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Background

Proteome

A proteome is the entire complement of proteins, including modifications made to a particular set of proteins, produced by an organism or a cellular system. This will vary with time and distinct requirements such as growth conditions and stresses, and thus is highly dynamic and spatial. Proteomics is the study of the proteome.

Proteomics

The term "proteomics" refers to a large-scale comprehensive study of a specific proteome resulting from its genome, including abundances of proteins, their variations and modifications, and interacting partners and networks in order to understand cellular processes involved. Similarly, "Cancer proteomics" refers to comprehensive analyses of proteins and their derivatives translated from a specific cancer genome using a human biospecimen or a preclinical model (e.g., cultured cell or animal model).

Currently, there are two main types of proteomic studies: discovery proteomics and targeted proteomics. The term "discovery proteomics" is in reference to "untargeted" identification and quantification of a maximal number of proteins in a biological or clinical sample. The term “targeted proteomics” refers to quantitative measurements on a defined subset of total proteins in a biological or clinical sample, often following the completion of discovery proteomics studies to confirm interesting targets selected. Commonly used proteomic technologies and platforms are different types of mass spectrometry and protein microarrays depending on the needs, throughput and sample input requirement of an analysis, with further development on nanotechnologies and automation in the pipeline in order to improve the detection of low abundance proteins, increase throughput, and selectively reach a target protein in vivo. Bioinformatic tools and methods are also a crucial part of proteomic studies.

Despite recent technological advances in proteomics, comprehensively characterizing an entire proteome still poses a challenge inherent in proteomics. This lies in a proteome's increased degree of complexity compared to its genome and argues for the need of continuous development of technology/platform. For example:

  • One gene can encode more than one protein. The human genome contains about 21,000 protein-encoding genes, but the total number of proteins in human cells is estimated to be between 250,000 to one million.
  • Proteins are dynamic and spatial. Proteins are continually undergoing changes, e.g., binding to the cell membrane, partnering with other proteins to form complexes, or undergoing synthesis and degradation. The genome, on the other hand, is relatively static.
  • Proteins are co- and post-translationally modified. The types of proteins measured can vary considerably from person to person under different environmental conditions, or even within the same person at different ages or health status. Additionally, certain modifications such as phosphorylation are highly dynamic while regulating the function of their respective proteins.
  • Proteins exist in a wide range of concentrations in the body. For instance, if working with blood, the concentration of albumin is more than a billion times greater than that of interleukin-6, making it extremely difficult to detect low abundance proteins in a complex biological matrix. Scientists believe that the most important proteins such as p53 for cancer may be those found in the lowest concentrations.

Proteogenomics

Proteogenomics, or the integration of proteomics with genomics and transcriptomics, is an emerging approach that promises to advance basic, translational and clinical research. By combining genomic and proteomic information, leading scientists are gaining new insights due to a more complete and unified understanding of complex biological processes.

The Human Genome Project taught us a tremendous amount of cancer biology, and now, the next logical layer of the onionskin that needs to be peeled off is its proteome. The reason is that while DNA (genome) serves as the blueprint for proteins (proteome), it is those proteins that are the workhorses of every living cell in the human body. While genomics has traditionally dominated clinical omics-based research, recently through efforts by CPTAC, it is becoming increasingly clear that in order to understand the genome, one needs to have a firm understanding of the proteome, including its post-translational modifications (PTMs). And the reason is two-fold: first - proteins are the targets of most anti-cancer drugs and therapies, and second - studies now show that potentially meaningful changes at the proteomic level are not always present at the genomic level. Looking globally, the value of proteogenomics in oncology for defining the molecular signature of human tumors, and translation to other areas of biomedicine and life sciences is anticipated.