ABSTRACT
Continued advances in variant effect prediction are necessary to demonstrate the ability of machine learning methods to accurately determine the clinical impact of variants of unknown significance (VUS). Towards this goal, the ARSA Critical Assessment of Genome Interpretation (CAGI) challenge was designed to characterize progress by utilizing 219 experimentally assayed missense VUS in the Arylsulfatase A (ARSA) gene to assess the performance of community-submitted predictions of variant functional effects. The challenge involved 15 teams, and evaluated additional predictions from established and recently released models. Notably, a model developed by participants of a genetics and coding bootcamp, trained with standard machine-learning tools in Python, demonstrated superior performance among submissions. Furthermore, the study observed that state-of-the-art deep learning methods provided small but statistically significant improvement in predictive performance compared to less elaborate techniques. These findings underscore the utility of variant effect prediction, and the potential for models trained with modest resources to accurately classify VUS in genetic and clinical research.
ABSTRACT
Age- and sex-related alterations in the control of multiple muscles during contractions are not well understood. The purpose of the present study was to examine the age and sex differences in force steadiness and intermuscular coherence (IMC), and thereby to clarify the functional role of IMC during plantar flexion. Twenty-six young (YNG, 23-34 years), thirty middle-aged (MID, 35-64 years) and twenty-four older adults (OLD, 65-82 years) performed submaximal isometric contractions of plantar flexion, while electromyography was recorded from the soleus (SOL), gastrocnemius lateralis/medialis (GL/GM) and tibialis anterior (TA) muscles. Coefficient of variation (CV) of torque and IMC in the alpha, beta and gamma bands was calculated. We found that OLD demonstrated significantly higher torque CV than YNG and MID, and males demonstrated significantly higher torque CV than females (both p < 0.05). The IMC in the gamma band (five out of the six pairs) was significantly higher in YNG than MID and/or OLD (p < 0.05), while the gamma band IMC between GL and SOL was significantly higher in females. However, age or sex differences were not detected in the alpha or beta band. Moreover, the gamma band IMC between SOL and TA had a weak (r = - 0.229) but significant (p < 0.05) negative correlation with torque CV. These results suggest that force steadiness differs with age and sex, and that the higher gamma band IMC may contribute to more stable force control during plantar flexion.
