Proteomics: applications in transfusion medicine.

Abstract

Since the completion of the mapping of the human genome1,2, which allowed the identification of over 30,000 genes, continuous efforts have been made to associate the data acquired with DNA functions. New tools for analysing these data have been developed and new disciplines of study have been generated to explore the whole range of the potential applications of human genome-related information; the names of all these new fields of study end in omics. Genomics is the comprehensive analysis of DNA structure and function, whereas transcriptomics is the study of the mRNA pool found within a cell and describes gene expression3, proteomics instead studies the location, structure and function of proteins expressed in a biological system4. The genome is the total chromosome (hereditary) content of a biological system, while the proteome is all the proteins that the genome produces through biological transcription and translation5. The term “proteome” (PROTEins expressed by a genOME) was coined by Wilkins and colleagues in 19966. Initially the word proteomics referred to the techniques used to analyse a large number of proteins at the same time, but, at present, this word covers any approach that yields information on the abundance, properties, interactions, activities, or structures of proteins in a sample7. The name “protein”, derived from the Greek term proteios, meaning “the first rank”, was used for the first time by Berzelius in 1838 to emphasise the importance of these molecules8. The number of proteins produced by the 30,000–40,000 genes of the human genome is estimated to be three or four orders of magnitude higher9. The reasons for this numerical superiority and complexity are4,10: i) differential splicing of mRNA gene transcripts, which allows a single gene to produce multiple protein products; ii) the capability many proteins have of associating with other proteins to form complexes; iii) post-translational modifications, which are additional changes that proteins initially translated within a cell may undergo. These are covalent modifications that regulate protein functions, determining their activity state, cellular location and dynamic interactions with other proteins; the most important and best-studied post-translational modifications are phosphorylation and glycosylation, but many others are common (acetylation, methylation, lipid attachment, sulphation of tyrosine, ubiquitination and disulphide bond formation) among over 300 different known types. The genome, compared to the proteome, is stable4,5; the proteome, on the other hand, is dynamic and changes based on the type and functional state of a cell. The number of proteomes that can be defined within a biological system therefore increases as the complexity of the latter becomes greater7; indeed the number of proteomes within a cell is much lower than the number within a tissue and really much lower than the one within an organism. This makes proteomics a challenging field, largely due to the sheer size of the proteome and the volume of data that can be generated by it11. Transfusion medicine is a clinical discipline characterised by one of the most advanced quality management systems, which is structured so as to assure the production of blood components and raw materials, for biopharmaceutical fractionation, which are safe, efficient and effective12. In Italy, the collection and production procedures performed at blood banks are closely regulated by State laws and/or directives issued by government agencies. At present, proteomics seems to be the most promising tool for global quality assessment of the production process of blood components and blood derivatives. The potential role of proteomics in transfusion medicine has been addressed in several articles, since 20044,7,12–15. The objective of this review is to provide a brief overview of contemporary proteomics technologies and published studies on their applications in transfusion medicine, which are mainly the characterisation of blood product proteomes and their modifications caused by production or storage processes.