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.
Scientific Meetings
Integrating large- to high-dimension data in mechanistic model: Application to modeling response to vaccination?
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.
Training Courses
Integrating large- to high-dimension data in mechanistic model: Application to modeling response to vaccination?
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.
Journal Club
Integrating large- to high-dimension data in mechanistic model: Application to modeling response to vaccination?
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.
Webinars
Integrating large- to high-dimension data in mechanistic model: Application to modeling response to vaccination?
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.
Careers Meetings
Integrating large- to high-dimension data in mechanistic model: Application to modeling response to vaccination?
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.
Upcoming Events
PSI Introduction to Industry Training (ITIT) Course - 2026/2027
An introductory course giving an overview of the pharmaceutical industry and the drug development process as a whole, aimed at those with 1-3 years' experience. It comprises of six 2-day sessions covering a range of topics including Research and Development, Toxicology, Data Management and the Role of a CRO, Clinical Trials, Reimbursement, and Marketing.
Joint PSI/EFSPI Visualisation SIG 'Wonderful Wednesday' Webinars
Our monthly webinar explores examples of innovative data visualisations relevant to our day to day work. Each month a new dataset is provided from a clinical trial or other relevant example, and participants are invited to submit a graphic that communicates interesting and relevant characteristics of the data.
Enhancing Clinical Study Reporting with the Estimand Framework
Join us for an insightful webinar where we explore practical strategies for applying the estimand framework in clinical study reporting. Drawing on real-world experiences and case studies, we will share recommendations to help you:
• Understand the role of estimands in improving transparency and interpretation of trial results.
• Navigate common challenges in implementing the framework during reporting.
• Apply best practices to enhance regulatory submissions, webposting in public registries (clinicaltrials.gov/CTIS), and scientific publications.
Whether you are involved in clinical trial design, data analysis, or regulatory submissions, this session will provide actionable guidance to realize the full potential of the estimand framework.
The Book Club session will discuss a podcast episode where the host of the Power Hour, Adrienne Herbert, chats with Ros about his book, and the secrets that he learned from years of working in high-pressure newsrooms, and the ten elements of a good explanation and the seven steps you need to take to express yourself with clarity and impact.
Our monthly webinar series allows attendees to gain practical knowledge and skills in open-source coding and tools, with a focus on applications in the pharmaceutical industry. This month’s session, “Graphics Basics,” will introduce the fundamentals of producing graphics using the ggplot2 package.
Connecting the False Discovery Rate to Shrunk Estimates
A 1 hour online event, that includes a presentation followed by Q&A.
This talk will explore the “replication crisis” in science, focusing on how testing large numbers of hypotheses can lead to false positive findings. It introduces key statistical approaches—False Discovery Rate (FDR) and shrinkage methods—to address this issue, and explains their conceptual foundations and connections. The session will also highlight how these tools can be understood within an empirical-Bayesian framework, linking significance testing with effect size estimation.
This networking event is aimed at statisticians that are new to the pharmaceutical industry who wish to meet colleagues from different companies and backgrounds.
PSI Book Club: The AI Con – Joint with ASA Book Club
The Guardian described the authors of this book as refreshingly sarcastic! What is sold to us as AI, they announce, is just "a bill of goods": "A few major well-placed players are poised to accumulate significant wealth by extracting value from other people's creative work, personal data, or labour, and replacing quality services with artificial facsimiles."
PSI Book Club: Another Door Opens – Book Club Special Event
This is a Book Club Special Event in response to the changes in our industry and as a supportive move to create community and connection for those navigating redundancy and uncertainty. Read the book in advance of the book club session then join the zoom call to discuss ideas. There will be breakout groups to connect with others, exchange experiences of how the book has helped, and offer support.
This networking event is aimed at statisticians that are new to the pharmaceutical industry who wish to meet colleagues from different companies and backgrounds.
This networking event is aimed at statisticians that are new to the pharmaceutical industry who wish to meet colleagues from different companies and backgrounds.
GSK - Statistics Director - Vaccines and Infectious Disease
We are seeking an experienced and visionary Statistics Director to join our Team and lead strategic statistical innovation across GSK’s Vaccines and Infectious Disease portfolio.
As a Senior Biostatistician I at ICON, you will play a pivotal role in designing and analyzing clinical trials, interpreting complex medical data, and contributing to the advancement of innovative treatments and therapies.
As a Statistical Programmer II at ICON, you will play a vital role in the development, validation, and execution of statistical programs to support clinical trial analysis and reporting.
As a Statistical Scientist at ICON, you will play a pivotal role in designing and analyzing clinical trials, interpreting complex medical data, and contributing to the advancement of innovative treatments and therapies.
We have an exciting opportunity for an Associate Director, Biostatistics to join a passionate team within Advanced Quantitative Sciences – Full Development.
: We have an exciting opportunity for an Associate Director (AD), Statistical Programming, to join a passionate team within Advanced Quantitative Sciences- Development.
Novartis - Senior Principal Statistical Programmer
We have an exciting opportunity for a Senior Principal Statistical Programmer, to join a passionate team within Advanced Quantitative Sciences – Development.
Pierre Fabre - Clinical Development Safety Statistics Expert M/F
We are seeking a highly skilled and proactive Clinical Development Safety Statistics Expert to join our Biometry Department and the Biometry Leadership Team based in Toulouse (31, Oncopole) or Boulogne (92).
Pierre Fabre - Lead Statistician – Real World Evidence -CDI- M/F
Pierre Fabre Laboratories are hiring a highly skilled and experienced Lead Statistician – Real World Evidence (RWE) to join the Biometry Department, part of the Data Science & Biometry Department, based in Toulouse (Oncopôle) or Boulogne.
Pierre Fabre - Lead Statistician- Clinical Trials M/F
We are seeking a highly skilled and experienced Lead Statistician in Clinical Trials to join our Biometry Department based in Toulouse (31, Oncopole) or Boulogne (92).
As a Senior Statistician at Viatris, you will take a leading role in designing clinical studies, guiding statistical strategy, and ensuring that statistical deliverables meet the highest scientific and regulatory standards.