(Centrum voor Humane en Klinische Genetica)
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The Mutalyzer project aims to develop an integrated modular package of tools, which should allow users to obtain information about the effect of sequence variants in disease genes. Mutalyzer should assist decision-making in molecular diagnosis based on a sequence change detected in a patient's DNA and prevent misdiagnosis caused by either missing the pathogenic effect of a sequence variant reported as "polymorphic" or, more seriously, reporting a polymorphic change as non-pathogenic.
The Mutalyzer package should perform the analysis of sequence variation effects in several discrete steps. The first and obligatory analysis step is performed by the mutation check module, which should prevent any uncertainty with regard to the position and nature of the sequence change. This module is currently running on the Mutalyzer server and allows the user to check the surrounding sequence and the predicted nature of the sequence change. In the next version, it should ask for confirmation before transfer to the second step of the process, the mutation database check module reported before. This module will check the presence of the sequence change in mutation and SNP (Single Nucleotide Polymorphism) databases. Subsequently, the sequence change will be analyzed by the set of tools for the actual prediction of the sequence variant effect, first on RNA and then on protein level. The sequence variant effect analysis by the Mutalyzer package encompasses different integrated prediction modules, which will consist of existing prediction programs or which will be specifically developed for this project. The modules should predict effects on transcription, RNA processing (splicing, polyA addition), translation, protein processing (structure, folding, modification, localization), and possible interactions with other proteins.
To develop the integrated set of Mutalyzer tools, we are using the object oriented programming language Python in combination with the site-package BioPython, which has been developed specifically for bioinformatics. The advantage of Python is that it is not only easy to learn and read for biologists, but also available as free open source software for different computer platforms, and last, but not least, allows efficient programming (See Eric Raymonds' Why Python article in the Linux Journal). The BioPython site-package contains many useful bioinformatics modules, which can be incorporated in Mutalyzer. These modules provide access to records in sequence, structure, and literature databases (Genbank, Unigene, Swissprot, SCOP, PDB, PubMed) and can deal with different data formats generated by analysis programs (BLAST, FASTA, Clustalw, Expasy). In addition, modules written in other programming languages (BioPerl and BioJava) can be integrated using the BioCorba interface standard. Modification of existing modules should enable access to other databases (i.e. GeneCards, KEGG, Brenda). Nevertheless, some software will need to be developed to transfer the mutation-related data to the relevant web servers and database resources for analysis and queries, to retrieve the results and to present them in a user-friendly manner.
Mutalyzer Development Support
Development of new Mutalyzer functionality is supported by Eurogentest.
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