diabetic-wound/scenarios/, each exploring a different axis of diabetic wound healing:

Scenario File Configs Runs
Severity spectrum severity_spectrum.toml 5 levels (0.5x to 1.5x) 5/config
Biofilm infection biofilm_infection.toml 4 (control, early/late, +doxy) 5/config
Treatment timing treatment_timing.toml 12 (3 treatments x 4 windows) 5/config
Wound size wound_size.toml 4 (1.5mm to 8mm) 5/config
Aged + diabetic aged_diabetic.toml 4 phenotypes 5/config
Chronic wound (90d) chronic_wound.toml 4 (severe + biofilm + rescue) 3/config
Immune tuning immune_tuning.toml 4 (restore one axis) 5/config
bash studies/run-scenarios.sh                                               # all scenarios
bash studies/run-scenarios.sh studies/diabetic-wound/scenarios/wound_size.toml   # single scenario
bash studies/run-scenarios.sh --quick                                       # all with 2 runs

Literature-validated observables

Timeseries validated against published consensus curves (RMSE < 15%).

Observable Consensus CSV Key sources Condition
Wound closure closure_kinetics_punch_biopsy.csv Cukjati 2001, Gonzalez 2016 Normal
Inflammation inflammation_timecourse.csv Eming 2007, Koh 2011 Normal
Immune cells immune_cell_kinetics.csv Kim 2008, Rodero 2010 Normal
Myofibroblasts myofibroblast_kinetics.csv Darby 2014, Desmouliere 1995 Normal
Collagen collagen_deposition.csv Zhou 2013, Murphy 2012 Normal
Diabetic closure diabetic_closure_kinetics.csv Mirza 2011, Louiselle 2021 Diabetic
Diabetic inflammation diabetic_inflammation_timecourse.csv Wetzler 2000, Mirza 2011 Diabetic
Diabetic immune cells diabetic_immune_cell_kinetics.csv Khanna 2010, Wang 2020 Diabetic
Tumor growth tumor_growth_rate.csv Kricker 2014, Fijalkowska 2023, Sykes 2020 Tumor

Parameter-validated modules

Modules with parameter values sourced from literature (not timeseries-validated).

Module Status Parameters Key sources
Angiogenesis Enabled VEGF diffusion, sprout rate, capillary density Schugart 2008 (10.1016/j.jtbi.2008.06.042), Flegg 2012
MMP Enabled Decay, production rates, TIMP interaction Nagase 1999, Ladwig 2002 (10.1067/mjd.2002.124601)
Fibronectin Enabled Deposition rate, degradation Clark 1990, Grinnell 1984
Scar Enabled Collagen-based scar scoring, remodeling Ogawa 2017 (10.3390/ijms18030606), Gauglitz 2011
Hemostasis Disabled Platelet plug, fibrin mesh, clotting cascade Brass 2010, Reininger 2006
Perfusion Enabled O2 transport, vascular delivery Johnson 1971, Stucker 2002
Dermis Enabled Dermal ECM, thickness, hydration Braverman 2000, Singer 1999

Treatments

Treatment Mechanism Key sources Parameters modified
Anti-inflammatory Anti-TNF-alpha, accelerates M1-to-M2 Goren 2007 M1 decay, M2 transition
Combination Multi-modal (anti-infl + HBO + doxy + moisture) Composite Multiple
Doxycycline Sub-antimicrobial MMP inhibitor Siqueira 2010, Smith 1999 MMP production, collagen decay
Growth factor Becaplermin (PDGF-BB) Steed 2006, Smiell 1998 KGF rate, chemotaxis
HBO Hyperbaric oxygen therapy Londahl 2010, Fedorko 2016 O2 delivery, VEGF
Moisture Advanced dressings (hydrogel/foam) Junker 2013, Kannon 1995 Water recovery, evaporation
MSC Mesenchymal stem cell therapy Cao 2017 Immune modulation, growth factors
NPWT Negative pressure wound therapy Morykwas 1997, Armstrong 2005 Perfusion, granulation

Coded but disabled

Modules with implementation complete but disabled by default (awaiting calibration or validation data).

Module Config key Sources Notes
Biofilm skin.biofilm.enabled James 2008, Bjarnsholt 2008, Davis 2008 Bacterial colonization, immune evasion
pH skin.ph.enabled Schneider 2007, Gethin 2007 Wound bed pH gradient, enzyme activity
Hyaluronan skin.hyaluronan.enabled Toole 2004, Stern 2006 HAS2-driven HA synthesis, hydration
Elastin skin.elastin.enabled Kielty 2002, Almine 2012 Tropoelastin deposition, cross-linking
Hemostasis skin.hemostasis.enabled Brass 2010, Reininger 2006 Platelet activation, fibrin scaffold

Potential expansions

Areas with published mechanistic data that could extend the model.

Feature Biological basis Candidate sources Complexity
Temperature therapy Accelerated enzymatic rates, vasodilation Ikeda 2005, Kloth 2002 Low
Oxygen therapy (topical) Direct O2 application vs HBO Gordillo 2007 Low
pH treatment Acidic dressings shift enzyme optimum Schneider 2007 Medium
HA treatment Exogenous hyaluronan scaffolds Tolg 2014, Voigt 2012 Medium
Cellular senescence SASP-driven chronic inflammation Demaria 2014, Wilkinson 2019 High
Oxidative stress ROS-mediated tissue damage Schafer 2008, Sen 2009 High
Basement membrane Laminin/collagen IV reassembly Rousselle 2019 High

Validation pipeline

# Run literature validation on any metrics CSV
python3 literature/validate_all.py output/skibidy/metrics.csv

# Check source integrity (DOIs referenced in configs vs SOURCES.yaml)
python3 literature/check_sources.py

# 10-run batch consensus with validation
python3 batch/batch.py -n 10 --skin normal --study wound --validate
python3 batch/batch.py -n 10 --skin diabetic --study diabetic-wound --validate

Example outputs

Pre-generated results are included so you can inspect output without running simulations.

Study Example file Description
Diabetic treatments diabetic/example/ 8-treatment comparison Excel workbook
Adaptive combos diabetic/adaptive-example/ Surrogate predictions + synergy analysis