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Multiomic prediction of therapeutic targets for human diseases associated with protein phase separation.
Lim, Christine M; González Díaz, Alicia; Fuxreiter, Monika; Pun, Frank W; Zhavoronkov, Alex; Vendruscolo, Michele.
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  • Lim CM; Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, United Kingdom.
  • González Díaz A; Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, United Kingdom.
  • Fuxreiter M; Department of Biomedical Sciences, University of Padova, Padova 35131, Italy.
  • Pun FW; Insilico Medicine, Hong Kong Science and Technology Park, Hong Kong, China.
  • Zhavoronkov A; Insilico Medicine, Hong Kong Science and Technology Park, Hong Kong, China.
  • Vendruscolo M; Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, United Kingdom.
Proc Natl Acad Sci U S A ; 120(40): e2300215120, 2023 10 03.
Article en En | MEDLINE | ID: mdl-37774095
The phenomenon of protein phase separation (PPS) underlies a wide range of cellular functions. Correspondingly, the dysregulation of the PPS process has been associated with numerous human diseases. To enable therapeutic interventions based on the regulation of this association, possible targets should be identified. For this purpose, we present an approach that combines the multiomic PandaOmics platform with the FuzDrop method to identify PPS-prone disease-associated proteins. Using this approach, we prioritize candidates with high PandaOmics and FuzDrop scores using a profiling method that accounts for a wide range of parameters relevant for disease mechanism and pharmacological intervention. We validate the differential phase separation behaviors of three predicted Alzheimer's disease targets (MARCKS, CAMKK2, and p62) in two cell models of this disease. Overall, the approach that we present generates a list of possible therapeutic targets for human diseases associated with the dysregulation of the PPS process.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Multiómica Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Multiómica Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos