Semiautomatic generation of CORBA interfaces for databases in molecular biology

The amount and complexity of genome related data is growing quickly. This highly interrelated data is distributed at many different sites, stored in numerous different formats, and maintained by independent data providers. CORBA, the industry standard for distributed computing, offers the opportunity to make implementation differences and distribution transparent and thereby helps to combine disparate data sources and application programs. In this thesis, the different aspects of CORBA access to molecular biology data are examined in detail. The work is motivated by a concrete application for distributed genome maps. Then, the different design issues relevant to the implementation of CORBA access layers are surveyed and evaluated. The most important of these issues is the question of how to represent data in a CORBA environment using the interface definition language IDL. Different representations have different advantages and disadvantages and the best representation is highly application specific. It is therefore in general impossible to generate a CORBA wrapper automatically for a given database. On the other hand, coding a server for each application manually is tedious and error prone. Therefore, a method is presented for the semiautomatic generation of CORBA wrappers for relational databases. A declarative language is described, which is used to specify the mapping between relations and IDL constructs. Using a set of such mapping rules, a CORBA server can be generated automatically. Additionally, the declarative mapping language allows for the support of ad-hoc queries, which are based on the IDL definitions

Genome visualisation and user studies in biologist-computer interaction

We surveyed a number of genome visualisation tools used in biomedical research. We recognised that none of the tools shows all the relevant data geneticists who look for candidate disease genes would like to see. The biological researchers we collaborate with would like to view integrated data from a variety of sources and be able to see both data overviews and details. In response to this need, we developed a new visualisation tool, VisGenome, which allows the users to add their own data or data downloaded from other sources, such as Ensembl. VisGenome visualises single and comparative representations of the rat, the mouse, and the human chromosomes, and can easily be used for other genomes. In the context of VisGenome development we made the following research contributions. We developed a new algorithm (CartoonPlus) which allows the users to see different kinds of data in cartoon scaling depending on a selected basis. Also, two user studies were conducted: an initial quantitative user study and a mixed paradigm user study. The first study showed that neither Ensembl nor VisGenome fulfil all user requirements and can be regarded as user-friendly, as the users make a significant number of mistakes during data navigation. To help users navigate their data easily, we improved existing visualisation techniques in VisGenome and added a new technique CartoonPlus. To verify if this solution was useful, we conducted a second user study. We saw that the users became more familiar with the tool, and found new ways to use the application on its own and in connection with other tools. They frequently used CartoonPlus, which allowed them to see small regions of their data in a way that was not possible before

Clinical and genetic heterogeneity of human cataract

Background: Human inherited congenital cataract is phenotypically heterogeneous most likely reflecting a complex underlying genotype. The visual prognosis for childhood cataract of all aetiologies is poor. There is however very limited information about the outcome of patients with isolated congenital cataract. Aims: (1) to establish the phenotypic variability of human inherited cataract (HIC). (2) to determine the visual outcome and surgical complications. (3) to identify and characterise novel genes implicated in cataract. Methods: HIC families were identified from hospital databases. All individuals provided a history and underwent an ocular examination. Linkage analysis, mutation detection and functional analysis of mutations identified were undertaken using appropriate expression systems. Results: (1) 586 individuals (284 affected) from 76 pedigrees participated. Cataract phenotypes could be categorised as one of ten distinct phenotypes. (2) The visual outcome and surgical complication rate was found to be significantly better in our group of isolated cataracts when compared to congenital cataracts of all aetiologies. (3) Novel cataract loci were identified on (a) 12q and different missense mutations in the MIP gene identified in two families. Functional analysis showed that the mutants abolish the water channel function of the protein, (b) 2q. Candidate gene screening of the 2q locus did not reveal a mutation within the y-crystallin gene cluster, (c) Xp. (d) lip. (e) l0q. (f) 11q. (4) Linkage to known cataract loci was excluded in two other families. Conclusions: This study has enabled categorisation of HIC into ten phenotypes. It has shown that patients have better visual and surgical outcomes than those with cataracts of other aetiologies probably due to the lack of attendant developmental abnormalities and because surgery may often be delayed. Four novel cataract loci have been identified. The recognition of mutations in MIP confirms the importance of this protein in both normal lens physiology and cataractogenesis. Furthermore, the functional analyses provide a molecular basis for the cataracts observed

IXDB, an X chromosome integrated database.

The integrated X chromosome database (IXDB) is a repository for physical mapping data of the human X chromosome. Its current content is the result of a strict integration of data stemming from many different sources. The main features of IXDB include a flexible and extendible schema, a comfortable and fully cross-referenced WWW interface (http://ixdb.mpimg-berlin-dahlem.mpg.de ) and a graphical map viewer implemented in JAVA. The database stores objects used in physical mapping as well as the maps resulting from this work, but a strong emphasis is placed on recording experiments that connect objects together. This should greatly contribute to fulfilling one of the major goals of the database: to support the construction of an integrated physical, genetic, transcript and sequence map of the human X chromosome

IXDB, an X chromosome integrated database (update).

Chromosome specific databases are an important research tool as they integrate data from different directions, such as genetic and physical mapping data, expression data, sequences etc. They supplement the genome-wide repositories in molecular biology, such as GenBank, Swiss-Prot or OMIM, which usually concentrate on one type of information. The Integrated X Chromosome Database (IXDB, http://ixdb.mpimg-berlin-dahlem.mpg.de/) is a repository for physical mapping data of the human X chromosome and aims at providing a global view of genomic data at a chromosomal level. We present here an update of IXDB which includes schema extensions for storing submaps and sequence information, additional links to external databases, and the integration of an increasing number of physical and transcript mapping data. The gene data was completely updated according to the approved gene symbols of the HUGO Nomenclature Committee. IXDB receives over 1000 queries per month, an indication that its content is valuable to researchers seeking mapping data of the human X chromosome