Identification of Phase Separating Proteins With Distributed Reduced Alphabet Representations of Sequences

Phase separation of proteins play key roles in cellular physiology including bacterial division, tumorigenesis etc. Consequently, understanding the molecular forces that drive phase separation has gained considerable attention and several factors including hydrophobicity, protein dynamics, etc., have been implicated in phase separation. Data-driven identification of new phase separating proteins can enable in-depth understanding of cellular physiology and may pave way towards developing novel methods of tackling disease progression. In this work, we exploit the existing wealth of data on phase separating proteins to develop sequence-based machine learning method for prediction of phase separating proteins. We use reduced alphabet schemes based on hydrophobicity and conformational similarity along with distributed representation of protein sequences and biochemical properties as input features to Support Vector Machine (SVM) and Random Forest (RF) machine learning algorithms. We used both curated and balanced dataset for building the models. RF trained on balanced dataset with hydropathy, conformational similarity embeddings and biochemical properties achieved accuracy of 97%. Our work highlights the use of conformational similarity, a feature that reflects amino acid flexibility, and hydrophobicity for predicting phase separating proteins. Use of such "interpretable" features obtained from the ever-growing knowledgebase of phase separation is likely to improve prediction performances further.