Structure-independent machine-learning predictions of the CDK12 interactome.

Cyclin-dependent kinase 12 (CDK12) is a critical regulatory protein involved in transcription and DNA repair processes. Dysregulation of CDK12 has been implicated in various diseases, including cancer. Understanding the CDK12 interactome is pivotal for elucidating its functional roles and potential therapeutic targets. Traditional methods for interactome prediction often rely on protein structure information, limiting applicability to CDK12 characterized by partly disordered terminal C region. In this study, we present a structure-independent machine-learning model that utilizes proteins' sequence and functional data to predict the CDK12 interactome. This approach is motivated by the disordered character of the CDK12 C-terminal region mitigating a structure-driven search for binding partners. Our approach incorporates multiple data sources, including protein-protein interaction networks, functional annotations, and sequence-based features, to construct a comprehensive CDK12 interactome prediction model. The ability to predict CDK12 interactions without relying on structural information is a significant advancement, as many potential interaction partners may lack crystallographic data. In conclusion, our structure-independent machine-learning model presents a powerful tool for predicting the CDK12 interactome and holds promise in advancing our understanding of CDK12 biology, identifying potential therapeutic targets, and facilitating precision-medicine approaches for CDK12-associated diseases.