High-throughput data-driven analysis of myofiber composition reveals muscle-specific disease and age-associated patterns

Contractile properties of myofibers are dictated by the abundance of myosin heavy chain (MyHC) isoforms. MyHC composition designates muscle function and its alterations could unravel differential muscle involvement in muscular dystrophies and aging. Current analyses are limited to visual assessments in which myofibers expressing multiple MyHC isoforms are prone to misclassifications. As a result, complex patterns and subtle alterations are unidentified. We developed a high-throughput data-driven myofiber analysis to quantitatively describe the variations in myofibers across the muscle. We investigated alterations in myofiber composition between genotypes, two muscles and two age groups. We show that this analysis facilitates the discovery of complex myofiber compositions and its dependency on age, muscle type and genetic conditions. ### Nonstandard abbreviations LGMD : Limb girdle muscular dystrophy MFI : mean fluorescence intensity MyHC : Myosin heavy chain SGCA-null : α-sarcoglycan-null SGCD-null : δ-sarcoglycan-null * ### Nonstandard abbreviations LGMD : Limb girdle muscular dystrophy MFI : mean fluorescence intensity MyHC : Myosin heavy chain SGCA-null : α-sarcoglycan-null SGCD-null : δ-sarcoglycan-null