catGRANULE 2.0: accurate predictions of liquid-liquid phase separating proteins at single amino acid resolution

IF 10.1 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Genome Biology Pub Date : 2025-02-20 DOI:10.1186/s13059-025-03497-7
Michele Monti, Jonathan Fiorentino, Dimitrios Miltiadis-Vrachnos, Giorgio Bini, Tiziana Cotrufo, Natalia Sanchez de Groot, Alexandros Armaos, Gian Gaetano Tartaglia
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Abstract

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 .
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液-液相分离(LLPS)可形成无膜细胞器,这对细胞组织至关重要,并与疾病有关。我们介绍了 catGRANULE 2.0 ROBOT,这是一种整合了物理化学特性和 AlphaFold 衍生结构特征的算法,可在单氨基酸分辨率下预测 LLPS。该方法性能高,能可靠地评估突变对 LLPS 倾向的影响,详细预测特定突变如何增强或抑制相分离。在包括显微镜数据在内的实验验证的支持下,该方法预测了不同生物体和细胞区的 LLPS,为 LLPS 机制和突变影响提供了宝贵的见解。该工具可在 https://tools.tartaglialab.com/catgranule2 和 https://doi.org/10.5281/zenodo.14205831 免费获取。
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来源期刊
Genome Biology
Genome Biology Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
21.00
自引率
3.30%
发文量
241
审稿时长
2 months
期刊介绍: Genome Biology stands as a premier platform for exceptional research across all domains of biology and biomedicine, explored through a genomic and post-genomic lens. With an impressive impact factor of 12.3 (2022),* the journal secures its position as the 3rd-ranked research journal in the Genetics and Heredity category and the 2nd-ranked research journal in the Biotechnology and Applied Microbiology category by Thomson Reuters. Notably, Genome Biology holds the distinction of being the highest-ranked open-access journal in this category. Our dedicated team of highly trained in-house Editors collaborates closely with our esteemed Editorial Board of international experts, ensuring the journal remains on the forefront of scientific advances and community standards. Regular engagement with researchers at conferences and institute visits underscores our commitment to staying abreast of the latest developments in the field.
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