Biomedical subjects
Publications and source records attributed to Michael Hamacher.
More than 70 interested colleagues attended the 4(th) Workshop of HUPO's Brain Proteome Project. The project was presented within nine talks mainly focusing on two running pilot studies as well as on data re-processing. A bioinformatics jamboree in Hinxton, UK, and the 5th Workshop taking place in Dublin next February were announced.
The Bioinformatics Committee of the HUPO Brain Proteome Project (HUPO BPP) meets regularly to execute the post-lab analyses of the data produced in the HUPO BPP pilot studies. On January 9-11, 2006 the members as well as invited analysts came together at the European Bioinformatics Institute in Hinxton, UK for the pilot studies jamboree. The results of the reprocessing were presented and tasks forces were initiated to compile, to interpret and to summarise the data obtained.
The Human Proteome Organisation Brain Proteome Project aims at coordinating neuroproteomic activities with respect to analysis of development, aging, and evolution in human and mice and at analysing normal aging processes as well as neurodegenerative diseases. Our group participated in the mouse pilot study of this project using two different 2-DE systems, to find out the optimal conditions for comprehensive gel-based differential proteome analysis. Besides the assessment of the best methodical conditions the question of "How many biological replicate analyses have to be performed to get reliable statistically validated results?" was addressed. In total 420 differences were detected in all analyses. Both 2-DE methods were found to be suitable for comprehensive differential proteome analysis. Nevertheless, each of the methods showed substantial advantages and disadvantages resulting in the fact that modification of both systems is essential. From our results we can draw the conclusions that for the future optimal quantitative differential gel-based brain proteome analyses the sample preparation has to be slightly changed, the resolution of the first as well as the second dimension has to be advanced, the number of experiments has to be increased and that the 2D-DIGE system should be applied.
More than 70 interested colleagues attended the 5th Workshop of the HUPO Brain Proteome Project (HUPO BPP) at the UCD Conway Institute, Dublin, Ireland. An overview of the outcome of the pilot study was presented and the new subprojects "Clinical Neuroproteomics of Human Body Fluids" as well as "Cerebellum 2D-mapping" were announced. In addition the election of the HUPO BPP committees and the future directions of this project were discussed and decided. The meeting was enhanced by several talks highlighting the application of proteomics in biomedical research.
The HUPO Brain Proteome Project is an initiative coordinating proteomics studies to characterise human and mouse brain proteomes. Proteins identified in human brain samples during the project's pilot phase were put into biological context through integration with various annotation sources followed by a bioinformatics analysis. The data set was related to the genome sequence via the genes encoding identified proteins including an assessment of splice variant identification as well as an analysis of tissue specificity of the respective transcripts. Proteins were furthermore categorised according to subcellular localisation, molecular function and biological process, grouped into protein families and mapped to biological pathways they are known to act in. Involvement in pathological conditions was examined based on association with entries in the online version of Mendelian Inheritance in Man and an interaction network was derived from curated protein-proteininteraction data. Overall a non-redundant set of 1804 proteins was identified in human brain samples. In the majority of cases splice variants could be unambiguously identified by unique peptides, including matches to several hypothetical transcripts of known as well as predicted genes.
The pilot phase of the Brain Proteome Project (BPP), the Human Proteome Organization (HUPO) initiative that focuses on studies of the brain of both humans and mice, has now been completed. Participating laboratories studied the proteomes of two human samples derived from biopsy and autopsy as well as three mouse samples from various developmental stages. With the combined and centrally reprocessed data now available, a comparison in terms of protein identifications and project organization is made between the HUPO BPP pilot and three other proteomics studies: the HUPO Plasma Proteome Project (PPP) pilot, a proteome of human blood platelets and a recently published comprehensive mouse proteome. Finally, as any comparison between large-scale proteomics datasets is decidedly non-trivial, we also evaluate and discuss several ways to go about comparing such different result sets.
The newly available techniques for sensitive proteome analysis and the resulting amount of data require a new bioinformatics focus on automatic methods for spectrum reprocessing and peptide/protein validation. Manual validation of results in such studies is not feasible and objective enough for quality relevant interpretation. The necessity for tools enabling an automatic quality control is, therefore, important to produce reliable and comparable data in such big consortia as the Human Proteome Organization Brain Proteome Project. Standards and well-defined processing pipelines are important for these consortia. We show a way for choosing the right database model, through collecting data, processing these with a decoy database and end up with a quality controlled protein list merged from several search engines, including a known false-positive rate.
