Readme for the repository

This is a repository for the corresponding paper "Pseudo-time trajectory of single cell lipidomics".

To reproduce the workflows and figures of the paper, please follow the instructions below.

Requirements

The code provided here was originally run with python 3.11.1, though -- just as for the software packages -- we estimate that newer version should also work. The code should be compatible with Windows, MacOS and Linux. They Key software packages used are: * pyPESTO v0.3.1 (pip installable) * AMICI v0.18.0 (pip installable, but requires a C++ compiler, see installations instructions) * Fides v0.7.8 (pip installable) * simplesbml v2.3.0 (pip installable)

All other packages should be automatically installed with the above packages.

Repository structure

The repository contains the following structure:

• Code3labels: Code for the analysis of the 3 labels dataset
• Code_multilabels: Code for the analysis of the multilabels dataset
• Results_h5: Results of the optimization, which can be used to create the figures without running the optimization again. The structure of a single .hdf5 File can be found here.

We also provide the base model (See Figure 2A) and an example model with 3 labels as SBML files.

Running Code

We split the Code into two workflows: 1. 3 Label Study Workflow: This workflow creates the models and data and runs the optimization of the main dataset of the paper. Visualizations that recreate parts of the figures are included in a separate Jupyter notebook. 2. Multilabel Study Workflow: This workflow creates the models and data and runs the optimization of the multilabels dataset. Visualizations that recreate parts of the figures are included in a separate Jupyter notebook.

Each workflow can be run independently and the folders are set up such that only that specific folder is needed to run the code (even though this creates some redundancy). Additionally, as the optimization takes a substantial amount of time, the creation of data, models and optimization can be skipped. The original results of the optimization are provided in the Results_h5 folder, which can be used to create the figures without running the optimization again. A separate folder "Figure_1" contains a very small model, that has been used to create Figure 1 of the paper.

3 Label Study Workflow

1. Run create_parameters.py to create the parameter sets. You can skip this step if you want to use the precomputed parameter sets in the Code_3_labels folder. shell python create_parameters.py
2. Run sbml_model_create.py to create the sbml and petab models. They will be saved the folder Petab_models_230829/3_labels. shell python sbml_model_create.py
3. Run optimization_model.py to run the optimization for the models. The results will be saved in the folder Results_h5. You either specifiy an index of the model to run (counting from zero, corresponding to the parameter set) in the command line, or run the command with "ALL" instead to run all models. This will be computationally intensive!! shell python optimization_model.py $INDEX or shell python optimization_model.py ALL
4. Visualizations The notebooks are set up to use the results from the Results_h5 folder, so you don't need to run the optimization again. Though the sbml_model_create.py should be run beforehand. Specifically, the visualizations are:
5. Visualizations_3_labels.ipynb: Creates Figure 4B, Figure 5B,C of the paper. This visualization uses the results from the Results_h5 folder.
6. visualizations.py: Creates the basis for Figure 2A. Also uses the results from the Results_h5 folder.

For a more detailed description of what each files does see Code description.

Multilabel Study Workflow

1. Run create_parameters.py to create the parameter sets. You can skip this step if you want to use the precomputed parameter sets in the Code_multilabels folder. shell python create_parameters.py
2. Run sbml_model_create.py to create the sbml and petab models. They will be saved the folder Petab_models_230829/multilabels. shell python sbml_model_create.py
3. Run optimization_model.py to run the optimization for the models. The results will be saved in the folder Results_h5. While you can specify the index of the model, the index gets converted to the corresponding parameter set and label. In practice this means that supplying an index $ind$, we get the parameter index $i{param} = ind \mod 200$ and the number of labels $n{labels} = ind // 200$. It might be preferred to run the command with "ALL" instead to run all models. This will be computationally intensive!! shell python optimization_model.py $INDEX or shell python optimization_model.py ALL
4. Visualizations The notebooks are set up to use the results from the Results_h5 folder, so you don't need to run the optimization again. Though the sbml_model_create.py should be run beforehand. Specifically, the visualizations are:
5. Visualizations_multilabels.ipynb: Creates Figure 6 of the paper. This visualization uses the results from the Results_h5 folder.

Visualization of Figure 1

The folder Folder1_creation serves to create Figure 1B. The notebook Figure1. ipynb can be run without any dependencies on other folders. This visualization does not use any model or result from before, but rather a Toy Model.

Code description

Here is a short description of the essential code in the repository:

• Code3labels and Code_multilabels:
  • create_parameters.py: Function to create the parameter sets.
  • sbml_model.py: Variables such as Parameter Values and Reactions for the base model.
  • sbmlmodelutils.py: Helper functions and rules to create labeled models.
  • sbmlmodelcreate.py: Running this file creates the models.
  • parameter_set.csv: Parameter sets for the models.
  • reaction_table.tsv: Reactions of the models.
  • optimization_model.py: Run the optimization for the models.
• Visualizations:
  • analyze_results.py: Defines the CumulativeResult class used in the visualizations.
  • visualizations.py: Creates the basis for Figure 2A.
  • Visualizations3labels.ipynb: Creates Figure 4B, Figure 5B,C of the paper.
  • Visualizations_multilabels.ipynb: Creates Figure 6 of the paper.
  • Figure1creation:
    • Figure1.ipynb: Creates Figure 1B.
• Results_h5:
  • Results of the optimization, which can be used to create the figures without running the optimization again. For an overview of the structure of each .hdf5 file, we refer to the pyPESTO documentation.