DIVAS · Domain integrity verification of alternative splicing using statistical methods and molecular modeling
6РП — Действия „Мария Кюри“
- Период
- 2007-03-01 → 2009-02-28
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Алтернативното сплайсване при хората определя как от един ген могат да се създадат различни варианти на един протеин. Анализът на тези варианти помага да се разбере кои промени в структурата на протеина са стабилни и функционални.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - DIVAS (Domain Integrity Verification of Alternative Splicing using statistical methods and molecular modeling)
Using bioinformatics we studied alternative splicing in the human proteome available in the Swissprot database. We analysed 20538 isoforms, i.e. alternative splicing variants of 7101 human genes currently in Swissprot with at least two tentative splice variants. Using statistics, the Pfam domain database, 3D protein structures in PDB, surface energy calculations (with special respect to exposed hydrophobicity) and intrinsic protein disorder predictions we were able to explain all the known existing splice variants currently with experimental evidence in Swissprot (501 splice variants). Expanding this data set to include all the named variants in Swissprot we gained a lot of insight into the nature of alternative splicing and concluded that it is basically governed by two rules: 1. Validated alternative splicing (with a surviving protein isoform) occurs mostly in disordered regions and tends to avoid globular domains; 2. If the splicing does truncate a globular domain it is usually marginal (less than 10% of the domain is removed by the truncation event) or the resulting sub-domain has the characteristics of an intact domain regarding the newly exposed hydrophobic surface area.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The human genome has only about 24,000 protein-coding genes, considerably less than it was previously suspected. Much of the complexity of higher organisms can be attributed to alternative splicing (AS), and more than 70% of human genes are alternatively spliced. However, the number of functional proteins in humans, mice or Drosophila is still entirely uncertain as the putative proteins are identified from nucleic acid sequence information.As there are several databases of AS that contain putative alternative splices assembled from the available EST- and cDNA-based evidence, we are planning to screen these AS isoforms as to whether they have full-length domains and if they can be folded into a stable 3D structure. In the first step we will filter the isoforms with our domain database, which contain only domains, derived from Pfam, that are always full-length (90% of the available Pfam families). In the next step we will mine the annotations of those human Swissprot proteins that have both AS and 3D-structure information, supplemented with orthologous proteins from other organisms and tissue-specific information to create a test set where we can determine with a high level of confidence if the observed splice variants exist in nature or not. We are going to use this test set to generate probabilistic models where we can calculate the probability if a certain AS isoform can exist as a stable isoform. The test set will be also used in evaluating the AS isoform models by structural calculations focusing on the newly discovered connection between alternative splicing and protein disorder. Some calculations will be performed at the High Performance Computing Centre of the University of Szeged in collaboration with theoretical physicists. The added value of this multidisciplinary approach will be hopefully both a better understanding of alternative splicing and the refining of the force fields and local effects used in the molecular modeling of disordered proteins.
Оригинален текст от CORDIS (на английски).
Участници
- INSTITUTE OF ENZYMOLOGY HUNGARIAN ACADEMY OF SCIENCES · BUDAPESTКоординаторНиво градУнгария
Връзки
Данни: CORDIS, © Европейски съюз