Biomarkers have a central role in the drug discovery and development processes. Biomarker / biomarkers can be sought after to identify the proteins and pathways involved in disease status leading to target discovery or diagnostics purposes. Alternatively biomarkers can be discovered to allow early measurements of the intervention’s safety and efficacy.
Our expertise is in proteomics
Proteins are the machinery of the cell, responsible for performing the functions essential for cells to operate, survive, grow and divide. Functional proteins control which genes are activated and when. Proteins are also e.g. responsible for signals within and between cells driving biological and metabolic processes. In most cases, changes at protein level determine the differences between sickness and health and once discovered, may be used to monitor the progression or make prognosis of disease. Further all drugs on the market and being developed act by trying to alter the protein malfunction. Typically the first step in drug discovery project is the identification and validation of the protein target(s) or markers associated with a disease.
This is why proteins are excellent biomarkers for various purposes (efficacy, prognosis, patient stratification, toxicity detection etc.). We provide services for discovery and verification of proteomics biomarkers for both non‐clinical and clinical purposes.
Protein biomarker platform
Our biomarker discovery and validation platform utilizes high-end proteomics combined with bioinformatics and computational systems biology capabilities. This service covers aspects including designing of the discovery process from statistical point‐of‐view, sample preprocessing and proteomics analysis followed by bioinformatics data analysis. All of the stages of the biomarker discovery platform are tailored per the customers needs, progress and own capabilities.
Our typical protein biomarker discovery project begins with untargeted protein identification and quantification (shotgun or bottom-up proteomics). This is done with nanoLC-MS/MS platform, capable of identifying and simultaneously quantifying few thousands of proteins form each sample. The quantification can be enhanced with iTRAQ etc. labeling, which is recommended in most cases. This protein discovery stage is in most cases run for few 10s of samples, for which the endpoint (like good response to the drug) is known or e.g. samples which have been treated the same way (like comparison between different drugs/compounds). In addition to protein levels, the search can also be focused to e.g. changes in protein phosphorylations or other PTMs.
The sample material can be practically any biological material, like blood, plasma, serum, CNS fluid, urine, solid tissues, and even formalin fixed paraffin embedded tissue slides.
With bioinformatics and systems biology methods, we develop a model aiming to explain the observation by the detected differences in protein levels.
In the next step, the found candidate biomarkers targetedly quantified in larger number of samples. We switch form shotgun proteomics to targeted proteomics approches. We us a modern technology called MRM nanoLC-MS/MS, which allows one to focus on list (typically few tens) of proteins, whihch are quantitated form the samples with MRM. This method has very significant advantage over e.g. ELISAs and other immunodetection methods, since it does need any antibodies for detection. Rather the candidate proteins are directly chosen (from biomarker discovery or from any other list) and quantified fromt the samples – there is no need to test different antibodies and optimize them for the ELISAs/immunodetections for the few tens of proteins! IN this stage we develop the MRM methods and start quantifying the samples by automatized MRM runs.
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