dSCOPE: a software to detect sequences critical for liquid-liquid phase separation

Abstract

Membrane based cells are the fundamental structure and function units of organisms, while evidences were increasing that liquid-liquid phase separation (LLPS) is associated with the formation of membraneless organelles, such as P-bodies, nucleoli and stress granules. Many studies have been undertaken to explore the functions of protein phase separation, but these studies lacked an effective tool to identify the sequence segments that critical for LLPS (SCOPEs). In this study, we presented a novel software called dSCOPE (http://dscope.omicsbio.info) to predict the SCOPEs. To develop the predictor, we curated experimentally identified sequence segments that can drive LLPS from published literature. Then sliding sequence window based physiological, biochemical, structural and coding features were integrated by random forest algorithm to perform prediction. Through rigorous evaluation, dSCOPE was demonstrated to achieve satisfactory performance. Furthermore, large-scale analysis of human proteome based on dSCOPE showed that the predicted SCOPEs enriched various protein post-translational modifications and cancer mutations, and the proteins which contain predicted SCOPEs enriched critical cellular signaling pathways. Taken together, dSCOPE precisely predicted the protein sequence segments critical for LLPS, with various helpful information visualized in the webserver to facilitate LLPS related research.

Thermodynamic origins of two-component multiphase condensates of proteins

“…Recently, computer simulations have connected features of individual biomolecules to their phase behaviour. 73 Depending on the question being addressed, models from atomistic [74][75][76][77][78][79][80] via residue-level [81][82][83][84][85][86][87] to minimal, 80,[88][89][90] alongside other computational approaches such as predictive algorithms and machine-learning methods, [85][86][87][91][92][93][94][95] have all been used with success. Simple models for phase separation of multi-component mixtures and multiphase organisation have also been studied in detail with a combination of simulations and theory.…”

14-3-3 binding motif phosphorylation disrupts Hdac4-organized condensates to stimulate cardiac reprogramming

“…The condensate regulation of IDRs of Hdac4, MEF2C and Foxo1 were predicted by dSCOPE, which is a web server developed for detecting sequences critical for phase separation related proteins. 65 , 66 Predicted IDRs on Hdac4 were deleted respectively, and each truncated Hdac4 constructs were inserted into mammalian expression vector pMX. Each pMX plasmid was transformed into HEK293T cells to test the condensate formation of each truncated Hdac4 construct.…”

14-3-3 binding motif phosphorylation disrupts Hdac4 organized condensates to stimulate cardiac reprogramming

“…The condensate regulation of IDRs of Hdac4, MEF2C and Foxo1 were predicted by dSCOPE, which is a web server developed for detecting sequences critical for phase separation related proteins (61,62). Predicted IDRs on Hdac4 were deleted respectively, and each truncated Hdac4 constructs were inserted into mammalian expression vector pMX.…”