Why Proteomics


In modern biology the suffix -omics is indicative of whole cell or whole organism analyses that involved originally the study of an organism's full complement of genes (genome-genomics) and moved on to the study of how these genes are expressed (transcriptomics) and to resolving the full complement of its protein synthesizing potential (proteome-proteomics).

Several derivative large-scale analyses of biological systems have been initiated henceforth including those that address how the whole complement of metabolites of a cell/organism change/are regulated (metabolomics). Collective terms such as systems biology are also used to describe the molecular understanding of the whole organism as a system of interacting parts. A holy grail of such studies is to produce the equivalent of "periodic tables" of cell contents, i.e. complete inventory listings of all the chemicals in a cell. In addition, such studies allow one to compare the qualitative but also quantitative inventory changes under different states of a cell, e.g. in a physiological state and in disease.

One ramification of these studies is the identification of biomarkers, molecules that can be used as descriptors of cellular states. These are invaluable in diagnosing and staging disease and evaluating its prognosis. These studies represent a paradigm shift from traditional so-called reductionist approaches that have been prevalent for the past 30 years and which allowed us to understand how cells go about carrying out individual chemistries inside them with small groups of protein complexes or protein machines (e.g. how they make and repair DNA, how they synthesize and export proteins, how they convert energy, how they communicate between them etc.). Reductionist approaches will never cease to be in use since they are the ones that provide profound understanding of biological systems all the way down to their atoms and their physics. Nevertheless, while reductionist dissection goes in depth, it is usually limited to a few of the cell's macromolecules at a time, let's say of one or a few protein machines. In contrast, -omics approaches provide fast but rather shallow information on hundreds of macromolecules at the same time. What makes marrying the two approaches inevitable is the fact that the cell in essence comprises a few hundred to a few thousand of the above mentioned machines that operate frequently in the same chamber, they exchange components between them, they are subject to modifications by the same common modifying enzymes, they are asked to do more than one tasks depending on the needs of the cell etc. Hence, the cell's proteins can be described as a dynamic "interactome" of machines. Intriguingly, this interactome appears to possess meta-properties that are more than a sum of parts. Hence both traditional reductionist protein studies as well as proteomics studies are quintessential to understanding any living cell in its normal state and in disease.

Genomic studies can be thought of as having more or less completed the requested gene inventories for hundreds of organisms. The corresponding chore is by far not completed for other -omics pursuits. This is due to the fact that genomes are relatively simple arrays of genes, stretches of DNA polymer made of only four distinct chemicals and that is used by the cell as a blueprint to make proteins. The ways in which proteins are made from the blueprint is complex and varied, with reading of segments of the DNA stretch in a non-prescribed, fixed order and with the quantity of "read" material changing depending on multi-factorial condition regimes. In addition, proteins undergo additional modifications (e.g. proteolysis, covalent binding of other chemicals such as sugars or phosphate groups on them etc) and this can affect their oligomeric state, their life-time and even their topology in the cell. Therefore, for the same number of genes a cell will have many, many more distinct protein species. Out of 30,000 genes humans may make up to a million distinct protein species. Proteomics allows the study of several (up to thousands) proteins of an organism at the same time.