Since the [Epstein-Barr virus]? was sequenced in 1984, the DNA sequence of more and more organisms is stored in electronic databases. This data is analyzed to determine genes that code for proteins, as well as regulatory sequences. A comparison of genes within a species or between different species can show similarities between protein functions, or relations between species ([phylogenetic tree]?s). With the growing amount of data, it becomes impossible to analyze DNA sequences manually. Today, computer programs are used to find similar sequences in the genome of dozens of organisms, within billions of nucleotides. The programs can compensate for mutations (exchanged, deleted or inserted bases) in the DNA sequence. A variant of this [sequence alignment]? is used in the sequencing process itself. The so-called shotgun sequencing (that was used, for example, by [Celera Genomics]? to sequence the [human genome]?) does not give a sequential list of nucleotides, but instead the sequences of thousands of small DNA fragments (each about 600 nucleotides long). The ends of these fragments overlap and, aligned in the right way, make up the complete genome. Shotgun sequencing works very fast, but the task to re-align the fragments is quite complicated. In the case of the Human Genome Project (1988-2000), it took several month on a supercomputer array to align them correctly.
Protein structure prediction is another important application of bioinformatics. The amino acid sequence of a protein, the so-called primary structure, can be easily determined from the sequence on the gene that codes for it. But, the protein can only function correctly if it is folded in a very special and individual way (if it has the correct the secondary, tertiary and quartery structure). The prediction of this folding just by looking at the amino acid sequence is quite difficult. Several methods for computer predictions of protein folding are currently (2001) under development.
There are lots of other applications of bioinformatics. [Metabolic network]?s are computer simulations of metabolic pathways that help to visualize the complex connections of cell metabolism. Morphometrics? is used to analyze pictures of embryo?s to track and to predict the fate of cell clusters during morphogenesis. [Virtual evolution]? is used to simulate evolutionary processes by computer simulations of simple life forms. Another application is the automatic search for genes and regulatory sequences within a genome. Not all of the nucleotides within a genome are genes. Within the genome of higher organisms, large parts of the DNA do not serve any obvious purpose (often called [junk DNA]?). Bioinformatics helps to bridge the gap between genome and proteome projects, for example in the use of DNA sequence for protein identification.
As a summary, it can be said that the genome projects gave us long lists of letters, and with bioinformatics, we can determine words, grammar, sentences and, finally, their meaning.
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