Proteomics

Proteomics is transforming our understanding of biological systems and disease mechanisms. With the ability to peer into thousands of proteins simultaneously, mass spectrometry-based proteomics empowers scientists to reveal previously unknown protein interactions, pathways, drug targets, and predictive biomarkers. Evotec’s proteomics  platform is the best-in-class, and among the largest  mass spectrometry-based proteomics facilities worldwide. With over 15 years of success in proteomics driven drug discovery , Evotec provides highly optimized and robust experimental strategies tailored to different projects’ needs. 

High sensitivity and accuracy are achieved by combining high-end mass spectrometry instrumentation with appropriate sample preparation and data acquisition methods. Importantly, our mass-spectrometry based proteomics platform can detect and quantify different protein isoforms as well as their post-translational modifications. The ability to profile different aspects of the proteome in an unbiased way, and at an industrial scale, is critical in accelerating drug discovery. 

Our high-throughput proteomics platform ScreenPep^TM enables the analysis of thousands of samples at an unprecedented speed and depth, detecting beyond 10,000 proteins from cells or tissues. One of the key advantages of ScreenPep is being able to benefit from high-throughput without compromising coverage and precision. 

This is achieved by high-end mass spectrometry instrumentation with automated sample preparation. All stages, starting from cell culture, sample  preparation  to data acquisition using LC-MS/MS and ending with data processing and analysis have been highly optimized in recent years. ScreenPep is now a fully automated and quality-controlled workflow from the sample to the final result. 

The unbiased proteomics analysis can be complemented by global analysis of different post-translational modifications. Slightly adapted workflows enable us to quantify more than 20,000 phosphorylation sites, more than 40,000 ubiquitination sites, or more than 1,000 acetylation or methylation sites.  

The ScreenPep platform supports target discovery on the functional protein or protein modification level. It enables unbiased mode of action studies, the identification of specific pharmacodynamic read-outs and lead compound prioritization according to cellular activity profiles. In particular, the platform allows to screen libraries of 1000s of compounds for the impact on the protein expression (such as targeted protein degraders) or protein modification (such as kinase inhibitors).  

Our offering comprises: 

• Leading expertise in quantitative mass spectrometry, utilizing metabolic or chemical isotope labelling or label-free quantification 
• Bio-orthogonal chemical reporter strategies for specific profiling of newly synthesized proteins or various glycoproteins, including N- and O-linked glycoproteins, O-GlcNAc modified proteins, and sialic acid modified proteins 
• Experience and infrastructure to analyze the enormous amounts of data generated in large-scale proteomics projects 
• Advanced statistics and bioinformatics for system-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

Evotec offers a flexible and versatile platform 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. 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 individualized therapies but also broadens the understanding about molecular mechanisms involved in disease progression.  For further validation of the identified single proteins or protein signature as biomarkers, Evotec can develop immune-based assays or targeted mass-spectrometry assays using parallel reaction monitoring (PRM). Both methods allow the absolute quantification of the protein biomarkers in large cohorts of samples in Research-Use-Only (RUO) and Good-Clinical-Practice (GCP) environments.

As part of a strategic alliance with Seer Inc., Evotec is the only 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 with you with regard to study size, selection of treatment paradigm, collection of patient metadata and provide you with guidelines, e.g. for minimizing 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 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 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. 
• Industrialized, 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
• Leading expertise in statistics, machine learning, and bioinformatics for the identification and validation of univariate and multivariate markers in the context of relevant disease models or patient data

High Sensitivity proteomics, also often referred as Single Cell proteomics, is a nascent field branching from mainstream proteomics. With the advent of the latest high sensitivity mass spectrometers, combined with high sensitivity chromatographic systems, enables unprecedented depth of coverage for low input sample material. At Evotec, we have developed lossless sample preparation for low input material and further optimized data acquisition strategies to extent maximum proteome depth possible from low sample amounts. From as low as 200 pg of sample amount up to 4,000 proteins could be quantified using our highly streamlined and optimized workflow. This technology is readily applied for single cell proteomics as well as other low input materials like tissue specific exosomes, as little as 1 µl of mouse CSF to name a few.  

The sensitivity of our technology can be readily applied for spatial proteomics. One of the most common available biobank sample formats namely FFPE tissue blocks, can be used for spatial proteomics. Sections in the range of 5 to 20 µm thick could be mounted on PEN membrane slides and stained with H/E or IHC reagents for image acquisition. These images are analyzed using classical or machine learning approaches to identify regions or shapes of interest to quantify region specific proteomes. To perform such studies, Evotec is equipped with a cutting-edge laser capture microdissection device that can collect samples also in 96 and 384-well plate formats to enable high-throughput spatial proteomics studies.  

Adjacent sections obtained from tissue blocks could be used for spatial transcriptomics and spatial proteomics. The data can be analyzed in Evotec’s unique PanHunter platform, enabling spatial multi-omics in a streamlined fashion.

Evotec has strong expertise in the analysis of MHC class I and II 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 tumors and infected cells. 

Our offering comprises:

• High end peptidomics workflow enabling the enrichment and the detection of MHC class I and II 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