Uncovering the dynamic effects of DEX treatment on lung cancer by integrating bioinformatic inference and multiscale modeling of scRNA-seq and proteomics data

Dexamethasone (DEX) has shown anti-cancer efficacy and anti-estrogenic activity in human non-small cell lung cancer (NSCLC)； hence, understanding the underlying mechanisms that affect the implementation and effectiveness of lung cancer therapeutics is vital. In this study, we combine the power of Bioinformatics and Systems Biology to uncover functional and signaling pathways of drug treatment using bioinformatics inference and multiscale modeling of both scRNA-seq data and proteomics data. Here, we propose a comprehensive multiscale model of tumor regulation centered on both TGF-β-induced and ERBB-amplified signaling pathways to characterize the dynamics effects of DEX therapy on lung cancer cells. We also provided predictions of different doses to illustrate the trend and therapeutic potential of DEX treatment, and therefore can be further applied to other computational studies in tumorigenesis and oncotherapy.

Structure of the repository

DEX model

For Windows users: matlab -nodisplay -nosplash -nodesktop -r “run_model ; exit”
For Mac users: /Applications/MATLAB_R2022a.app/bin/matlab -nodisplay -nosplash -nodesktop -r “run_model ; exit”
Lines above run the model and plot the graphs with the parameter values loaded. Notice the MATLAB version should be modified to the version you have. Please make sure MATLAB R2017a or any later version is downloaded.

┌──ga_cancer.m
├──direct.m
├──model.m
├──fitness.m
├──run_model.m
└──level_doses.m

• ga_cancer.m: contains the script for running Genetic Algorithm for optimizing parameters.
• direct.m: contains the script for running Direct Optimization Algorithm for optimizing parameters.
• model.m: contains the script for ordinary differential equations of tumorigenesis regulatory network model
• fitness.m: contains the script for objective functions of parameter optimizations intumorigenesis regulatory network model
• run_model.m: contains the script for running model with parameters loaded and plotting simulated protein profiles and expression level of signature genes
• level_doses.m: contains the script for plotting simulated levels of signature genes under one, two, and three doses of DEX treatment respectively

Bioinformatics_anlaysis

┌──main.R
├──TF_analysis.R
├──enrich_analysis.R
└──clinical_analysis.R

• main.R: contains the script for main bioinformatics analysis with optional choice of downstream alaysis.
• TF_analysis.R: contains the script for identifying the upstream transcriptional factors of DEG list.
• enrich_analysis.R: contains the script for functional enrichment analysis
• clinical_analysis.R: contains the script for analyzing the clinical significance

Command line instructions

Rscript main.R

Software Requirement

MATLAB; R

Contact

If you have any further questions or suggestions, please contact chenm@wfu.edu or qsong@wakehealth.edu