Now, more than ever, pharmaceutical companies are relying on mathematical modeling & simulation to inform drug discovery and development decisions. In many cases, particularly for novel compounds, targets, and/or combinations, modelers must rely on incomplete data and/or extrapolation beyond existing data to address key questions, such as dose and dose regimen selection for clinical trials. In this talk, I will present a few case studies and related mathematical challenges that my team has faced and discuss why developing a better understanding of these problems is important in the context of drug discovery & development.
Methods for Biological Modeling Subgroup (MFBM)
MS01-MFBM: Mathematical Modeling Applied to Pharmaceutical Sciences Problems
Organized by: Carl Panetta (St. Jude Children's Research Hospital, US), Helen Moore (Laboratory for Systems Medicine, University of Florida, US)
- C.J. Musante (Pfizer, US) "A Few Open Mathematical Modeling Problems in Drug Discovery & Development"
- Jane Bai (FDA, US) "Conducting sensitivity analysis and uncertainty analysis for QSP needs more than mathematical computation"
- Freya Bachmann (Department of Mathematics and Statistics, University of Konstanz, Germany) "Computing the Individualized Optimal Drug Dosing Regimen Using Optimal Control"
- Tongli Zhang (Department of Pharmacology & Systems Physiology, College of Medicine, University of Cincinnati, US) "Coping with the Challenge of Heterogeneity with Integrated Modeling, Machine Learning, and Dynamical Analysis"
MS02-MFBM: Generalized Boolean network models and the concept of canalization
Organized by: Claus Kadelka (Iowa State University, United States) Note: this minisymposia has multiple sessions. The second session is MS03-MFBM.
- Gleb Pogudin (LIX, CNRS, Ecole Polytechnique, Institute Polytechnique de Paris, France) "Attractor stucture of Boolean networks of small canalizing depth"
- S. S. Ravi (Biocomplexity Institute & Initiative, University of Virginia, and Department of Computer Science, University at Albany, United States) "Efficient Algorithms for Boolean Nested Canalyzing Functions"
- Daniel Rosenkrantz (Biocomplexity Institute & Initiative, University of Virginia, and Department of Computer Science, University at Albany, United States) "Testing Phase Space Properties of Synchronous Dynamical Systems with Nested Canalyzing Local Functions: Complexity Results and Algorithms"
- Matthew Wheeler (Department of Medicine, University of Florida, United States) "Reducibility of Boolean Networks: Toward a Theory of Modularity"
MS03-MFBM: Generalized Boolean network models and the concept of canalization
Organized by: Claus Kadelka (Iowa State University, United States) Note: this minisymposia has multiple sessions. The second session is MS02-MFBM.
- Claus Kadelka (Iowa State University, United States) "Collective canalization"
- Elena Dimitrova (California Polytechnic State University, United States) "Revealing the canalizing structure of Boolean functions — algorithms and applications"
- Matthew Macauley (Clemson University, United States) "Toggling independent sets as an asynchronous Boolean network"
- Alan Veliz-Cuba (University of Dayton, Ohio, United States) "Identification of control targets in Boolean networks via computational algebra"
MS06-MFBM: Mathematical and computational methods to augment the reliability of biological models for better decision-making
Organized by: Vincent Lemaire (Genentech, CA, USA, United States), Khamir Mehta (Amgen, Inc, United States), Malidi Ahamadi (Amgen, CA, United States)
- Chris Rackauckas (MIT and Pumas AI, MA, USA, United States) "Accelerating Quantitative Systems Pharmacology with Machine Learning"
- Oleg Demin Jr (InSysBio, Russia) "Implementation of variability or uncertainty in parameter values to validate QSP models."
- Gianluca Selvaggio (Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI), Italy) "Parameter free approaches in QSP: modelling the cytokine release following bispecific T-cell engager therapy"
- Sietse Braakman (AbbVie Inc., Quantitative Translational Modeling Group, United States) "A framework for the evaluation of QSP models, with a focus on verification, validation and uncertainty quantification (VVUQ) methods"
MS07-MFBM: From Machine Learning to Deep Learning Methods in Biology
Organized by: Erica Rutter (University of California, Merced, United States), Suzanne Sindi (University of California, Merced, United States) Note: this minisymposia has multiple sessions. The second session is MS08-MFBM.
