Research Report 2003 - Max-Planck-Institut für molekulare Genetik

Department of Vertebrate Genomics
20
b) DNA expression profiling
Our group has carried out data analysis service for more than 20 projects from 10
different groups within and outside the department. Different technologies (Affymetrix,
glass-chips, nylon-arrays) have been incorporated in the data analysis modules. Research
covers the full pipeline from image analysis, normalisation, cluster analysis,
reverse engineering and modelling and simulation.
c) “Meta-clustering”
We set up a framework to compare and validate various clustering methods for gene expression
profiles. Since the concept of co-regulation is fundamental to large gene expression screenings
and since each individual method has a certain bias we focus on validation methods for gene
expression clusters by robust normalisation of the data, by the comparison of different methods,
by the definition and implementation of numerical cluster validation methods and the comparison
of gene expression data to alternative data sources. A graphical user interface to a comprehensive
data-mining tool, BioMiner, has been set up in close collaboration with the bioinformatics
start-up MicroDiscovery GmbH Berlin.
d) Data integration
We define methods and strategies to correlate and integrate data from various sources into
a unifying gene-based concept. As an example we correlated data from EST-mining, RT-
PCR and whole-mount in-situ hybridisations from mouse orthologues to human chromosome
21 genes. Further attempts are ongoing with the AG Yaspo to validate EST-mining
data and gene expression data. In order to take into account transcriptional regulation we
work on a joined project with the Department of Computational Biology (Prof. Vingron)
in order to evaluate gene expression data and transcriptional profiling data coming from
comparative cross-species sequence analysis.
e) Statistical service
The bioinformatics group has contributed to the statistical evaluation of other data sets such as
the comparative analysis of the 2R hypothesis, the analysis of peptide peak-lists derived from
2D-gels (AG Gobom) and the large-scale sequence analysis of bacteria genomes (AG Russo).
f) Simulation and Modelling
Modelling and simulation systems are a valuable tool for the understanding of complex systems.
We developed an object-oriented environment, PyBioS, that is able to process such systems.
In the context of array hybridization experiments we used this system for the simulation of
artificial gene expression data in order to identify and validate important experimental parameters.
In collaboration with the Kinetic modeling group (AG Klipp) we established a modeling
platform for in-silico experiments in the context of target validation.
g) Visualisation
We develop tools for data quality control and visualisation. The program Xdigitise was
designed for the visualisation and manipulation of TIF-images in order to check image
analysis results. The automated image analysis program, FA, for hybridisation images has
been developed and successfully applied to various projects. Furthermore, we are developing
the Java tool A-Cgen for the purpose of array data quality control. This tool is
implemented in the chip-processing pipeline that we set up with the automation group
(AG Hultschig). We currently implement modules for data quality control, normalisation
and the detection of differentially expressed genes. Furthermore, the tool allows webconnections
to data resources such as GenomeMatrix, Entrez server and Ensembl.
Sequence Analysis (Hennig)
The main research areas and activities of our group are evolutionary sequence analysis,
generalized sequence annotation based on GeneOntology, clustering of redundant
cDNA sequences (ESTs), species-species comparison in terms of orthology, and
the development of automatic high-throughput procedures for genome annotation.