E-learning in analysis of genomic and proteomic data 1. Introduction 1.1 Recent challenges in modern genomic and proteomic analysis 1.1.1. Questions arising from current medical and biological research

1.1.1.  Questions arising from current medical and biological research

The genes are expressed and proteins created according to the individual needs of a cell or whole organism. This of course means that not all the genes are active (producing the proteins or functional RNAs) at the same time. The activity of a gene varies also in its intensity. Some genes are active more, some less, some not at all. It is the regulation of the activity of specific genes and the regulation of the structure of their products that helps the cell or an organism to response on different stimuli of the environment, to adapt and survive.

The different gene activity is a reason for the differences between the cells of different tissues in an organism. If not so, how would it be possible that neuron cells are completely different both in their shape and function in comparison to skin cells, when they contain in their nucleuses exactly the same DNA?
              Thousands of genes are being expressed and translated to proteins in each moment of the cell existence and there are thousands of very complex pathways regulating these processes. The deregulation of any of the processes can cause serious problems not only to the cell but to the whole organism. For this purpose, there is a number of control mechanisms, such as mechanisms controlling the repair of mismatched nucleotide bases, a process that often occurs during the DNA replication. If for any reason this repairing process fails and the wrong DNA is produced, other proteins direct the cell to a programmed cell death called apoptosis. The deregulation of this apoptosis process is one of the main mechanisms causing the development of cancer.
 

The deregulation of any complex process can be caused by different mechanisms:

• Changes in gene expression (inappropriate deactivation or activation of a gene) resolving in too low or too high abundance of a protein in a pathway caused either by gene transcription regulation mechanism distortion or gene aberrations.
• A single nucleotide mutation in a gene resolving in a non-functional protein or a protein with changed function.
• Changes in post-translational modification of proteins causing the dysfunctionality or unexpected different function of a protein.

Each of these deregulations can resolve in development of a disease and can be its only cause. This is true particularly in oncology as the tumor cells are well known by their genomic instability that gives them an advantage over normal cells to survive in all conditions, uncontrollably proliferate and invade into other tissues than the one of their origin.
With this knowledge it is straightforward to understand the importance of the knowledge of the gene structure, the gene expression control mechanisms and the underlying biological processes of a cell and organism. Decoding the complete sequence of a genome of any organism is a first step in this understanding and always brings new challenges in biomedical research. The knowledge of gene sequence helps to understand the regulation of gene expression, function of its product (usually protein) and its importance and involvment in biological pathways. In medicine, the decoding of human genome in Human Genome Project brought new hope of possibility to correlate genes and their mutations with different diseases. This would allow for finding the optimal prevention and diagnostics of diseases and the best targeted therapy with maximal effectivity and minumum of side effects. In biology, by comparing the genomes of different species, we already search for the evolutional connections and are able to construct phylogenetic trees. The study of gene expression of bacteria or cell lines under different conditions can help to reveal the mechanisms of adaptation and survival.
 

The technology available for identification of gene structure, gene expression or protein structure depends on the type of specimens available for study (bacterias, white blood cells and their DNA content, tumor tissue and its DNA/mRNA content, or blood serum or plasma and its proteomic and metabolomic content) and the type of molecules we want to study.
We can search for the differences

• on the genome level (mutations in genes, changes in copy numbers of genes or whole chromosomes) – studying the DNA molecules
• the changes in gene expression level - studying the RNA molecules
• or changes in the abundance or the structure of proteins between different samples – studying the proteins

The next chapter describes some of the technologies with focus on the the modern high-density methods of genome and proteome analysis.