1. Compiling Information and Inferring Useful Knowledge for Systems Biology by Text Mining the Literature Anália Lourenço IBB – Institute for Biotechnology and Bioengineering Centre of Biological Engineering, BioPSE group Universidade do Minho

2. Systems Biology Systems Biology does not investigate individual cellular components at a time, but the behaviour and relationships of all of the elements in a particular biological system while it is functioning. http://www.personal.psu.edu/suk211/blogs/susha nts_blogsphere/2009/07/system-biology-for- personalized-medicine.html

3. Biomedical Literature Mining The idea is to train computers to retrieve, read and interpret the text under processing: – what to read; – how to read; – what to do with the processed text. Roughly speaking, we want to emulate human reading behaviour as closest as possible. – Learning domain-specific behaviour. – Aiming at delivering intuitive, comprehensible domain-specific knowledge.

4. Biomedical Literature Mining Automatic Information Retrieval Automatic Information Retrieval: PubMed bulk access to PubMed contents; full-text documents retrieval of full-text documents; … Automatic Information Extraction Automatic Information Extraction: classification clustering document classification and clustering; relevant information extraction of biologically relevant information; knowledge inference... Bio-entity tagging (mainly genes and proteins) Gene –disease association Protein relations (binary relations and interactions) Function annotation and localization relations Protein sequence (mutations, polymorphisms, modifications) Acronym, synonym and term collection... Enzyme-related information Pharmokinetics Metagenomics...

5. In the Scope of Our Research Group... In sillico Metabolic Engineering Systems Biology Bionformatics Customised end-user applications Heterogeneous data integration Open-source plugins Biomedical LiteratureMining Modelling of Metabolic and Regulatory Networks Modelling of fed- batch fermentation processes Optimization of fed-batch fermentation processes Escherichia coli Helicobacter pylori Saccharomyces cerevisiae Kluyveromyces lactis … Escherichia coli Helicobacter pylori Saccharomyces cerevisiae Kluyveromyces lactis …

6. Genome-scale Model Reconstruction To have a comprehensible knowledge base – Metabolic machinery – Transcriptional regulatory events To be able to perform in silico simulations – In need of a set of balanced reactions => genome-scale model Rocha et al (2007), Gene Ess Gen Scale

7. Work in progress: Genome-scale Model Reconstruction Consolidating knowledge on Escherichia coli K-12 MG1655 The latest E. coli genome-scale metabolic model, iAF1260 EcoCyc contents – Manually curated metabolic data – Regulatory information uploaded from RegulonDB BRENDA contents on specific enzymatic activities – e.g. functional parameters such as K i, K m,... + metabolic regulators + cofactors MPIDB contents on experimentally determined interactions among E. coli proteins Literature – To help in conflict/inconsistency resolution – To add novel information (e.g. information on protein/gene relation to particular stress conditions)

8. Work in progress: Genome-scale Model Reconstruction Reconstructing models for another organisms... Helicobacter pylori Kluyveromyces lactis Streptococcus faecalis

9. Work in progress: Biomedical Literature Mining Mining the bibliome for a systematic review on the stringent response of the bacterium Escherichia coli

10. Work in progress: Biomedical Literature Mining Establishing an Evaluation Baseline for Document Classifiers in Biomedical Curation – the enzyme scenario Where does enzyme information come from? Biocuration

11. Work in progress: Biomedical Literature Mining Lourenço et al. (2010), Expert Systems With Applications, 37(4), 3444–3453. Lourenço et al. (2009), J Biomed Inform. 42(4):710-20. Developing component modules for text mining services for biocuration

12. Work in progress: Network Analysis Developing a framework for the integrated analysis of metabolic and regulatory networks Genetic Regulation Metabolic Transcriptional Regulation Inhibition / Activation A B C D R1 G Promoter TF E2 12 3 Case study: Escherichia coli K-12

13. Work in progress: Optimization Tools OptFlux is an open-source, user-friendly and modular software aimed at being the reference computational tool for metabolic engineering applications. It allows the use of stoichiometric metabolic models for simulation and optimization purposes. www.optflux.org Rocha et al (2010), BMC Syst Biol. 4:45.