Proteomics

Proteins are the final products of genes that perform the function encoded by the gene. Proteins are composed of amino acids and play important roles in the cell. All enzymes (except ribozymes) are proteins and act as catalysts that affect the rate of reactions. Proteins are also regulatory molecules, and some are hormones. Transport proteins, such as hemoglobin, help transport oxygen to various organs. Antibodies that defend against foreign particles are also proteins. In the diseased state, protein function can be impaired because of changes at the genetic level or because of direct impact on a specific protein.

A proteome is the entire set of proteins produced by a cell type. Proteomes can be studied using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. The study of the function of proteomes is called proteomics. Proteomics complements genomics and is useful when scientists want to test their hypotheses that were based on genes. Even though all cells in a multicellular organism have the same set of genes, the set of proteins produced in different tissues is different and dependent on gene expression. Thus, the genome is constant, but the proteome varies and is dynamic within an organism. In addition, RNAs can be alternatively spliced (cut and pasted to create novel combinations and novel proteins), and many proteins are modified after translation. Although the genome provides a blueprint, the final architecture depends on several factors that can change the progression of events that generate the proteome.

Genomes and proteomes of patients suffering from specific diseases are being studied to understand the genetic basis of the disease. The most prominent disease being studied with proteomic approaches is cancer (Figure 10.17). Proteomic approaches are being used to improve the screening and early detection of cancer; this is achieved by identifying proteins whose expression is affected by the disease process. An individual protein is called a biomarker, whereas a set of proteins with altered expression levels is called a protein signature. For a biomarker or protein signature to be useful as a candidate for early screening and detection of a cancer, it must be secreted in body fluids such as sweat, blood, or urine, so that large-scale screenings can be performed in a noninvasive fashion. The current problem with using biomarkers for the early detection of cancer is the high rate of false-negative results. A false-negative result is a negative test result that should have been positive. In other words, many cases of cancer go undetected, which makes biomarkers unreliable. Some examples of protein biomarkers used in cancer detection are CA-125 for ovarian cancer and PSA for prostate cancer. Protein signatures may be more reliable than biomarkers to detect cancer cells. Proteomics is also being used to develop individualized treatment plans, which involves the prediction of whether or not an individual will respond to specific drugs and the side effects that the individual may have. Proteomics is also being used to predict the possibility of disease recurrence.

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Figure 10.17 This machine is preparing to do a proteomic pattern analysis to identify specific cancers so that an accurate cancer prognosis can be made. (credit: Dorie Hightower, NCI, NIH)

The National Cancer Institute has developed programs to improve the detection and treatment of cancer. The Clinical Proteomic Technologies for Cancer and the Early Detection Research Network are efforts to identify protein signatures specific to different types of cancers. The Biomedical Proteomics Program is designed to identify protein signatures and design effective therapies for cancer patients.

Genome mapping is similar to solving a big, complicated puzzle with pieces of information coming from laboratories all over the world. Genetic maps provide an outline for the location of genes within a genome, and they estimate the distance between genes and genetic markers on the basis of the recombination frequency during meiosis. Physical maps provide detailed information about the physical distance between the genes. The most detailed information is available through sequence mapping. Information from all mapping and sequencing sources is combined to study an entire genome.

Whole genome sequencing is the latest available resource to treat genetic diseases. Some doctors are using whole genome sequencing to save lives. Genomics has many industrial applications, including biofuel development, agriculture, pharmaceuticals, and pollution control.

Imagination is the only barrier to the applicability of genomics. Genomics is being applied to most fields of biology; it can be used for personalized medicine, prediction of disease risks at an individual level, the study of drug interactions before the conduction of clinical trials, and the study of microorganisms in the environment as opposed to the laboratory. It is also being applied to the generation of new biofuels, genealogical assessment using mitochondria, advances in forensic science, and improvements in agriculture.

Proteomics is the study of the entire set of proteins expressed by a given type of cell under certain environmental conditions. In a multicellular organism, different cell types will have different proteomes, and these will vary with changes in the environment. Unlike a genome, a proteome is dynamic and under constant flux, which makes it more complicated and more useful than the knowledge of genomes alone.

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