PMID- 34188175 OWN - NLM STAT- MEDLINE VI - 4 IP - 1 TI - A Bayesian semi-parametric model for thermal proteome profiling. PG - 810 LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Commun Biol JT - Communications biology JID - 101719179 IS - 2399-3642 (Electronic) LID - 10.1038/s42003-021-02306-8 [doi] FAU - Fang, Siqi AU - Fang S AD - Cambridge Centre for Proteomics, Department of Biochemistry, University of Cambridge, Cambridge, UK. AD - Milner Therapeutics Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK. FAU - Kirk, Paul D W AU - Kirk PDW AD - MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK. AD - Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK. FAU - Bantscheff, Marcus AU - Bantscheff M AUID- ORCID: http://orcid.org/0000-0002-8343-8977 AD - Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany. FAU - Lilley, Kathryn S AU - Lilley KS AUID- ORCID: http://orcid.org/0000-0003-0594-6543 AD - Cambridge Centre for Proteomics, Department of Biochemistry, University of Cambridge, Cambridge, UK. ksl23@cam.ac.uk. AD - Milner Therapeutics Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK. ksl23@cam.ac.uk. FAU - Crook, Oliver M AU - Crook OM AUID- ORCID: http://orcid.org/0000-0001-5669-8506 AD - Cambridge Centre for Proteomics, Department of Biochemistry, University of Cambridge, Cambridge, UK. omc25@cam.ac.uk. AD - MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK. omc25@cam.ac.uk. AD - Milner Therapeutics Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK. omc25@cam.ac.uk. IS - 2399-3642 (Linking) RN - 0 (Proteome) SB - IM MH - *Bayes Theorem MH - *Protein Stability MH - *Proteome MH - Solubility MH - Temperature MH - Thermodynamics PMC - PMC8241860 DCOM- 20210816 LR - 20231101 DP - 20210629 DEP - 20210629 AB - The thermal stability of proteins can be altered when they interact with small molecules, other biomolecules or are subject to post-translation modifications. Thus monitoring the thermal stability of proteins under various cellular perturbations can provide insights into protein function, as well as potentially determine drug targets and off-targets. Thermal proteome profiling is a highly multiplexed mass-spectrommetry method for monitoring the melting behaviour of thousands of proteins in a single experiment. In essence, thermal proteome profiling assumes that proteins denature upon heating and hence become insoluble. Thus, by tracking the relative solubility of proteins at sequentially increasing temperatures, one can report on the thermal stability of a protein. Standard thermodynamics predicts a sigmoidal relationship between temperature and relative solubility and this is the basis of current robust statistical procedures. However, current methods do not model deviations from this behaviour and they do not quantify uncertainty in the melting profiles. To overcome these challenges, we propose the application of Bayesian functional data analysis tools which allow complex temperature-solubility behaviours. Our methods have improved sensitivity over the state-of-the art, identify new drug-protein associations and have less restrictive assumptions than current approaches. Our methods allows for comprehensive analysis of proteins that deviate from the predicted sigmoid behaviour and we uncover potentially biphasic phenomena with a series of published datasets.