- Emilia Kozlowska (Departement of Systems Biology and Engineering, Silesian University of Technology, Poland) "Application of mechanistic and machine learning modeling to predict long-term response to treatment for cancer patients"
- Sara Ranjbar (Mathematical NeuroOncology Lab, Precision Neurotherapeutics Program, Mayo Clinic, Arizona, United States) "MRI-based estimation of the abundance of immunohistochemistry markers in GBM brain using deep learning"
- Joan Ponce (UCLA, United States) "An integrated framework for building trustworthy data-driven epidemiological models: Application to the COVID-19 outbreak in New York City"
- Emily Zhang (North Carolina State University, USA) "Deep Learning and Regression Approaches to Forecasting Blood Glucose Levels for Type 1 Diabetes"
MS08-MFBM: From Machine Learning to Deep Learning Methods in Biology
Organized by: Erica Rutter (University of California, Merced, United States), Suzanne Sindi (University of California, Merced, United States) Note: this minisymposia has multiple sessions. The second session is MS07-MFBM.
- Ali Heydari ((i) UC Merced Department of Applied Mathematics and (ii) Health Sciences Research Institute at UC Merced, USA) "Deep Generative Models for Realistic Single-Cell RNA-Seq Data Augmentation"
- Mohammad Jafari (Postdoctoral Scholar, Department of Applied Mathematics Jack Baskin School of Engineering University of California, Santa Cruz, USA) "Machine Learning-based Feedback Controller for Directing Stem Cell Membrane Potential"
- Thomas de Mondesir (Université Claude Bernard Lyon 1 & UC Merced, France) "Generating biological images to train deep-learning-based segmentation models"
- Jordan Collignon (University of California, Merced, USA) "A High-throughput Pipeline for Analyzing Experimental Images of Sectored Yeast Colonies"
MS09-MFBM: Emergent behavior across scales: locomotion, mixing, and collective motion in active swimmers
Organized by: Robert Guy (University of California Davis, United States), Arvind Gopinath (University of California Merced, United States) Note: this minisymposia has multiple sessions. The second session is MS15-MFBM.
- Henry Fu (University of Utah, United States) "Symmetry breaking propulsion of magnetically rotated spheres in nonlinearly viscoelastic fluids"
- Kathryn Link (University of California Davis, United States) "Emergent Properties of Flagellar Waveforms in Viscoelastic Fluids"
- Rudi Schuech (Tulane University, United States) "Viscoelastic Network Remodeling by Microswimmers"
- Sookkyung Lim (University of Cincinnati, United States) "Simulations of microswimmers propelled by multiple flagella"
MS11-MFBM: Stochastic Systems Biology: Theory and Simulation
Organized by: Jae Kyoung Kim (Department of Mathematical Sciences, KAIST, Republic of Korea), Ramon Grima (University of Edinburgh, United Kingdom) Note: this minisymposia has multiple sessions. The second session is MS12-MFBM.
- Zhixing Gao (Key Laboratory of Advanced Control and Optimization for Chemical Processes, Ministry of Education, East China University of Science and Technology, China) "Neural network aided approximation and parameter inference of stochastic models of gene expression"
- Abhyudai Singh (University of Delaware, USA) "Modeling stochasticity in timing of intracellular events: A first-passage time approach"
- Thomas Prescott (Alan Turing Institute, United Kingdom) "Learning a multifidelity simulation strategy for likelihood-free Bayesian inference."
- Ruben Perez-Carrasco ( Imperial College London, United Kingdom) "Should we care about cell cycle variability when studying stochastic gene expression?"
MS12-MFBM: Stochastic Systems Biology: Theory and Simulation
Organized by: Jae Kyoung Kim (Department of Mathematical Sciences, KAIST, Republic of Korea), Ramon Grima (University of Edinburgh, United Kingdom) Note: this minisymposia has multiple sessions. The second session is MS11-MFBM.
- Hyukpyo Hong (Department of Mathematical Sciences, KAIST, Republic of Korea) "Inference of stochastic dynamics in biochemical reaction networks by exploiting deterministic dynamics"
- Zhou Fang (ETH Zurich, Switzerland) " Stochastic filtering for multiscale stochastic reaction networks based on hybrid approximations"
- Samuel Isaacson (Boston University, Department of Mathematics and Statistics, USA) "Stochastic Reaction-Drift-Diffusion Methods for Studying Cell Signaling"
- Brian Munsky (Colorado State University, USA) "Designing Optimal Microscopy Experiments to Harvest Single-Cell Fluctuation Information while Rejecting Image Distortion Effects"
MS13-MFBM: Data-driven methods for biological modeling in industry
Organized by: Kevin Flores (North Carolina State University, USA) Note: this minisymposia has multiple sessions. The second session is MS14-MFBM.
- Anna Sher (Pfizer, USA) "Quantitative Systems Pharmacology (QSP) in cardiovascular disease: Preclinical case studies with real-world data"
- Doris Fuertinger (Fresenius Medical Care, Germany) "1 year of precision therapy: Experiences in optimal drug administration based on an individualized biomathematical anemia model"
- Alhaji Cherif (Renal Research Institute, USA) "Bone and mineral disturbances in uremic patients"
- Malidi Ahamadi (Amgen, USA) "Disease progression platform for Leucine-Rich Repeat Kinase 2 in Parkinson's Disease to Inform Clinical Trial Designs"
MS14-MFBM: Data-driven methods for biological modeling in industry
Organized by: Kevin Flores (North Carolina State University, USA) Note: this minisymposia has multiple sessions. The second session is MS13-MFBM.
