Integrating large- to high-dimension data in mechanistic model: Application to modeling response to vaccination?
Date: Thursday 2nd April 2026
Time: 15:00 - 16:00 (GMT) / 16:00 - 17:00 (CET)
Location: Online via Zoom
Speakers: Melanie Prague (INRIA Bordeaux Sud-Oest Center)
Who is this event intended for?:
Statisticians, Mathematicians, Modelers, working in vaccine development
What is the benefit of attending?:
Be aware of new R packages allowing to integrate high-dimension markers in mechanistic models.
Cost
This webinar is free to both Members of PSI and Non-Members.
Registration
To register for this event, please click here
Overview
Mechanistic models are widely used to describe and explain biological processes over time. However, they typically rely on a limited number of observable compartments and sparse longitudinal data. As a result, these models are often either too simple to capture complex biological phenomena or they face identifiability issues, particularly when considering interindividual variability in the form of nonlinear mixed-effects models based on systems of differential equations. In parallel, with ongoing technological advances, longitudinal high-throughput data (e.g., -omics, including transcriptomics and proteomics data) are increasingly available in various contexts and could bring valuable information into mechanistic models to better capture underlying biological processes. However, integrating such high-dimensional data to inform the dynamics remains a major challenge, both mathematically and for broader interpretation in public health applications.
In this talk, Melanie will present two complementary approaches for integrating large- to high-dimensional biomarkers into mechanistic models. The first approach, called lasso-SAMBA, addresses robust covariate selection in ODE-based non-linear mixed-effect models. It extends the original SAMBA algorithm (which is an iterative model-building algorithm that fastly and sequentially identifies relevant covariates on parameters while estimating model using the SAEM algorithm) by replacing stepwise inclusion with Lasso regression combined with stability selection, ensuring a more reliable identification of relevant covariates while preserving the monotonic decrease of the information criterion. The second approach uses observed -omics data to infer the dynamics of unobserved immune compartments. It relies on an iterative algorithm that alternates between a regularization step, which identifies the most informative biomarkers through penalized likelihood derivatives, and a mechanistic inference step, where population parameters are estimated using the SAEM algorithm in Monolix. This framework enables the selection of biomarkers whose temporal patterns best reflect the latent compartments in our model. Both approach are available as R packages on CRAN.
Together, these methods provide powerful tools for integrating and selecting high-dimensional biological data in mechanistic modelling. They will be illustrated on examples of immune dynamics after vaccination for Varicella-Zoster virus and COVID-19.
Speakers:
| Speaker |
Biography |
Melanie Prague, INRIA Bordeaux Sud-Oest Center |
Melanie Prague is a permanent researcher at Inria (University of Bordeaux, France) and is the head of the SISTM team (Statistics in Immunology and translational medicine) since October 2016. Since 2013, she holds a PhD in Biostatistics and Public Health from the University of Bordeaux, France. She also was a postdoctoral fellow during almost three years at Harvard School of Public Health (Boston, USA). Her research focuses on the development of statistical methods for treatment and prevention of infectious diseases. She develops both within-host and between-host models to accelerate the development of treatments and vaccines. Her main fundings are centered around applications on HIV, Ebola, Nipah and COVID-19. |