Briefings in Functional Genomics and Proteomics Advance Access originally published online on February 3, 2006
Briefings in Functional Genomics and Proteomics 2006 4(4):293-294; doi:10.1093/bfgp/eli001
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Editorial
Reader in Functional Genomics School of Biological and Chemical Sciences Queen Mary, University of London Mile End Road, London E1 4NS E-mail: g.elgar{at}qmul.ac.uk
We recently witnessed a huge increase in the number of mammalian genomes that have been made publicly available, from around ten to nearly three hundred. I'm talking of course, of the additional 269 human genomes that have been characterized through the HapMap Consortium, providing additional sequence variation data for each genome across over one million variable base positions. This wonderful resource provides not only an opportunity to carry out high-resolution linkage mapping, but also an opportunity for those of us who dabble in comparative genomics to compare sequence variation within a species with evolutionary rates between species. Constrained positions, that is regions that demonstrate lower variability than neutral ones, and that are also conserved between species, can be flagged as regions of potential function. Additionally, where single nucleotide polymorphisms (SNPs) do occur, but at a low frequency in the population (minor allele frequency of <0.05), these might be considered as potentially detrimental. The second phase of the HapMap project will look to identify and characterize this rarer class of SNP, and will be further enabled by economical sequencing technologies that are targeted towards identifying rare differences in DNA sequence, rather than sequencing the bulk DNA.
We start this issue of ‘Briefings in Functional Genomics and Proteomics’ with a comprehensive and thoroughly referenced review of mass spectrometry (MS) technologies for proteomics. MS has become one of the key technologies in proteomics, and Benito Cañas and colleagues take us on a step-by-step guide through the different approaches, hardware and applications of this versatile and powerful analytical technique. This is an area of rapid recent development, and the field has expanded considerably in the last 15 years. We are taken through a history of MS, from the early developments in peptide mass fingerprinting in the 1990s to the rise of more rapid, high throughput approaches used today. Essential to the development of MS as a technique was, of course, the increasing size of peptide and cDNA databases, allowing peptide and protein identification. The authors give a description of different spectrometry techniques and instruments, pointing out the advantages and disadvantages of each. In addition to describing how proteins are identified through MS, the authors also show how post-translational modifications can be identified. The final sections are devoted to ‘second generation’ proteomics approaches, including gel-free systems that identify hundreds or even thousands of proteins simultaneously. To complement this extensive review, we also include in this issue a technique review on characterizing phosphoproteins and phosphoproteomes using MS.
The second review in this issue, by Frank Hauser and Cornelius Grimmelikhuijzen, illustrates how genomic data can be mined in order to identify and characterize gene families. G-protein-coupled receptors (GPCRs) are a large group of trans-membrane proteins that participate in a host of key processes, and as surface receptors are important vehicles for many ligands. In Drosophila, there are in the region of 50 neuropeptide and protein hormone receptors, and the authors focus on how this large sub-family has been identified and characterized. In many cases, it is necessary to experimentally characterize these receptors, in order to confirm their functional roles. This is because sequence signatures amongst these genes are not always sufficient to allow them to be unequivocally pigeon-holed as one type or another. Candidates are usually screened to test whether they can be activated by specific ligands, and these data can then be compared with the primary sequence. Nevertheless, there are still a number of orphan receptors in the Drosophila genome. The authors discuss some of the difficulties associated with de-orphanizing the remaining twenty or so receptors that have, as yet, no identified ligand association and describe approaches that may overcome these difficulties.
The next review touches on an increasingly popular (perhaps ‘trendy’ is a more appropriate word) theme; that is the exploration of regulatory networks. The concept of pathways and cascades are perhaps too simple to describe the way in which genes interact to regulate one another, so the challenge, particularly in higher organisms, is to be able to define both the networks and the interactions that occur within them. This is an area where mathematical modelling holds great promise. However, Kenneth Kauffman and colleagues point out that, currently, we are limited in biological parameters and data that allow accurate model building. Consequently, the authors describe how accurate and thoughtful experimental design can aid in the daunting task of identifying and characterizing regulatory networks.
The penultimate review, by Peter Langridge and colleagues, reviews how functional genomics approaches have been applied to abiotic stress tolerance in cereals. Clearly, cereal crops are exposed to a variety of unpredictable stresses during their growth cycle, and it is of enormous economical importance to identify genetic factors that influence how well they grow in such conditions. Whilst traditional breeding strategies have had limited success, the availability of functional genomic approaches and model plant species provides an avenue of investigation that may accelerate the identification of genes that play a role in stress response.
The final review of this issue deals with another important practical application of proteomic and genomic technologies in the form of bioremediation. The use of biological agents, such as bacteria or plants, to remove or neutralize contaminants such as in polluted soil or water has long been advocated and indeed is now being championed by conservationists and politicians alike. However, before such schemes can be sanctioned, a much more detailed knowledge of the microbial system is required. Singh and Nagaraj provide an overview of how this can be achieved, and to what extent progress has been made in this area. Given that we have hundreds of complete microbial genomes at our fingertips, the prospects are bright in this important area of waste management.
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