- Richard Allen (Quantitative Systems Pharmacology, Early Clinical Development, Pfizer Worldwide Research Development and Medical, USA) "Analyzing and Predicting Clinical Trial Data with Systems Modeling"
- Florencio Serrano Castillo (Clinical Pharmacology, Modelling and Simulations, Amgen Inc., USA) "Dosing guidance optimization, leveraging real world heterogeneity to forecast clinical biomarker response"
- Zackary Kenz (DILIsym Services, a Simulations Plus Company, USA) "Quantitative Systems Pharmacology Modeling of Fibrotic Diseases"
- Anna Neely (TigerRisk Partners, USA) "Estimating the growing risk of severe thunderstorms"
MS15-MFBM: Emergent behavior across scales: locomotion, mixing, and collective motion in active swimmers
Organized by: Robert Guy (University of California Davis, United States), Arvind Gopinath (University of California Merced, United States) Note: this minisymposia has multiple sessions. The second session is MS09-MFBM.
- Maxime Theillard (University of California Merced, United States) "Multi-scale multi-species modeling of emergent flows and active mixing in confined bacterial swarms"
- Paulo Arratia (University of Pennsylvania, United States) "Bacteria hinder stretching and large-scale transport in time-periodic flows"
- Bin Liu (University of California Merced, United States) "Anomalous size-dependent active transport in structured environments"
- Nick Cogan (Florida State University, United States) "Modeling the Origin of Life Reaction in Microfluidic Chambers"
MS18-MFBM: Mechanical Models of Complex Diseases
Organized by: Fabian Spill (University of Birmingham, USA)
- Vijay Rajagopal (University of Melbourne, Australia) "Surface area-to-volume ratio, not cellular viscoelasticity is the major determinant of red blood cell traversal through small channels."
- Bindi Brook (University of Nottingham, UK) "Inflammation driven mechanical model of asthmatic airway remodelling"
- Herbert Levine (Northeastern University, USA) "The role of extracellular matrix in motility and metastasis"
- Stephanie Fraley (University of California San Diego, USA) "A spatial model of YAP/TAZ mechanotransduction reveals new insights into how cells sense ECM dimensionality"
MS19-MFBM: Algebra, Combinatorics, and Topology in Modern Biology
Organized by: Daniel Cruz (Georgia Institute of Technology, U.S.), Margherita Maria Ferrari (University of South Florida, U.S.) Note: this minisymposia has multiple sessions. The second session is MS20-MFBM.
- Margherita Maria Ferrari (University of South Florida, U.S.) "Formal grammar modeling three-stranded DNA:RNA braids"
- Svetlana Poznanovic (Clemson University, U.S.) "Using Polytopes to Improve RNA Branching Predictions"
- Chad Giusti (University of Delaware, U.S.) "Comparing Topological Feature Coding Across Neural Populations"
- Abdulmelik Mohammed (University of South Florida, U.S.) "Topological Eulerian Circuits for the Design of DNA Nanostructures"
MS20-MFBM: Algebra, Combinatorics, and Topology in Modern Biology
Organized by: Daniel Cruz (Georgia Institute of Technology, U.S.), Margherita Maria Ferrari (University of South Florida, U.S.) Note: this minisymposia has multiple sessions. The second session is MS19-MFBM.
