Integration of Heterogeneous Informations Sources for Proteomics and Transcriptomics Steffen Möller University of Rostock Proteome Center
Mar 27, 2015
Integration of Heterogeneous Informations Sourcesfor Proteomics and
Transcriptomics
Steffen Möller
University of Rostock
Proteome Center
Data Flow and Motivation
• List of genes products with changed expression level
• Description of variants of genes
Sample A.a
Sample A.1Group A Sample Z.z
Sample Z.1Group Z...
Sample Selection
Preparation
Analysis Measurements
Question
Interpretation
Data available online
• Grouping of samples in homogeneous groups
• Portioning and preparation of samples
• Data derived from a preparation– DNA/RNA sequencing
– Affymetrix Microarrays
– 2DE Gels
– (Tandem) mass spectrometry
• External bioinformatics databases
• Internal extensions to the above– Communication of ideas between researchers
Lab-internalinformation
Measurements
Aids forInterpretation
of Data
Organisation of Samples
Access of MS Spectra
• MASCOT peptide identification
• MS/MS fragment sequencing
Addition to external data sources• Genes discussed among researchers
Overview on Identified Spots on Gel • Integration of Protein expression levels
– Spot Volume– Spot Area– Spot Peak intensity
• with RNA expression levels– from Affymetrix chips
Application of Agent Technology
• Automated retrieval and integration of presumed relevant in-house data
• Assistance in interpretation– Heuristics to extend/shrink list of genes
presumed relevant
• Integration with external online data– Pathways– Known relevance of genes in other diseases
Data Flow
Adapted for Agents:• Input: List of Gene IDs• Output: List of
( Gene ID Agent ID Evaluation Explanation History)
Seed of Genes
ModifiedList of Genes
Heuristic
Examples for Heuristics• Towards extension/shrinking of list of genes under
investigation– Gene lies within chromosomal locus linked to disease
– Chromosomal neighbourhood to other genes of investigation
– Gene is of presumed low abundance
• Guidance of further wet-lab analysis– Comparison of ration RNA/protein levels
• Search for pre- or post-transcriptional control
Example: Interaction with EnsEMBL
• Visualisation of QTLs with expression data(G. Fischer et al. 2002, submitted)
Transfer from Automated Sequence Annotation
• EDITtoTrEMBL (Möller et al. 1998)– Introduction of intermediate level for data integration– Hierarchical organisation of agents
TrEMBL
Program
Program
Integration
EDITtoTrEMBL: Self-introducing Agents
• Dispatchers provide automated planning of annotation path of entries
• Sequence-Analysing agents described their input and their output to dispatching agents
•SWISS-PROT syntax and controlled vocabulary
•Regular expressions as constraints
Application in sequence annotation of transmembrane proteins
• A variety of programs exist to predict– membrane spanning regions– direction of insertion into the membrane
Out
In
Conflict resolution• Implemented with REVISE (C. V. Damasio; 1997)
application described in (S. Möller, M. Schroeder; 2000)
Problems with the transfer of these techniques to the wet-lab
• Analysers cannot describe themselves or their results– No ontology for methods of expression data
analysis has been defined (yet)– The motivation of an analyser to include a gene
cannot be formally expressed
• No rules for conflict resolution applicable– Conflicts point the unexpected, not to artefacts
Discussion• Should I implement the best possible agent system or
rather ASAP hunt for the causing agents of autoimmune diseases?
• New agents are recruited from Perl scripts that are implemented to provide a quick answer to requests of biological researchers.
• Integration on a pragmatical level• The system is accepted by wet-lab researchers.• The system has a PHP-based web-frontend,
– communication between agents is implemented via SOAP– adaptations and extensions to the system are easily
implemented.
AcknowledgementsUniversity of Rostock
Michael Kreutzer, Gertrud Fischer, Bernd Scheidt, Ines Weber, Angelika Allenberg, Björn Damm, Michael Glocker, Hans-Jürgen Thiesen
City University, LondonMichael Schroeder
EMBL-EBI, CambridgeRolf Apweiler
Funded by theBMBF Leitprojekt „Proteom-Analyse des Menschen“
and the Landesforschungsschwerpunkt „Genomorientierte
Biotechnologie“