High Performance Proteomics: 7th HUPO Brain Proteome Project Workshop March 7-9, 2007 Wellcome Trust Conference Centre, Hinxton, UK

The Wellcome Trust Conference Centre at Hinxton, UK, was the meeting place of the 7th HUPO Brain Proteome Project Workshop entitled "High Performance Proteomics". It started on Wednesday, March 7, 2007 with a steering committee meeting followed by a two days series of talks dealing with the standardization and handling of tissues, body fluids as well as of proteomics data. The presentation and accompanying vivid discussions created a picture of actual strategies and standards in recent proteomics.     

Wellcome Trust DNA celebration

DNA at 50: The structure of the molecule and its implications has had a major impression on some artists, highlighted in a new exhibition, but its discovery was slow to make an impression. Nigel Williams reports.     

Wellcome Trust/EBI 2009 Meeting Report – Perspectives in Stem Cell Proteomics 22–23 March 2009, Wellcome Trust Conference Centre,Hinxton, UK

This report summarises the recent “Perspectives in Stem Cell Proteomics” meeting that was held at the Wellcome Trust Conference Centre, Hinxton, UK in March 2009. The aim of the meeting was to explore the current status of proteomics in stem cell biology. Several themes encompassing technological and biological studies demonstrated the close relationship that must exist between the two communities in order to maximise our understanding of stem cell behaviour. Highlights included new methods for induction of pluripotent stem cells, new data sets regarding protein expression and phosphorylation dynamics in differentiating cells and the potential for future exploitation in a therapeutic setting.     

Future funding policies from non-government sources: the Wellcome Trust

As we enter the 1990s, the Trust is taking on a new and unsought role as a mainstay of University biomedical research. It is to be hoped that recent statements from Government, which appear to recognize the harm being wreaked on the Universities, will prove to be more than pious platitudes.     

The molecular pathology of haemophilia B. Fourth Wellcome Trust lecture

Haemophilia is a rare inherited disease of blood clotting known since biblical times. The rarer form (haemophilia B) occurs in about 1 in 30,000 males and there are about 900 patients in the U.K. at present. Biochemically, patients either lack or have a defective protein (called factor IX) which is needed for the clotting of blood in response to injury. Only males get the disease. However, females can carry the trait in a latent form and transmit the disease to their offspring. Untreated, the disease leads to internal bleeding into muscles and joints and is life-threatening. In the U.K. and in countries with effective health care programmes, patients are treated by periodic injection of factor IX concentrate, a drug isolated from the pooled plasma derived from many blood donors. This drug replaces their own absent or defective factor IX and allow them to enjoy a relatively normal lifestyle. I have reviewed recent studies on the molecular genetics of haemophilia B which started with the isolation of the gene coding the factor IX protein from normal individuals in 1984. Following this, it has been possible firstly to produce factor IX artificially in the laboratory from cloned copies of the messenger RNA of the factor IX gene. Secondly, it has been possible to improve the diagnosis of 'carriers'. Carrier females often wish to know whether they are carriers or not before they have children. If they are positively identified as carriers, the risk and implications of having a haemophiliac son can be discussed and therapeutic abortion considered.(ABSTRACT TRUNCATED AT 250 WORDS)     

5th BSPR‐EBI Meeting,Proteomics: From Technology to New Biology 8–10 July 2008, Wellcome Trust Conference Centre,Hinxton, Cambridge,UK

This paper reports on the 5^th joint British Society for Proteome Research (BSPR) and European Bioinformatics Institute (EBI) meeting which took place at the Wellcome Trust Conference Centre, Cambridge, UK, from the 8^th to 10^th July, 2008. As in previous years, the meeting attracted leading experts in the field who presented the latest cutting edge in proteomics. The meeting was entitled “Proteomics: From Technology to New Biology” taking into account the major transition proteomics has undergone in the past few years. In particular, the use of multiple reaction monitoring (MRM)‐based targeted experiments for absolute quantification and validation of proteins was the hot topic of the meeting. Attended by some 250 delegates, the conference was extremely well organised and provided a great opportunity for discussion and initiation of new collaborations.     

BSPR/EBI 2007 meeting report--Integrative Proteomics: From Molecules to Systems. July 25-27, 2007 Wellcome Trust Conference Centre, Hinxton, UK.