- Mustafa Hajij (Santa Clara University, U.S.) "TDA-Net: Fusion of Persistent Homology and Deep Learning Features for COVID-19 Detection in Chest X-Ray Images"
- Hector Banos (Dalhousie University, Canada) "Identifiability of Species Network Topologies from Genomic Sequences"
- Nida Obatake (Texas A&M University, U.S.) "Mixed Volume of Chemical Reaction Networks"
- Raina Robeva (Randolph-Macon College, U.S.) "Algebraic Biology in the Curriculum"
Sub-group contributed talks
CT01-MFBM: MFBM Subgroup Contributed Talks
- Wayne Hayes UC Irvine "The One True Way to use GO terms to evaluate Network Alignments"
- Giulia Palermo UCR "Harnessing graph theory to decrypt the allosteric mecahnism in CRISPR-Cas9"
- Dennis Manjaly Joshy UC Santa Barbara "A Koopman Operator Approach for Genetic Circuit Design"
- Ying Zhang Brandeis University "Immersed Boundary Simulations of Red Blood Cells Near Vessel Walls"
CT02-MFBM: MFBM Subgroup Contributed Talks
- Yifei Li Queensland University of Technology "Travelling waves in nonlinear reaction-diffusion equations"
- Juan Carlo Flores Mallari Ateneo de Manila University, Nara Institute of Science and Technology "Modeling Collective Behavior of Passengers Boarding and Disembarking from Public Transport in the Philippines"
- Leo Diaz University of Melbourne "Hypergraphs as a tool for automated and reproducible modelling of biochemical systems"
- Shawn Means Massey University "A Permutation Method to Assemble Networks"
CT03-MFBM: MFBM Subgroup Contributed Talks
- Gregory Szep King's College London "Parameter Inference with Bifurcation Diagrams"
- Sta Léa University of Leeds, United Kingdom " IL-7R mathematical modelling: algebraic expressions for amplitude and EC50"
- Johannes Borgqvist Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford "Symmetry methods for model-construction and analysis in the context of collective cell migration"
- Remus Stana University of Leeds "Diffusion in a domain with inclusion"
CT04-MFBM: MFBM Subgroup Contributed Talks
- Elizabeth Trofimenkoff University of Lethbridge "An algorithm for obtaining parametric conditions for the validity of the steady-state approximation"
- Alexander D. Kaiser Stanford University "Design-based models of heart valves and bicuspid aortic valve flows"
- Jay Stotsky University of Minnesota "The Impact of Cell-Level Details on Tissue-Scale Properties"
- Fawaz K Alalhareth The University of Texas at Arlington "Higher-Order Modified Nonstandard FiniteDifference Methods for Dynamical Systems in Biology"
CT05-MFBM: MFBM Subgroup Contributed Talks
- Fatemeh Sadat Fatemi Nasrollahi Pennsylvania State University "Attractor identification method based on generalized positive feedback loops and their functional relationships"
- Megan Coomer Melbourne University "Shaping the Epigenetic Landscape: Complexities and Consequences"
- Kumar Saurabh National Taiwan University "MATHEMATICAL MODELING OF ION CHANNEL FLOW WITHIN CONTINUUM FRAMEWORK"
- Nayana Wanasingha Department of Mathematical Sciences, University of Cincinnati "Molecular mechanisms regulating frequecy demultiplication of circadian rhythms in Neurospora Crassa"
CT06-MFBM: MFBM Subgroup Contributed Talks
- Miroslav Phan ETH Zurich, Department of Biosystems Science and Engineering, Basel, Switzerland "A Rejection Based Gillespie Algorithm for non-Markovian Stochastic Processes with Individual Reactant Properties"
- Elba Raimundez University of Bonn "Efficient sampling by marginalization of scaling parameters for mechanistic models with relative data"
- Aden Forrow Mathematical Institute, University of Oxford "Learning stochastic dynamics with measurement noise"
- Marco Berghoff Karlsruhe Institute of Technology "Cells In Sillico â€“ Parallel Tissue Development Simulation"
CT07-MFBM: MFBM Subgroup Contributed Talks
- Eli Newby The Pennsylvania State University " Identifying Driver Nodes in Biological Networks using Subsets of the Feedback Vertex Set"
- Xiaoyu Duan University of Pittsburgh "Parameter identification of linear-in-parameters systems from a single trajectory"
- Katherine Pearce Department of Mathematics, North Carolina State University "Modeling and parameter subset selection for fibrin polymerization kinetics with applications to wound healing"
- Yue Liu University of Oxford "Organisation of diffusion-driven stripe formation in expanding domains"
CT09-MFBM: MFBM Subgroup Contributed Talks
- Ivan Borisov INSYSBIO LLC "Constrained Optimization Approach to Predictability Analysis in Bio-Mathematical Modeling"
- Anna Molyavko ICM SB RAS, Krasnoyarsk Mathematical Center "Novel alignment-free highly parallel method to compare symbol sequences of an arbitrary length"
- Dimitrios Patsatzis National Technical University of Athens "Towards extending the arsenal of cancer immunology modeling with algorithmic asymptotic analysis"
- Viktoriia Fedotovskaia Siberian federal university, Institute of fundamental biology and biotechnology "The prevalence of function over taxonomy for triplet composition of mitochondrial and chloroplast plant genes"
Sub-group poster presentations
MFBM-2 (Session: PS02) Samarth Kadaba University of California, Santa Barbara "Discovering Sequence-Activity Relationships using Machine Learning: Convolutional Neural Networks (CNNs) and Gaussian Process Regressions (GPRs)."
MFBM-4 (Session: PS02) Alex John Quijano University of California Merced "Evolving Contextual Semantics"
MFBM-7 (Session: PS05) Veronika Musatova INSYSBIO "Unified approach for in vitro data based parameters estimation"
MFBM-9 (Session: PS05) Yun Min Song Korea Advanced Institute of Science and Technology "Universally valid reduction of multiscale stochastic biochemical systems with simple non-elementary propensities"