Design of phase-separating biosystem via joint diffusion and positive-unlabeled guidance

Liquid-liquid phase separation (LLPS) is a widespread mechanism by which cells organize their internal environment, leading to the formation of membraneless organelles and biomolecular condensates. The ability to design to generate synthetic condensates properties has significant implications for biotechnology and medicine. While current studies focused on protein-driven phase separation, it is now clear that many condensates are multi-component systems, including proteins, DNA, and RNA. Hereby, We propose a joint diffusion framework that leverages the compositional generative process in and guide a joint generation with a positive-unlabeled (PU) assumption. Experiments on our newly curated multi-component phase separation dataset demonstrate the efficacy of generating unseen biosystems with desired phase behaviors. Our approach demonstrates the feasibility of \textit{in silico} designing and engineering multi-component phase-separating biosystems.