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Muscle project

The aim of the project is to develop a modular model describing physiological and biochemical processes in the human skeletal muscle and cardiovascular systems, regulation of gene expression at the skeletal muscle level under the influence of regular physical exercises in different modes. The development of such a mathematical model is based on the analysis, generalization and formalization of data from a large number of published and own experimental studies in the field of physiology and biochemistry of muscle activity and related fields. This approach turns the model into a kind of knowledge base, constantly expanding as it includes the mechanisms found in new studies and corrects the dependencies already existing in the model based on refined data. In order to build the integrative modular model, we have been using the original BioUML (https://ict.biouml.org/) software package developed by the authors of the project, which allows one to construct hierarchical modular models. This kind of models allows you to quickly adjust individual components of the model independently of each other. This approach makes it possible for a large number of experts and non-experts to work on the development and improvement of the model, and to create models of any level of details.

General scheme of the project

Experiments Rat Description of the experiment (Rat) GSE141827 Human Description of the experiment (Human) GSE164081

Bioinformatic analysis Human data analysis Differentially expressed genes Ontology analysis CAGE-seq analysis GTRD database Skeletal muscle specific signalling pathways Skeletal muscle specific signalling pathways in human TSS and DEGs Key master regulators of co-expressed genes Gene set enrichment analysis (GSEA) Unique intergenic TSS Alternative usage of dominating TSS Enhancers Merging CAGE experiments Methods References

Mathematical modelling Linkage of metabolic pathways and gene expression MetGeneConjugation Pathways and key proteins AMPK Ca-CaM-AMPK signaling models CaMKII CaMKKβ LKB1 SBGN diagrams Models Muscle models DataSets Models validation Working Notes Integrated modular models Integrated model description Integrated model validation Data availability for the manuscript

Publications of the project

• GTRD: a database on gene transcription regulation
• Modular Visual Model of Energy Metabolism in Human Skeletal Muscle
• A mathematical model linking signalling pathway and gene expression regulation in Human Skeletal Muscle
• Integrated Modular Model Linking Metabolism, Signaling Transduction and Gene Expression Regulation in Human Skeletal Muscle.
• Regulation of Proteins in Human Skeletal Muscle: The Role of Transcription
• Transcriptomic Signatures and Upstream Regulation in Human Skeletal Muscle Adapted to Disuse and Aerobic Exercise
• Genome-wide atlas of promoters expression reveals contribution of transcribed regulatory elements to genetic control of disuse-mediated atrophy of skeletal muscle
• A modular mathematical model of exercise-induced changes in metabolism, signaling, and gene expression in human skeletal muscle, IJMS

Our talks related to the project

• Mathematical modelling in the sport. Applications (in Russian). Alexander Vertyshev, All-Russian Conference "Day of the sport informatics", December, 3-4, 2021
• A modular mathematical model linking metabolic processes with gene expression regulation in human skeletal muscle at physical exercise (in Russian). Ilya Akberdin, All-Russian Conference "Day of the sport informatics", December, 3-4, 2021