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Comprehensive SHAP Values and Single-Cell Sequencing Technology Reveal Key Cell Clusters in Bovine Skeletal Muscle

Yaqiang Guo,Fengying Ma,Peipei Li,Lili Guo,Zaixia Liu,Chenxi Huo,C. Shi,Lin Zhu,Mingjuan Gu,Risu Na,Wenguang Zhang

Published 2025 in International Journal of Molecular Sciences

ABSTRACT

The skeletal muscle of cattle is the main component of their muscular system, responsible for supporting and movement functions. However, there are still many unknown areas regarding the ranking of the importance of different types of cell populations within it. This study conducted in-depth research and made a series of significant findings. First, we trained 15 bovine skeletal muscle models and selected the best-performing model as the initial model. Based on the SHAP (Shapley Additive exPlanations) analysis of this initial model, we obtained the SHAP values of 476 important genes. Using the contributions of these 476 genes, we reconstructed a 476-gene SHAP value matrix, and relying solely on the interactions among these 476 genes, successfully mapped the single-cell atlas of bovine skeletal muscle. After retraining the model and further interpretation, we found that Myofiber cells are the most representative cell type in bovine skeletal muscle, followed by neutrophils. By determining the key genes of each cell type through SHAP values, we conducted analyses on the correlations among key genes and between cells for Myofiber cells, revealing the critical role these genes play in muscle growth and development. Further, by using protein language models, we performed cross-species comparisons between cattle and pigs, deepening our understanding of Myofiber cells as key cells in skeletal muscle, and exploring the common regulatory mechanisms of muscle development across species.

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