This report reviews the joint British Society for Proteome Research (BSPR) and European Bioinformatics Institute (EBI) 2007 meeting, 'Integrative Proteomics: From Molecules to Systems' which took place at the Wellcome Trust Conference Centre, Hinxton, UK, from 25th to 27th July. The aim of this year's meeting was to explore how the integration of 'omic' technologies can lead to a comprehensive understanding of cellular organization, differentiation and signalling. Studies investigating protein-protein interactions and trafficking illustrated how the combination of proteomics and bioinformatics is allowing systems biology to develop as a discipline in its own right.     

The 2nd US–Japan DNA Repair Meeting, Honolulu, Hawaii, June 4–8, 2004

The 2nd US–Japan DNA Repair Meeting convened at the JW Marriott Ihilani Hotel, outside Honolulu, Hawaii, from June 4–8, 2004. In keeping with the tradition of US–Japan conferences the meeting was modest in size comprising 25 participants from each country. The program featured platform presentations from each participant, with lots of time devoted to discussion of groups of related talks. A novel feature of the meeting was the absence of formally designated and previously announced titles for sessions and talks, providing a level of informality that promoted relaxed interactions. Discussion was gratifyingly brisk and informative throughout and was considered to be a highlight of the meeting. All sessions were chaired by the program planners Errol Friedberg and Sam Wilson, who did not present formal talks. The following pages comprise summations of the talks presented, organized into primary topic themes.     

Integrating sequence, evolution and functional genomics in regulatory genomics

With genome analysis expanding from the study of genes to the study of gene regulation, 'regulatory genomics' utilizes sequence information, evolution and functional genomics measurements to unravel how regulatory information is encoded in the genome.     

Haplotypic analysis of Wellcome Trust Case Control Consortium data

We applied a recently developed multilocus association testing method (localized haplotype clustering) to Wellcome Trust Case Control Consortium data (14,000 cases of seven common diseases and 3,000 shared controls genotyped on the Affymetrix 500 K array). After rigorous data quality filtering, we identified three disease-associated loci with strong statistical support from localized haplotype cluster tests but with only marginal significance in single marker tests. These loci are chromosomes 10p15.1 with type 1 diabetes (p = 5.1 × 10⁻⁹), 12q15 with type 2 diabetes (p = 1.9 × 10⁻⁷) and 15q26.2 with hypertension (p = 2.8 × 10⁻⁸). We also detected the association of chromosome 9p21.3 with type 2 diabetes (p = 2.8 × 10⁻⁸), although this locus did not pass our stringent genotype quality filters. The association of 10p15.1 with type 1 diabetes and 9p21.3 with type 2 diabetes have both been replicated in other studies using independent data sets. Overall, localized haplotype cluster analysis had better success detecting disease associated variants than a previous single-marker analysis of imputed HapMap SNPs. We found that stringent application of quality score thresholds to genotype data substantially reduced false-positive results arising from genotype error. In addition, we demonstrate that it is possible to simultaneously phase 16,000 individuals genotyped on genome-wide data (450 K markers) using the Beagle software package. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Genetical genomics: the added value from segregation.

The recent successes of genome-wide expression profiling in biology tend to overlook the power of genetics. We here propose a merger of genomics and genetics into 'genetical genomics'. This involves expression profiling and marker-based fingerprinting of each individual of a segregating population, and exploits all the statistical tools used in the analysis of quantitative trait loci. Genetical genomics will combine the power of two different worlds in a way that is likely to become instrumental in the further unravelling of metabolic, regulatory and developmental pathways.     

Biological function made crystal clear - annotation of hypothetical proteins via structural genomics

Many of the gene products of completely sequenced organisms are 'hypothetical' - they cannot be related to any previously characterized proteins - and so are of completely unknown function. Structural studies provide one means of obtaining functional information in these cases. A 'structural genomics' project has been initiated aimed at determining the structures of 50 hypothetical proteins from Haemophilus influenzae to gain an understanding of their function. Each stage of the project - target selection, protein production, crystallization, structure determination, and structure analysis - makes use of recent advances to streamline procedures. Early results from this and similar projects are encouraging in that some level of functional understanding can be deduced from experimentally solved structures.     

