1. Babelomics Functional interpretation of genome-scale experiments Barcelona, 28 November de 2007 Ignacio Medina imedina@cipf.es@cipf.es David Montaner dmontaner@cipf.es http://bioinfo.cipf.es Bioinformatics Department CENTRO DE INVESTIGACION PRINCIPE FELIPE (VALENCIA)

2. Babelomics: A systems biology web resource for the functional interpretation of genome-scale experiments. http://babelomics.bioinfo.cipf.es

3. Genome-scale experiment output 1007_s_at 1053_at 117_at 121_at 1255_g_at 1294_at 1316_at.. 1320_at 1405_i_at 1431_at 1438_at 1487_at 1494_f_at 1598_g_at 160020_at 1729_at 1773_at 177_at.. 1007_s_at12.4 1053_at11.5 117_at10.3 121_at10.2 1255_g_at9.9 1294_at9.3 1316_at8.2 1320_at8.1 1405_i_at7.7 1431_at7.4 1438_at6.5 1487_at6.2 1494_f_at5.9 1598_g_at5.8 160020_at4.8 1729_at4.7.... Functional Interpretation

4. ENSEMBL www.ensembl.org Ensembl ID HGNC symbol EMBL acc UniProt/Swiss-Prot UniProtKB/TrEMBL Ensembl IDs RefSeq EntrezGene Affymetrix Agilent PDB Protein Id IPI…. Arabidopsis thaliana Homo sapiens Mus musculus Rattus norvegicus Drosophila melanogaster Caenorhabditis elegans Saccharmoyces cerevisae GO KEGG Interpro Transcription Factors Gene expression Cisred Bioentities Literature Gallus gallus Babelomics imported databases

5. Babelomics tools FatiGO: Finds differential distributions of Gene Ontology terms between two groups of genes. FatiGOplus: an extension of FatiGO for InterPro motifs, pathways and SwissProt KW, transcription factors (TF), gene expression in tissues, bioentities from scientific literature, cis-regulatory elements CisRed. Tissues Mining Tool: compares reference values of gene expression in tissues to your results. MARMITE Finds differential distributions of bioentities extracted from PubMed between two groups of genes. FatiScan: detect significant functions with Gene Ontology, InterPro motifs, Swissprot KW and KEGG pathways in lists of genes ordered according to differents characteristics. MarmiteScan: Use chemical and disease-related information to detect related blocks of genes in a gene list with associated values. GSEA: Detects blocks of functionally related genes with significant coordinate over- or under-expression using the Gene Set Enrichment Analysis. 1007_s_at 1053_at 117_at 121_at 1255_g_at 1294_at 1316_at.. 1320_at 1405_i_at 1431_at 1438_at 1487_at 1494_f_at 1598_g_at 160020_at 1729_at 1773_at 177_at.. 1007_s_at12.4 1053_at11.5 117_at10.3 121_at10.2 1255_g_at9.9 1294_at9.3 1316_at8.2 1320_at8.1 1405_i_at7.7

6. Gene List1 Gene List2 Organism Biological process Molecular function Cellular component KEGG pathways Biocarta Pathways (new) Interpro motifs Swissprot keywords Bioentities from literature (Marmite) Gene Expression (TMT) Transcription Factor binding sites Cis-regulatory elements (CisReD) miRNAs (new) FatiGO Text files with a column of identifiers emailme@cipf.es your project name

7. Testing the distribution of functional terms among two groups of genes (remember, we have to test hundreds of GOs) Biosynthesis 60%Biosynthesis 20% Sporulation 20% Group AGroup B Genes in group A have significantly to do with biosynthesis, but not with sporulation. Are this two groups of genes carrying out different biological roles? 84 No biosynthesis 26 Biosynthesis BA

8. FatiGO Results Gene group1 is enriched in this functional block Gene group2 is enriched in this functional block percentages p-values corrected p-values

9. Organism Gene List ordered according the experimental value FatiScan Gene112.4 Gene211.5 Gene310.3 Gene410.2 Gene59.9 Gene69.3 Gene78.2 Gne88.1 Gene107.7 gene117.4.. Biological process Molecular function Cellular component KEGG pathways Interpro motifs Keywords Swissprot Transcription Factor Cis-regulatory elements

10. Index ranking genes according to some biological aspect under study. Database that stores gene class membership information. Fa tiScan searches o ver the whole ordered list, trying to find runs of functionally related genes. List of genes + - Annotation label A Annotation label B Annotation label C B A C Testing along the ordered list Block of genes enriched in the annotation A Annotation C is homogeneously distributed along the list Block of genes enriched in the annotation B

11. % Genes with the specific GO annotation for each partition Fatiscan results List of genes + - B A C

12. % Genes with the specific GO annotation for each partition GO over- represented among genes over-expressed in A GO over- represented among genes over- expressed in B A B Expression level - + Functional interpretation

13. FatiScan Example TumorControl + t - t t ~ Tumor mean expression – Control mean expression All genes in the array Proliferation Is more associated with the genes on the top of the list Is more associated with the genes that show higher expression in Tumors