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Precision Medicine


Figure 2   


 


C C 


 antibody costs too high for clinical application


K Ubq


Ubq Ubq


C S,T,Y SNO


SOH SSG SSH





Analysis requires a high amount of starting material, thus is mostly applied on cell cultures


P


 





• Studies typically focus either on glycan structure or site occupation as combined analysis challenging.


 for clinical application


K Acetyl 


 detection antibody costs too high for clinical application


 • Applied in analysis of blood, blood cells and dental pulp


S,T X=P N Acetyl


sequences encoded within the genome, in addition to various isoforms and post-translationally mod- ified variants19. Proteins are the functional molecules in the cell and as such represent actual physiological conditions. Consequently, their use as diagnostic biomarkers could be advantageous in detecting and monitoring pathological condi- tions by giving rise to earlier signals of disease or more accurate therapeutic monitoring. A myriad of protein biomarkers are already in use in clinical diagnostics, such as PSA in the detection of prostate cancer, HER2 in the detection of breast cancer20,21 and PD-L1 in the selection of respon- sive patients to immunotherapy for lung cancer22. However, these markers were identified and vali- dated prior to the omics via traditional molecular assays and their detection and analysis rely on lower throughput techniques such as enzyme- linked immunoassays (ELISAs) and other immunoassays21. For large scale proteomic measurements of pro-


teins and peptides mass spectrometry (MS) is the current favoured method, yet at present this tech- nique is more suited to protein biomarker


36


research than clinical assay. The range of limita- tions of this technology include technical com- plexity of the methods, low throughput, high cost of assay, lack of thorough analytical and clinical validation of both the methods and the proteomic biomarkers identified using this technique and, finally, problems associated with the sensitivity of the testing for specific rare proteins in protein- rich clinical samples, such as plasma, serum, fae- ces or saliva23. Thus, despite offering potential for earlier and more accurate detection of disease and location of tumours in the body, large-scale screens for proteomic biomarkers are not current- ly at the same stage of development as their genomic counterparts. Nonetheless, some companies have continued to


pursue and refine this approach, typically coupled with liquid chromatography (LC-MS), for disease biomarker identification and analysis. In 2013, Integrated Diagnostics (Indi) brought to market a blood-based diagnostic assay, Xpresys Lung, that functioned on an MS platform. This assay deter- mined the probability of lung nodules 8-30mm in size, that were identified via CT, being benign. Of


Drug Discovery World Winter 2019/20


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