Life on top-working@ the Wellcome Trust Centre for Human Genetics: Scotland Yard for DNA detectives

The Wellcome Trust Centre for Human Genetics (WTCHG) was established in 1994 to undertake research into the genetic basis of common diseases. Since June 1999 the centre has been located in the Henry Wellcome Building of Genomic Medicine, University of Oxford. The scientific objective of the centre is to explore all aspects of the genetic susceptibility of disease including the localisation of genes involved in common diseases, characterization of the variants responsible for susceptibility, the understanding of how these DNA variants may contribute to risk of disease in the population and finally, the understanding of how such genetic factors contribute biologically to a disease process. The centre houses multidisciplinary research teams in human genetics, functional genomics, bioinformatics, statistical genetics and structural biology.     

The Collaborative Cross,developing a resource for mammalian systems genetics: A status report of the Wellcome Trust cohort

We report on the progress of a project funded by the Wellcome Trust to produce over 100 recombinant inbred mouse lines as part of the Collaborative Cross (CC) genetic reference panel. These new strains of mice are being derived from a set of eight genetically diverse founders. The genomes of the finished strains will be mosaics of the founder strains’ genomes with a high density of independent recombination breakpoints. The CC mice will be available for distribution free of any intellectual property constraints to serve as a community resource for systems genetics studies.     

ESF Programme on Functional Genomics 1st European Conference: Functional Genomics and Disease 2003

In this report from the 1st European Conference of the European Science Foundation Programme on Functional Genomics, we provide coverage of the high-profile plenary talks and a cross-section of the many presentations in the disease analysis symposia and functional genomics technologies workshops.     

Comparative analysis of comparative genomic hybridization microarray technologies: report of a workshop sponsored by the Wellcome Trust

BACKGROUND: Array-comparative genomic hybridization (CGH), although providing much higher resolution compared with conventional CGH, has not yet become a widely applied method for the analysis of genomic gains and losses. METHODS: In January 2002, the Wellcome Trust sponsored a workshop where many of the laboratories developing this technology met to compare different methodologies for array-CGH. Fourteen groups participated, comprising 11 from Europe and 3 from the United States. To facilitate objective analysis, each laboratory constructed arrays using the same anonymous clones and performed a series of test hybridizations using identical genomic DNAs. RESULTS: A figure of merit (FM) was developed to summarize entire collections of data from each laboratory in a single measurement. The FMs consistently showed that a few groups produced quantitative array hybridization data of high quality, whereas a majority achieved a lower standard. CONCLUSIONS: The conclusions of the workshop were that polymerase chain reaction-based methods for the amplification of large insert clones for arraying were effective for array-CGH. It was also concluded that hybridizations performed under coverslips or in automated hybridization apparatus were less effective than hybridizations performed in simple wells with gentle rocking. A common experience by the participants was the batch-to-batch variability of commercial Cot1 preparations in their ability to suppress hybridization to repeat sequences. (Supplementary material for this article can be found in the online issue, which is available at http://www.interscience.wiley.com/jpages/0196-4763/suppmat/49_2/v49.43.html or at http://www.sanger.ac.uk/HGP/Cytogenetics/Publications/Cytometry Sept 2002/Supplemental.pdf.)     

2004 ASM Conference on the New Phage Biology: the 'Phage Summit'

In August, more than 350 conferees from 24 countries attended the ASM Conference on the New Phage Biology, in Key Biscayne, Florida. This meeting, also called the Phage Summit, was the first major international gathering in decades devoted exclusively to phage biology. What emerged from the 5 days of the Summit was a clear perspective on the explosive resurgence of interest in all aspects of bacteriophage biology. The classic phage systems like lambda and T4, reinvigorated by structural biology, bioinformatics and new molecular and cell biology tools, remain model systems of unequalled power and facility for studying fundamental biological issues. In addition, the New Phage Biology is also populated by basic and applied scientists focused on ecology, evolution, nanotechnology, bacterial pathogenesis and phage-based immunologics, therapeutics and diagnostics, resulting in a heightened interest in bacteriophages per se, rather than as a model system. Besides constituting another landmark in the long history of a field begun by d'Herelle and Twort during the early 20th century, the Summit provided a unique venue for establishment of new interactive networks for collaborative efforts between scientists of many different backgrounds, interests and expertise.