Computational Methods in Systems Biology: 20th International Conference, CMSB 2022, Bucharest, Romania, September 14–16, 2022, Proceedings (Lecture Notes in Computer Science, 13447)

This book constitutes the refereed proceedings of the 20th International Conference on Computational Methods in Systems Biology, CMSB 2022, held in Bucharest, Romania, in September 2022. The 13 full papers and 4 tool papers were carefully reviewed and selected from 43 submissions. CMSB focuses on modeling, simulation, analysis, design and control of biological systems. The papers are arranged thematically as follows: Chemical reaction networks; Boolean networks; continuous and hybrid models; machine learning; software. Preface Organization Invited Talks Targeting and Controlling Protein-Protein Interaction Networks in Disease Boolean Networks as a Link Between Knowledge, Data, and Quantitative Models How to Infer Accurate Gene Regulatory Networks From Gene Expression Sequence Space and Deep Learning to Better Understand Proteins GRO: A Multicell Bacterial Simulator Contents Chemical Reaction Networks Algebraic Biochemistry: A Framework for Analog Online Computation in Cells 1 Introduction 1.1 Related Work 2 Definitions and Main Theorem 2.1 Chemical Reaction Networks 2.2 Stabilization 2.3 Algebraic Curves and Algebraic Functions 3 Proof 4 Compilation Pipeline for Generating Stabilizing CRNs 4.1 Polynomialization 4.2 Stabilization 4.3 Quadratization 4.4 Lazy Dual-Rail Encoding 4.5 CRN Generation 5 Examples 6 Conclusion and Perspectives References Abstract Simulation of Reaction Networks via Boolean Networks 1 Introduction 2 Preliminaries 3 Arithmetic Expressions 4 Chemical Reaction Networks 5 First-Order Logic 6 Sign Abstraction of ODE Trajectories 7 Abstract Interpretation of ODEs 8 Boolean Networks with Non-deterministic Updates 9 Abstract Simulation of Reaction Networks 10 Thresholds 11 Application to Biomodel's Reaction Networks 12 Conclusion and Future Work References Abstraction-Based Segmental Simulation of Chemical Reaction Networks 1 Introduction 2 Preliminaries 3 The Plan: A Technical Overview 4 Segmental Simulation via Abstract States 4.1 Computing and Assembling Segments via Abstract States 4.2 Densely Concrete Simulations 4.3 Introduced Inaccuracy 5 From Segmental Simulations to Abstract Simulations 5.1 Segmental Abstraction of CTMC and Abstract Simulation 5.2 From Abstract Simulations Back to Concrete Predictions 6 Experimental Evaluation 7 Conclusion and Future Directions References Qualitative Dynamics of Chemical Reaction Networks: An Investigation Using Partial Tropical Equilibrations 1 Introduction 2 Definitions and Methods 2.1 Tropical Geometry Concepts 2.2 Partial Tropical Equilibrations and Slow-Fast Decompositions 2.3 Multiple Timescale Decompositions 2.4 Coarse Graining 3 Case Study: A Cell Cycle Model 3.1 Tropical Scaling of the Cell Cycle Model 3.2 Calculation of the Partial Tropical Equilibrations 3.3 Symbolic Dynamics by Tropicalization 3.4 Model Reduction Using Partial Tropical equilibrations 4 Conclusion and Future Work References Boolean Networks Prioritization of Candidate Genes Through Boolean Networks 1 Introduction 2 Methods 2.1 Reproducible Inference of a Cell-Line Specific Boolean Network 2.2 Detection of Master Regulators in a Specific Disease-Context 3 Results 3.1 Networks Obtained from the Inference Procedure 3.2 Recommended Master Regulator Candidates 4 Discussion A Building the Boolean Network A.1 State-of-the-Art in Boolean Network Inference A.2 Step (A): Building an Undirected Unsigned Graph A.3 Step (A): Gene Perturbation Experiments A.4 Step (B): Binarization of Experiments into Binary Profiles A.5 Step (B): Implementation of Topological Constraints A.6 Step (B): Implementation of Experimental Constraints A.7 Step (C): Inference Solutions and Model Selection B Summary of Tools in Network Identification C Robustness on a Larger Set of 50 Solutions D Tables D.1 Experimental Profiles From LINCS L1000 D.2 Parameters E Implementation of the Influence Maximization Algorithm E.1 Iteration of Attractor States E.2 Choice of Initial States F Additional Results References Variable Stabilisation in Boolean Monotonic Model Pools 1 Introduction 2 Preliminaries 3 Methods 3.1 Theory 3.2 Algorithms and Implementation 4 Results 5 Discussion