The Human Proteome Organisation (HUPO) initiated several projects focusing on the proteome analysis of distinct human organs. The Brain Proteome Project (BPP) is the initiative dedicated to the brain, its development and correlated diseases. Two pilot studies have been performed aiming at the comparison of techniques, laboratories and approaches. With the help of the results gained, objective data submission, storage and reprocessing workflow have been established. The biological relevance of the data will be drawn from the inter-laboratory comparisons as well as from the re-calculation of all data sets submitted by the different groups. In the following, results of the single groups as well as the centralised reprocessing effort will be summarised and compared, showing the added value of this concerted work.
Within the pilot phase of the HUPO Brain Proteome Project, nine participating laboratories analysed human (epilepsy and/or post mortem material) and mouse brain samples (embryonic, juvenile and adult), respectively, using a variety of different state of the art techniques. Thirty-seven different analytical approaches were accomplished. Of these analyses, 17 were done differentially, i.e. the protein expression patterns of the different samples (human or mouse) were compared. A catalogue of all proteins present in the respective sample was built in 20 analyses (mapping). All data were collected in the Data Collection Center in Bochum, Germany, and were reprocessed according to thoroughly defined parameters. In this report, a summary of all results and inter-laboratory comparisons with respect to the number of identified proteins, the analysed organism, and the used techniques is presented.
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More than 1200 attendees came together at the 3(rd) HUPO World Congess in Beijing, October 25-27, 2004. In numerous different sessions the wide range of proteomic areas became visible. The HUPO Brain Proteome Project (HUPO BPP) organized an evening session on October 23, presenting the first results of two pilot studies as well as the newest, very positive international development in this field. The rising importance became even more apparent in the plenary presentation of all HUPO initiatives and the following congress activities.
The data acquisition phase of initial pilot studies (human and mouse brain samples) of the Human Proteome Organisation (HUPO) Brain Proteome Project (BPP) is now complete and the data generated by the participating laboratories has been submitted to the central Data Collection Center. The BPP Bioinformatics Group met on 8th April 2005 at the European Bioinformatics Institute (Hinxton, UK) to discuss strategies for the reanalysis of the pooled data from all the participating laboratories. A summary of the results of the data reprocessing will be presented at the 4th HUPO World Congress that will be held in August/September 2005.
The HUPO Brain Proteome Project met during the 4th Dutch Endo-Neuro-Psycho Meeting in Doorwerth, The Netherlands, on June 1, 2005, in order to discuss appropriate (mouse) models for neurodegenerative diseases as well as to conceptualise sophisticated proteomics analyses strategies. Here, the topics of the meeting are summarised.
The Bioinformatics Committee of the HUPO Brain Proteome Project (HUPO BPP) meets regularly to execute the post-lab analyses of the data produced in the HUPO BPP pilot studies. On July 7, 2005 the members came together for the 5th time at the European Bioinformatics Institute (EBI) in Hinxton, UK, hosted by Rolf Apweiler. As a main result, the parameter set of the semi-automated data re-analysis of MS/MS spectra has been elaborated and the subsequent work steps have been defined.
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The brain is complex, and so are the proteomics studies of brain tissue and its diseases, including Alzheimer's Disease, Parkinson's Disease and schizophrenia. In this review, general considerations and strategies of proteomics technologies, the advantages and challenges as well as the special needs for brain tissue are described and summarized. In addition, the results of the first studies are presented including a quality evaluation of the candidate proteins for these diseases. A paragraph is dedicated to the efforts of standardization in this field.
The second Human Brain Proteome Project (HBPP) Workshop of the Human Proteome Organisation (HUPO) took place at the Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI) from April 23-24, 2004. During two days, more than 70 attendees from Europe, Asia and the US came together to decide basic strategic approaches, standards and the beginning of a pilot phase prior to further studies of the human brain proteome. The international consortium presented the technological and scientific portfolio and scheduled the time table for the next year.
The pilot phase of the Human Brain Proteome Project as a part of the Human Proteome Organisation has just been started. In two pilot studies, 18 different laboratories are analyzing mouse brains of three age stages and human brain autopsy versus biopsy material, respectively. The overall aim is to elucidate the portfolio of available techniques as well as to elaborate common standards. As a first step, it was decided to use the common bioinformatics platform ProteinScape that was introduced to the participating groups in a two day course in Bochum, Germany.