EBI - SWISS-PROT Software Project Proposals

Project descriptions are still quite rough and preliminary. A more detailed specification will be given (or worked out together with the interested students) before the actual work begins.

All project results (if successful), will actually be used to improve the content and quality of the TREMBL database. Therefore, output quality, reliability, handling of noisy input, and speed are crucial issues.

Inital project coordination and additional biological training will take place during a one week stay at the European Bioinformatics Institute in Hinxton, Cambridge, UK. A similar stay at the end of the project will be focused on project presentation, evaluation and possibly the preparation of a publication.

The corresponding SWISS-PROT entry for this entry is P26150. But for thousands of DDBJ/EMBL/GenBank entries the corresponding SWISS-PROT or TREMBL entries don't exist. The goal of the project is to enable the automatic generation of most of these entries.

Further Reading

• Rolf Apweiler, Alain Gateau, Sergio Contrino, Maria Jesus Martin, Vivien Junker, Claire O'Donovan, Fiona Lang, Nicoletta Mitaritonna, Stephanie Kappus, and Amos Bairoch. 1997. Protein Sequence Annotation in the Genome Era: The Annotation Concept of SWISS-PROT + TREMBL. Proceedings of the Fifth International Conference on Intelligent Systems for Molecular Biology
• Bairoch A., and Apweiler R. 1997. The SWISS-PROT protein sequence data bank and its supplement TREMBL. Nucleic Acids Res. 25:31-36
• Stoesser G., Sterk P., Tuli M.A., Stoehr P.J., and Cameron G.N. 1997. The EMBL Nucleotide Sequence Database. Nucleic Acids Res. 25:7-13.

Programs to be used (among others)

• Sequence Retrieval System V5.x to filter out relevant entries
• The Protein Machine for translation of open reading frames
• Fasta3 to check translation results for reliability

• The BioComputing Hypertext Coursebook, Chapters 1-3

It should be possible to run the program from the command line as well as in interactive mode from a web interface. The interactive mode should also comprise graphic visualisation of the results.

Requirements

Further reading

BioInformatics Services, Rockville, MD 20854 U.S.A., suggests the following project:

Project BIS-1: Computational cDNA Libraries

Project description

Given a genome database, how do we assemble a list of proteins appropriate for construction of cellular level mechanistic models of particular mammalian cell types? From the perspective of bioinformatics, the most useful and practical definition of a cell type is a list of the proteins it expresses. This definition presupposes the central dogma of molecular cell biology:

There are several possible approaches to identifying the proteins that are expressed in a particular cell type. One is the EST approach. It relies on Soares-normalized cDNA libraries obtained from tissues of interest. This approach has two major problems for cell biologists and cell physiologists. First, the tissue samples almost always contain multiple cell types and the normalization procedure guarantees that mRNAs from every cell type will be recorded. Second, even when the original cDNA library is obtained from cultured cells, there is considerable uncertainty as to whether the same genes are expressed in vitro as are expressed in vivo. Moreover, genes expressed in one set of culture conditions may not be expressed in another.

Our project aims to overcome these difficulties by taking advantage of the rapidly increasing information on cell-specific promoter elements. In effect, we propose to construct Computational cDNA (CcDNA) libraries.

This approach has the great advantage that it will be easily generalized to other cell types once promoters have been identified, but we propose to begin with the vascular smooth muscle cell because of its tremendous physiological and pathophysiological significance. The vascular smooth muscle cell is essential for regulation of blood flow to all tissues and organs, as well as control of arterial and venous blood pressure. Aberrant behavior of this cell type is a key feature of atherosclerotic heart disease, hypertension and stroke. In the industrialized world, these diseases account for more deaths and disabilities than any other human affliction.

During the past few years a group of MADS-box transcription factors has been shown to control the expression of muscle-specific genes. In particular, the four members of the myocyte enhancer factor-2 (MEF2) family are expressed in developing cardiac, skeletal and smooth muscle cells. Very recently, Eric Olson's laboratory has identified several potential partners for the MEF2 family that may direct the specific program of vascular smooth muscle differentiation.

We propose to develop a WWW interface to the worldwide genome databases that permits the user to assemble a list of candidate genes containing user-specified upstream promoters or combinations of promoters that are known or hypothesized to control cell-specific expression in vascular smooth muscle. It may also be useful to include promoters that are known to be activated all cell types so as to construct a full computational cDNA (CcDNA) library.

Upon completion of the project we can carry out two tests of its effectiveness. First, we can search the appropriate subsets of dbEST to determine if a significant number of our CcDNAs are known to be expressed in tissues containing vascular smooth muscle. Second, we can compare our list to a list compiled from the joint experience of a large group of investigators working in the fields of vascular smooth muscle cell physiology and cell biology.

Requirements

A working knowledge of elementary molecular cell biology. A good knowledge in C or Perl and knowledge of HTML are highly desirable.

Further Reading

Firulli AB, Olson EN, Modular regulation of muscle gene transcription: a mechanism for muscle cell diversity. Trends Genet 1997 Sep;13(9):364-369

Project LSZ-1: Intelligent Formatting Software for Biosequence Management.