Since the Epstein-Barr virus was sequenced in 1984, the DNA sequence of more and more organisms is stored in electronic databases. These data are 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 (the use of molecular systematics to construct phylogenetic trees). 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. These programs can compensate for mutations (exchanged, deleted or inserted bases) in the DNA sequence, in order to identify sequences that are related, but not identical. 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 yields sequence data quickly, but the task to re-align the fragments can be quite complicated for larger genomes. In the case of the Human Genome Project, it took several months on a supercomputer array to align them correctly. Shotgun sequencing is generally preferred for smaller genomes, such as bacteria, and often used at least partially on organisms with much larger genomes.
Another aspect of bioinformatics in sequence analysis 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. This so-called junk DNA may, however, contain unrecognized functional elements. Bioinformatics helps to bridge the gap between genome and proteome projects, for example in the use of DNA sequence for protein identification.
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 secondary, tertiary and quaternary 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 (as of 2004) under development.
One of the key principles in bioinformatics is homology. In the genomic branch of bioinformatics, homology is used to predict the function of a gene. If gene A is homologous to gene B of which the function is known, it is likely to have a similar function. In the structural branch of bioinformatics homology is used to determine which parts of the protein are important in structure formation and interaction with other proteins. In a technique called homology modelling, this information is used to predict the structure of a protein once the structure of a homologous protein is known. This currently remains the only way to predict protein structures reliably.
One case example of this is the similar protein homology between hemoglobin in humans and the hemoglobin in legumes (leghemoglobin). Both serve the same purpose of transporting oxygen in both organisms. Though both of these proteins have completely different amino acid sequences, their protein structures are virtually identical, which reflects their near identical purposes.
Systems biology involves the use of computer simulations of cellular subsystems (such as the networks of metabolites and enzymes which comprise metabolism, signal transduction pathways and gene regulatory networks) to both analyze and visualize the complex connections of these cellular processes. Artificial life or virtual evolution attempts to understand evolutionary processes via the computer simulation of simple (artificial) life forms.
The Ensembl Project Ensembl is a joint project between EMBL-EBI and the Sanger Centre to develop a software system which produces and maintains automatic annotation on eukaryotic genomes. http://www.ensembl.org/
The Open Lab A community focused on the freedom of information as it pertains to the biosciences. http://bioinformatics.org/
The International Society for Computational Biology The International Society for Computational Biology is dedicated to advancing the scientific understanding of living systems through computation; the emphasis is on the role of computing and informatics in advancing molecular biology. http://www.iscb.org
The Bioinformatics Resource The site of CCP11 (Collaborative Computational Project 11) the goal of which is to "to foster the broad bioinformatics community and the UK research community in particular". Comprehensive list of links, including information on courses, conferences and workshops that they run. http://www.hgmp.mrc.ac.uk/CCP11/
European Molecular Biology Network EMBnet is the only organisation world-wide bringing bioinformatics professionals to work together to serve the expanding fields of genetics and molecular biology. http://www.embnet.org/
Bioinformatics and Biological Computing Comprehensive bioinformatics site, with access to multiple database searching and sequence analysis tools - from the Weizmann Institute of Science. http://bioinfo.weizmann.ac.il/
Biodatabase Mining Whitepaper on database mining in the Human Genome Initiative. http://biodatabases.com/whitepaper.html
Society for Bioinformatics in the Nordic countries SocBiN is a non-profit organisation for people working with and interested in bioinformatics. One task of the society is to arrange annual conferences on Bioinformatics, of which the first took place April 1999 in Lund. http://www.socbin.org/
DNA Structural Atlas Easy-to-use summary of genomic information currently available for all organisms-from the Technical Univ. of Denmark. http://www.cbs.dtu.dk/services/GenomeAtlas/
Iranian Bioinformatics Research Center Research on Bioinformatics topics include: Genomics, Drug discovery, intelligent agent applications, sequencing, pattern matching, complex algorithms, distributed Databases, pharmaceogenomics, ... http://www.Bio-IT.org
The Swiss Institute of Bioinformatics Homepage (SIB) SIB operates the ExPASy proteomics server and the Swiss node of EMBnet. Teaching activities include a series of post-graduate courses given at the Universities of Geneva and Lausanne, as well as at the EPFL, and a Masters Degree in bioinformatics. Major research areas include the development of integrated databases and software resources in the field of proteomics. http://www.isb-sib.ch/
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