THE CHEMOKINE INFORMATION SOURCE - IDENTIFICATION AND CHARACTERIZATION OF NOVEL CHEMOKINES USING THE WORLDWIDEWEB AND EXPRESSED SEQUENCE TAG DATABASES

The chemokine superfamily is a large group of more than 30 small prote ins, Many of these were originally identified because of their role in the selective recruitment and activation of leukocytes during inflamm ation, More recently, some of the chemokine receptors and Ligands have been implicated in the mechanism of viral infection for primate lenti viruses such as HIV-1, From the original identification of interleukin -8 (IL-8; the most studied member of the superfamily), the number of n ew family members has mushroomed over the last few years, Two events h ave dramatically altered the speed at which sequence information conce rning novel chemokines has become available to the scientific communit y, First, many groups have been obtaining large amounts of sequence in formation from cDNA libraries by sequencing the clones at random, gene rating expressed sequence tags (ESTs), Although these ESTs are relativ ely short, typically less than 500 bases, this amount of sequence is u sually sufficient to obtain the entire open reading frame for chemokin es, Second, there has been a rapid growth in the use of the World Wide Web by bioinformatics groups, The Web was originally set up by the Eu ropean Centre for Particle Physics (CERN) in Geneva as a method of tra nsferring data between collaborating groups throughout the world, It h as enabled biologists throughout the world to have almost instantaneou s access both to the databases containing the EST sequences and to the automated tools that are required for searching such databases, With such methods we have been able to rapidly identify more than 10 new hu man chemokines from public domain databases, In addition to the known categories of chemokines, which are named C, CC, and CXC based on the spacings of N-terminal cysteine residues, we have been able to identif y the first member of a novel chemokine subfamily, with a novel CXXXC cysteine spacing, Furthermore, we can subdivide the CC chemokines into monocyte chemotactic protein and macrophage inflammatory protein fami lies based on their sequence identity levels, but also their clusterin g on the human genome, as identified on other Web sites, The rapid ava ilability of all this data has reduced the amount of time spent on con ventional gene identification, enabling us to move quickly on to tryin g to understand the biology and physiological relevance of these molec ules, The novel chemokine sequences obtained and alignments with exist ing members of the superfamily are now contained within a Chemokine In formation Source on an open access server, allowing further searching of chemokine sequences and increasing the availability of such data to the scientific community.