TY - JOUR
T1 - catGRANULE 2.0: accurate predictions of liquid-liquid phase separating proteins at single amino acid resolution
AU - Monti, Michele
AU - Fiorentino, Jonathan
AU - Miltiadis-Vrachnos, Dimitrios
AU - Bini, Giorgio
AU - Cotrufo, Tiziana
AU - Sanchez de Groot, Natalia
AU - Armaos, Alexandros
AU - Tartaglia, Gian Gaetano
PY - 2025/2/20
Y1 - 2025/2/20
N2 - Liquid-liquid phase separation (LLPS) enables the formation of membraneless organelles, essential for cellular organization and implicated in diseases. We introduce catGRANULE 2.0 ROBOT, an algorithm integrating physicochemical properties and AlphaFold-derived structural features to predict LLPS at single-amino-acid resolution. The method achieves high performance and reliably evaluates mutation effects on LLPS propensity, providing detailed predictions of how specific mutations enhance or inhibit phase separation. Supported by experimental validations, including microscopy data, it predicts LLPS across diverse organisms and cellular compartments, offering valuable insights into LLPS mechanisms and mutational impacts. The tool is freely available at https://tools.tartaglialab.com/catgranule2 and https://doi.org/10.5281/zenodo.14205831.
AB - Liquid-liquid phase separation (LLPS) enables the formation of membraneless organelles, essential for cellular organization and implicated in diseases. We introduce catGRANULE 2.0 ROBOT, an algorithm integrating physicochemical properties and AlphaFold-derived structural features to predict LLPS at single-amino-acid resolution. The method achieves high performance and reliably evaluates mutation effects on LLPS propensity, providing detailed predictions of how specific mutations enhance or inhibit phase separation. Supported by experimental validations, including microscopy data, it predicts LLPS across diverse organisms and cellular compartments, offering valuable insights into LLPS mechanisms and mutational impacts. The tool is freely available at https://tools.tartaglialab.com/catgranule2 and https://doi.org/10.5281/zenodo.14205831.
KW - Liquid-liquid phase separation
KW - Machine learning
KW - Mutations
KW - Protein features
KW - Subcellular compartmentalization
UR - https://www.scopus.com/pages/publications/85219222177
UR - https://www.mendeley.com/catalogue/00bc47c0-a860-3d71-b677-4cf7325110ef/
U2 - 10.1186/s13059-025-03497-7
DO - 10.1186/s13059-025-03497-7
M3 - Article
C2 - 39979996
SN - 1474-760X
VL - 26
SP - 33
JO - Genome Biology
JF - Genome Biology
IS - 1
M1 - 33
ER -