A discussion of tools and resources for mechanistic within-host modeling
Slides: https://www.andreashandel.com/presentations/
5/17/23
Acknowledgements
- Lot’s of people contributed. See the websites for each tool/resource.
- NIH funding.
Format for this presentation
- I’ll start with a very short introduction to the topic.
- The bulk will be show & tell demonstrations.
- I’ll focus on tools/resources from our group.
- There should be lots of time for questions and discussion.
Phenomenological/non-mechanistic/(statistical) models
- Most widely used types of models, useful (almost) everywhere one has data
- Look for patterns in data
- Do not describe mechanisms leading to the observed outcomes (data)
y=b0+b1x1+b2x2+...
Mechanistic/process/simulation models
- Are widely used in all areas of science.
- Are simplified representations of specific processes/mechanisms.
- Can be implemented as various different types of mathematical/computer models.
- Can be used without and with data (and then also become statistical)
Bacteria˙B=gB(1−BBmax)−dBB−kBIImmune Response˙I=rBI−dII
Simulation model uses
- Explore the behavior of a system.
- Make predictions about the behavior of a system.
- With data: Perform inference, test hypotheses (doing stats).
Simulation model types
- Compartmental models are the simplest and most widely used.
- Most commonly implemented as ordinary differential equations (ODEs).
˙B=gB(1−BBmax)−dBB−kBI˙I=rBI−dII
Simulation model types
- Agent-based or network models are more detailed/complex.
- Can be more realistic, but are more data-hungry and computationally demanding.
Questions/Discussion
- This was a minimal background section to set the stage.
- See Handel et al 2020 Nat Rev Imm for some more in-depth introduction.
- I plan to now show various resources/tools for mechanistic/simulation modeling.
- Any questions/feedback/comments before we move on?
Simulation Modeling in Immunology (SMI)
- Free online website hosts videos, slides, readings: https://andreashandel.github.io/SMIcourse/
- Materials created as “by-product” of 15y of teaching an immunology and within-host modeling course with Paul Thomas at SISMID.
SMI Strengths/Weaknesses
- The good
- Decent amount of introductory material (videos, slides, readings)
- Immunology and modeling
- All free
- The bad
- No guided/curated experience
- Coverage of topics is uneven/idiosyncratic
- Not fully polished
SMI Questions/Discussion
DSAIRM R package
- R package to learn/explore mechanistic simulation models: https://ahgroup.github.io/DSAIRM/
- Modular design, starts with no-code approach, allows advancement to coding.
- Each simulation app comes with model description and a set of suggested tasks that teach a specific modeling concept.
- Full solutions to all tasks are available (on request).
Learning DSAIRM
- The goal is to have a very low barrier to use. If you can use Excel/Prism, you can use this 😁.
- Main resource is package website: https://ahgroup.github.io/DSAIRM/
- See some materials on the SMI site.
- Also this paper in BMC Immunology.
DSAIRM Strengths/Weaknesses
- The good
- Starts out completely code-free.
- Good number of within-host modeling topics are covered.
- Set of guided exercises/tasks to help learn the material.
- Full access to underlying model code.
- The bad
- Only the models I wrote are available.
- Custom models (e.g., for research) will require adapting one of the existing models, which means having to write code.
- Package name is maybe awkward (taking suggestions for better naming).
DSAIRM Questions/Discussion
modelbuilder R package
- Graphical/non-coding approach to building custom models.
- Usable (I think) but still in progress.
- Main resource is package website: https://ahgroup.github.io/modelbuilder/
modelbuilder Strengths/Weaknesses
- The good
- You can build your own models (or adapt existing ones).
- You can explore your models through the graphical interface.
- You can get different versions of the model code for further use.
- Has lots of overall potential 😄.
- The bad
- User interface not fully polished and robust.
- No option to load and fit data (do stats).
- Not suitable for big models.
- Potential only partially realized 😄.
modelbuilder Questions/Discussion
flowdiagramr R package
- Side project: automated way to make model diagrams.
- Can produce nice diagrams of not-too-complex models.
- Main resource is package website: https://andreashandel.github.io/flowdiagramr/
flowdiagramr Strengths/Weaknesses
- The good
- Helps with potentially annoying model drawing task.
- Is highly configurable and easy to use.
- The bad
- Currently can’t handle more complex models (e.g. 3-way interaction).
- Still not fully tested, might still contain a good bit of bugs.
flowdiagramr Questions/Discussion
Summary and more discussion
- I described a few tools/resources that might be useful for individuals who want to learn about or start using mechanistic/simulation models.
- I very much appreciate feedback - both now and at any future time.
- Contributions to any of these tools/packages are always very welcome!
- Slides: https://www.andreashandel.com/presentations.html
- Tools: https://www.andreashandel.com/projects.html
A discussion of tools and resources for mechanistic within-host modeling Slides: https://www.andreashandel.com/presentations/ Andreas Handel 5/17/23