A comprehensive BIAPSS platform for the physicochemical featurization of phase separating proteins

The liquid-liquid phase separation (LLPS) of biological macromolecules has emerged as a foundational mechanism underlying the formation of a myriad of membraneless organelles (MLOs), such as stress granules, transcription factor condensates, and chromatin compartments. A molecular grammar of sequences, which would enable a quantitative prediction and understanding of protein phase separation from first principles is currently missing. A major challenge in the field is the sparsity of bioinformatics data and the lack of computational, data-driven tools for biophysical and statistical analysis of proteins capable of phase separation. Here we present the utility of web applications framed within a novel open-source platform for BioInformatic Analysis of liquid-liquid Phase-Separating protein Sequences, https://biapss.chem.iastate.edu/. BIAPSS combines high-throughput interactive data analytics of physicochemical and evolutionary features with a comprehensive repository of bioinformatic data for on-the-fly research of the sequence-dependent properties of proteins with known LLPS behavior. To facilitate exploration of the services and provide the interpretation guideline, we present two attention-getting case studies of FUS and hnRNPDL. This should help the LLPS community uncover the nature of interactions driving the formation of membraneless organelles.