Proteomics and metabolomics

Evotec offers unique proteomics and metabolomics services to address key issues in drug and biomarker discovery. We continuously advance our capabilities in mass spectrometry-based proteomics and metabolomics to ensure unrivalled comprehensiveness and data quality when analysing cells, animal models and patient samples.

Our offering comprises: 

• Global protein expression and modification analysis enabling unbiased drug mode of action and target engagement studies
• Proteome-wide discovery of biomarker candidates  in cells, tissues and body fluids, complemented by targeted mass spectrometry platforms for validation of investigational protein biomarkers
• Evotec Cellular Target Profiling™ and drug photoaffinity labelling for target deconvolution of bioactive compounds

• Chemical proteomics applications for unbiased and quantitative drug selectivity analysis in the context of native proteomes or sub-proteomes
• Advanced MHC peptidomics profiling enabling the identification of neo-antigens presented by tumours and infected cells
• Targeted metabolomics for in vitro and in vivo quantification of metabolites in cells, tissues, body fluids or awake animals
• In-depth statistical and bioinformatics analysis

Global Proteome Expression and Modification Analysis

Evotec offers advanced technologies for unbiased protein expression and modification analysis of almost any type of biological samples including cells, tissues, body fluids, insects, fungi, and plants. Evotec’s global proteomics platforms support target discovery on the functional protein level.

Likewise, they enable unbiased mode of action studies, the identification of specific pharmacodynamic read-outs and lead compound prioritisation according to cellular activity profiles.

Our offering comprises:

• High-end proteomics workflows monitor 10,000 distinct proteins, more than 20,000 phosphorylation sites, more than 8,000 ubiquitination sites, or more than 1,000 acetylation or methylation sites
• Leading expertise in quantitative mass spectrometry utilising metabolic or chemical isotope labelling or label-free quantification

• Bio-orthogonal chemical reporter strategies for specific profiling of newly synthesised proteins or various glycoproteins, including N- and O-linked glycoproteins, O-GlcNAc modified proteins, and sialic acid modified proteins
• Specialised enrichment strategies enabling the analysis of post-translational modifications on histones (HistoneScout)

• Experience and infrastructure to analyse the enormous amounts of data generated in large-scale proteomics projects
• Advanced statistics and bioinformatics for systems-wide data analysis
• In-depth data interpretation to extract relevant drug target and mode of action information from proteomics experiments
• Extensive track record to deliver high quality results within agreed timelines

Biomarker discovery and validation

Evotec offers a unique platform of innovative proteomics and metabolomics technologies to address key issues in translational biomarker discovery and validation in various therapeutic areas. Both the expertise and the data processing infrastructure are in place for accurate quantification across many different samples, enabling integrated, large-scale projects to discover and validate diagnostic, pharmacodynamic or predictive biomarkers.

Our offering comprises:

• Tailor-made workflows enabling either proteome profiling for quantitative analysis across thousands of samples, or deep proteome profiling for detection of more than 10,000 proteins from cells or tissues 
• In-depth, quantitative protein biomarker discovery in body fluid samples such as plasma and CSF
• Industrialised, QMS supported process enables analysis of thousands of samples with constant high quality

• Full capabilities to develop targeted mass spectrometry assays based on parallel reaction monitoring (PRM) for high-throughput verification and validation of candidate biomarkers
• In vitro and in vivo targeted metabolomics enabling various pre-clinical and clinical translational biomarker applications
• Leading expertise in statistics and bioinformatics for the identification and validation of univariate and multivariate markers in the context of relevant disease models or patient data

Clinical Proteomics

Evotec offers a flexible and versatile platform for the support of clinical studies from medium sized and large cohorts to support human patient studies as well as animal health activities. Using high-throughput proteomics workflows we analyze body fluids such as plasma, serum, cerebrospinal fluid, urine but also fresh-frozen or FFPE tissue or other suited clinical samples. 

This unbiased approach allows to identify proteins that can serve as novel diagnostic or predictive biomarkers to allow patient stratification for individualised therapies but also broadens the understanding about molecular mechanisms involved in disease progression.

As part of a strategic alliance with Seer Inc., Evotec is the first Center of Excellence in Europe to offer access to the fully automated nanoparticle based Proteograph^TM platform. This enables us to perform plasma and serum proteomics at an unprecedented depth of up to 5,000 identified and quantified proteins.

Our offering comprises

• Support with study design and sample collection to generate optimal input material for proteomics or multi-omics studies. Our bioinformatics experts and specialists for different therapeutic areas will consult you with regard to study size, selection of treatment paradigm, collection of patient metadata and provide you with guidelines, e.g. for minimising technical variability between samples for multi-centric studies. Evotec’s quality control comprises standardized recording of sample properties (e.g. automated analysis of hemoglobin levels) upon receipt and takes into account possible sources of contamination that might confound data interpretation. 

• Depending on the scope of your study we will offer various techniques for sample preparation, e.g. chromatographic depletion, antibody-based depletion, automated sample preparation using minimal input material (down to 1-5 µl for plasma or serum samples). In addition, the Proteograph^TM platform offers you a unique window to unbiased detection of low abundant proteins, such as cytokines from body fluids and other challenging samples.

• Parallel proteomics analysis of multiple sample types from a single donor, e.g. tissue biopsies, plasma, cerebrospinal fluid, urine, PBMC to generate comprehensive data sets that allow to understand disease progression or decipher individual responses to a treatment scheme.
• Integrated multi-omics studies combining proteomics with transcriptomics, metabolomics and complementary omics techniques. We support you not only to generate extraordinary data sets but also offer a unique service to fully explore your multi-omics data using Evotec’s proprietary EVOpanHunter platform.