References Variable-Depth Simulation of Most Permissive Boolean Networks 1 Introduction 2 Background 2.1 Boolean Networks and Dynamics 2.2 Sub-hypercubes and Closures 2.3 The Most Permissive Update Mode 3 Simulation Algorithm 3.1 Main Principle 3.2 Algorithm 3.3 Correctness, Complexity, and Parametrization 3.4 Sampling Reachable Attractors 4 Evaluation 4.1 Toy Examples 4.2 Models from Literature with Different Mutation Conditions 5 Discussion A Proofs A.1 Proof of Lemma 1 A.2 Proof of Lemma 2 References Minimal Trap Spaces of Logical Models are Maximal Siphons of Their Petri Net Encoding 1 Introduction 2 Preliminaries 2.1 Traps Spaces 2.2 Petri Net Encoding of Boolean Models 2.3 Siphons 3 Minimal Trap Spaces as Maximal Conflict-Free Siphons 4 Answer Set Programming-Based Method 5 Motivating Example 6 Evaluation 6.1 PyBoolNet Repository 6.2 Selected Models 7 Conclusion References Continuous and Hybrid Models Stability Versus Meta-stability in a Skin Microbiome Model 1 Introduction 2 Initial ODE Model with 13 Parameters 3 Using Published Experimental Data to Define Relations Between Model Parameters by Steady-State Reasoning 3.1 Parameter Values Inferred from Mono-culture Experiment Data 3.2 Parameter Relations Inferred from Experimental Data on AMP 3.3 Parameter Relations Inferred from Co-culture Data 4 Reduced Model with 5 Parameters 4.1 Simulations at the Time Scale of the Experiments 4.2 Parameter Sensitivity and Robustness Analyses 4.3 Meta-stability Revealed by Simulation on a Long Time Scale 5 Conditions Favoring the Pathogenic Population 5.1 Skin Surface pH Elevation 5.2 Reduced Production of Skin AMPs 6 Conclusion References Exact Linear Reduction for Rational Dynamical Systems 1 Introduction 2 Preliminaries and Prior Results 2.1 Preliminaries on Lumping 2.2 Overview of the CLUE Algorithm for Polynomial Dynamics ch10Ovchinnikov2020 3 Algorithm for Rational Dynamical Systems 3.1 Straightforward Extension of Algorithm 1 3.2 The Main Algorithm Based on Evaluation-Interpolation 3.3 Generating ``Sufficiently Many'' Evaluations 3.4 Improving the Efficiency of Algorithm 3 4 Implementation and Performance 4.1 Performance of Algorithm 3 4.2 Comparing Algorithm 2 and Algorithm 3 5 Examples 5.1 Michaelis-Menten Kinetics with Competing Substrates 5.2 Nerve Growth Factor Signaling 6 Conclusions References Limit Cycle Analysis of a Class of Hybrid Gene Regulatory Networks 1 Introduction 2 Hybrid Gene Regulatory Networks 3 Limit Cycle Analysis 3.1 Identification of Closed Trajectories 3.2 Stability Analysis 4 Application 4.1 HGRNs of Negative Feedback Loop in 3 Dimensions 4.2 HGRN of Cell Cycle in 5 Dimensions 5 Conclusion References Machine Learning Bayesian Learning of Effective Chemical Master Equations in Crowded Intracellular Conditions 1 Introduction 2 Connecting Different Mathematical Descriptions of Stochastic Kinetics Using Bayesian Optimization 2.1 Cellular Automata 2.2 The Chemical Master Equation and the SSA 2.3 Bayesian Optimisation 3 Applications 3.1 Michaelis-Menten Reaction in Crowded Conditions 3.2 Gene Network with Negative Feedback 4 Conclusions A Wasserstein Distance (WD) B CA Rules Modelling Enzyme Kinetics in Crowded Conditions C Supplementary Tables References Probabilistic Multivariate Early Warning Signals 1 Introduction 2 Methods 2.1 Autocorrelation Based EWS 2.2 The Probabilistic Time-Varying Vector Autoregressive-1 Process 2.3 Simulation Model 3 Results 3.1 Simulation Benchmark 3.2 Sensitivity Analysis 4 Discussion References Software MobsPy: A Meta-species Language for Chemical Reaction Networks 1 Introduction 2 MobsPy Syntax and Simulator 3 Genetic Circuits with MobsPy: The CRISPRlator 4 Conclusions A Comparison of Meta-reactions and Reactions for the Tree Model References Automated Generation of Conditional Moment Equations for Stochastic Reaction Networks 1 Introduction 2 Theory 3 Usage 4 Case Study 5 Discussion References An Extension of ERODE to Reduce Boolean Networks By Backward Boolean Equivalence 1 Introduction 2 Preliminaries 3 ERODE 4 An Illustration of BBE Reduction 5 Importing and Exporting Capabilities 6 Conclusion References eBCSgen 2.0: Modelling and Analysis of Regulated Rule-Based Systems 1 Introduction 2 Regulated Biochemical Space Language 3 Implementation 4 Evaluation 5 Conclusion References Author Index