Given the scope and the scale of the MitoCheck project, it is of crucial importance to establish a bioinformatics structure to handle data from the consortium and from public sources, and to disseminate the results to the outside world. In this Work Package, we will build on the expertise of our bioinformatics team at the Sanger Institute in handling and displaying large sequencing projects to make the MitoCheck website a unique center for information on mitosis.

- To create and maintain the MitoCheck web-based bioinformatics databases

- To identify proteins important for mitosis based on sequence analysis and homology search

- To design and update primer sets for RNA interference

Richard Durbin (Wellcome Trust Sanger Institute, Hinxton, UK)

Tony Hyman (Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany)

Jan-Michael Peters (Research Institute of Molecular Pathology, Vienna, Austria)

1) Oligo design and sequence analysis of the siRNA library

The siRNA library used in the genome-wide RNAi screen was designed in collaboration with Cenix BioScience GmbH (www.cenix-bioscience.com) and was synthesized by Ambion. (www.ambion.com). It covers all human protein coding genes. Mapping of the siRNAs to transcripts and genes has been completed. This information together with siRNA sequences will be displayed in the MitoCheck website in the near future.

2) Identify proteins required for mitosis based on sequence analysis and homology search

Extensive sequence analysis and homology search have revealed at least 250 genes implicated in mitosis. These genes together with relevant information about them are listed in the MitoCheck database.

3) Web-based MitoCheck bioinformatics databases

The MitoCheck database (http://www.mitocheck.org/cgi-bin/mtc) covers all human protein-encoding genes. Relevant information such as orthologs, protein and mRNA sequences, mutant phenotypes in human cells, subcellular localization and interacting proteins is displayed for each gene if available. More importantly, data generated within the MitoCheck consortium is constantly being incorporated into the MitoCheck database. This includes compressed movies from the genome-wide RNAi screen, cell lines stably expressing tagged mouse genes, protein complex composition and post-translational modifications such as phosphorylation. Currently some of the data are only available to the consortium members. They are due to be released to the public in the near future.

- A systematic comparative and structural analysis of protein phosphorylation sites based on the mtcPTM database.
Jimenez JL, Hegemann B, Hutchins JR, Peters JM, Durbin R. Genome Biol. 2007 May 23; 8(5):R90 (PMID: 17521420)

- [X]uniqMAP: unique gene sequence regions in the human and mouse genomes.
Jimenez JL and Durbin R. BMC Genomics. 2006 Oct 6;7:249. (PMID: 16925840)

- TreeFam: a curated database of phylogenetic trees of animal gene families.
Li H, Coghlan A, Ruan J, Coin LJ, Heriche JK, Osmotherly L, Li R, Liu T, Zhang Z, Bolund L, Wong GK, Zheng W, Dehal P, Wang J, Durbin R (2006) Nucleic Acids Res 34 (Database issue):D572-80 (PMID: 16381935)