Chemical proteomics and target deconvolution

Evotec scientists have pioneered chemical proteomics applications to support target deconvolution of bioactive compounds emerging from phenotypic screens. Cellular target identification is the crucial step to enable further drug optimisation and development.
Evotec Cellular Target Profiling™ is a powerful technology to identify specific cellular compound targets in lysates from any cell type or tissue.  Evotec’s chemical proteomics offering further comprises photoaffinity labelling for covalent target capture in live cells.

Our offering comprises:

• Evotec’s chemical proteomics approaches use high-end quantitative mass spectrometry to reveal and verify specific cellular targets of a drug
• Evotec Cellular Target Profiling™ determines target-specific dissociation constants for the compound studied, ranking targets according to their likely physiological relevance
• Drug photoaffinity labelling supports binding site identification in protein targets and complexes

• Unbiased target ID by proteome-wide profiling of  native, endogenously expressed, post-translationally modified proteins in the presence of cellular co-factors and native complex partners
• Complementary chemical proteomics approaches can be performed in an integrated fashion
• Extensive, non-target class restricted track record in successful profiling of diverse small molecule compounds

Chemical Proteomics - Drug Selectivity and Activity Profiling

Evotec has established a chemical proteomics platform which employs high-end quantitative mass spectrometry for compound selectivity analysis in the context of native proteomes and sub-proteomes. Selectivity data about cellular on- and off-target liabilities is particularly useful for informed decisions at various stages of drug development, for example in the lead optimisation phase or in the pre-clinical candidate selection process.

Our offering comprises:

• Evotec Cellular Target Profiling™ for unbiased, proteome-wide selectivity profiling to identify and quantify compound interactions with cellular on- and off-targets

• KinAffinity^® as Evotec’s hit-to-lead compatible approach for rapid target profiling of kinase inhibitors in cell and tissue samples. Unlike traditional biochemical kinase panel screening, the inhibitor’s target affinities are determined simultaneously for a large number of native kinases within their physiological cellular environment
• Activity-based protein profiling (ABPP) of a wide range of enzyme classes including serine hydrolases, metalloproteases, oxidoreductases, histone deacetylases, and glutathione S-transferases. ABPP visualises only the active forms of particular enzymes using reactive chemical probes directed to the active site of a particular target protein family

MHC Peptidomics Profiling

Evotec has strong expertise in the analysis of MHC class I peptidomes of cells, animal tissues, and patient derived samples. The workflow enables the discrimination of biological samples based on presented peptides, the generation of target hypotheses, and the discovery of neo-antigens presented by tumours and infected cells.

Our offering comprises:

• High-end peptidomics workflow enabling the enrichment and the detection of MHC class I presented peptides

• Parallel deep sequencing of samples to generate sample specific peptide sequence databases 
• Advanced bioinformatics workflow for the identification of neo-antigens and the discrimination of biological samples
• Expertise in validation of immunogenicity of identified neo-antigens combined with extensive expertise in immune-oncology and infectious diseases at Evotec

Metabolomics

Evotec has established expertise and state-of-the-art methodologies in targeted metabolomics for the functional analysis of metabolic networks with applications in health, biotechnology and microbiology.
Evotec offers unique in vitro, ex vivo and in vivo targeted metabolomics services to address key issues in biomarker discovery and/or validation in various therapeutic areas including cancer, metabolic syndrome, diabetes, CNS and cardiovascular diseases.

Applications of metabolomics include:

• Pre-clinical biomarker identification
• Disease mechanism and validation of animal models for disease
• Discovery of biomarkers for patient stratification as well as clinical safety and efficacy assessment

Our targeted metabolomics approach focuses on the analysis of specific group of metabolites related to certain metabolic pathways or a class of compounds including lipids (phospholipids, lysophospholipids, sphingolipids, and neutral lipids), endocannabinoids, eicosanoids, corticosteroids, neurosteroids, oxysterols, nucleotides free fatty acids, and nicotinamide metabolome.
Due to its sensitivity and specificity, our approach allows absolute quantitation of metabolites using selected reaction monitoring (SRM), with detection limit of ng/mL, in sample matrices (e.g. biofluids, cells, organs) and also in vivo on awake or anesthetised animals using microdialysis coupled with XLC-MS/MS.

Statistics and bioinformatics analysis

Evotec’s bioinformatics group developed strong expertise in the analysis of proteomics, transcriptomics, and other OMICs data supporting mode of action studies, the discovery of biomarker candidates, and the identification of novel targets.

Our offering comprises:

• Extensive quality control of experimental data using clustering and principal component analysis, outlier detection methods, and advanced normalisation methods

• Biostatistical analysis for the identification of regulated proteins, genes, or PTMs by applying statistical tests such as ANOVA, LIMMA, but also the in-house developed and peer-reviewed MeanRank test
• Functional analysis of affected pathways, protein classes, and protein complexes. This includes the identification of regulated sub-modules of protein-protein-interaction networks by means of the in-house developed, and published SubExtractor algorithm

• Data analysis pipeline for the identification of multivariate biomarker signatures using advanced machine learning methods
• Integrated software infrastructure supporting the processing of mass spectrometry raw data, quality control, statistical and bioinformatics analysis, data visualisation, and data storage