Bioinformatics and data integration

Coordinator:    Dr. Ralf Herwig
Institution: Max Planck Institut für molekulare Genetik
Goal of the NGFN-plus project was the epigenetic analysis of colon cancer samples from man and mouse and the identification of modifiers responsible for tumor initiation and progression.

The subproject „Bioinformatics and data integration“ was responsible for the theoretical work of the consortium:

1. We substantially extended the meta-database ConsensusPathDB, the most comprehensive collection of human molecular interactions worldwide, to murine interactions. The database allows interpreting genomic data in the context of molecular networks and, thus, functional analysis of the underlying patho-mechanisms [2].

2. We developed a full, one-stop software for the processing and analysis of genome-wide methylation data (MEDIPS, [3]). The requirements for the software were on the one hand robustness in order to cope with the huge amount of data from next-generation sequencing experiments (approx. 1 TB per experiment) and on the other hand specificity in order to extract disease relevant information from these data. All project data were processed through the implemented pipeline, analysed and integrated with other data types such as patient data and transcriptome data. The pipeline was documented and integrated in the statistical software R/Bioconductor as a separate package.

3. Conserved molecular markers in man and mouse were identified based on methylation and transcriptome signals comparing tumor and normal samples [1] and are currently in the process of patenting.

Selected publications:

[1] Grimm C, Chavez L, Vilardell M, Farrall AL, Tierling S, Böhm JW, Grote P, Lienhard M, Timmermann B, Walter J, Schweiger MR, Lehrach H, Herwig R, Herrmann BG, Morkel M (2013) DNA-methylome analysis of mouse intestinal adenoma identifies a tumour-specific signature that is partly conserved in human colon cancer. PLOS Genetics, 9(2):e1003250.

[2] Kamburov A, Stelzl U, Lehrach H, Herwig R (2013) The ConsensusPathDB interaction database: 2013 update. Nucleic Acids Research, 41(Database issue):D793-800.

[3] Chavez L, Jozefczuk J, Grimm C, Dietrich J, Timmermann B, Lehrach H, Herwig R(*), Adjaye J(*) (2010) Computational analysis of genome-wide DNA-methylation during the differentiation of human embryonic stem cells along the endodermal lineage. Genome Research, 20:1441-1450. (*) equal contribution

- ConsensusPathDB meta-database for molecular interactions:
- MEDIPS software:
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