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Chemical Proteomics and Proteogenomics

National facility

Chemical Proteomics & Proteogenomics is a national facility that offers state-of-the art mass spectrometry (MS)-based proteomics support to the Swedish research community. The facility also offers expert support in experimental planning, MS analysis and data analysis related to proteogenomics and chemical proteomics. This is a joint facility composed by two sites, both in Stockholm: one for chemical proteomics at the Biomedicum building of Karolinska Institutet and one for proteogenomics at the SciLifeLab site.  The chemical proteomics and proteogenomics facility is also a node in Swedish National Mass Spectrometry Facility BioMS, more information see bioms.se.

 

Chemical Proteomics in brief

Chemical proteomics uses orthogonal MS-based and proteome-wide approaches to identify key proteins relevant the phenotype produced by a treatment. Traditionally, chemical proteomics includes affinity capture approaches using compounds as bait to study interacting proteins. Today systems (usually constituted of cells in culture or lysates) can be perturbed with an active compound/small molecule with no need of modification for chemical probe engineering; the perturbed systems are then analyzed by proteome-wide quantitative approaches for deconvolution of targets, determination of the mechanism of action and of the off-target landscape. Orthogonal chemical proteomics approaches can be based on: early proteome signatures of solubility/stability alterations as in thermal profiling approaches (PISA and TPP); treatment-specific signatures of expression/degradation proteome regulation; changes in proteome redox balance in treated cell cultures. New high throughput approaches dramatically reduce costs and time, allow higher number of biological replicates and increase data robustness and reproducibility. MS based protein structure analysis via HDX-MS (hydrogen-deuterium exchange MS) can elucidate the binding site of interaction once the target has been determined even in cases of failure of other protein structure approaches.

 

Proteogenomics in brief

Proteogenomics is a new exciting field in biological mass spectrometry that combines proteomics information with sample specific genomic and transcriptomics information. Applications in proteogenomics include discovery of novel protein coding regions to improve genome annotation; detection of variant and mutated proteins based on DNA and/or RNA sequence data; discovery of cancer neoantigens and evaluation of the impact of genomic changes (e.g. copy number alterations, SNPs, mutations, hyper methylation) on the proteome. We can also provide in-depth proteomics data for comprehensive systems biology studies.