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Babelomics Functional interpretation of genome-scale experiments Barcelona, 28 November de 2007 Ignacio Medina [email protected] David Montaner [email protected] http://bioinfo.cipf.es Bioinformatics Department CENTRO DE INVESTIGACION PRINCIPE FELIPE (VALENCIA) Babelomics: A systems biology web resource for the functional interpretation of genome-scale experiments. http://babelomics.bioinfo.cipf.es 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_at 12.4 1053_at 11.5 117_at 10.3 121_at 10.2 1255_g_at 9.9 1294_at 9.3 1316_at 8.2 1320_at 8.1 1405_i_at 7.7 1431_at 7.4 1438_at 6.5 1487_at 6.2 1494_f_at 5.9 1598_g_at 5.8 160020_at 4.8 1729_at 4.7 . . . . Functional Interpretation Babelomics imported databases GO Homo sapiens Mus musculus KEGG Rattus norvegicus Interpro Transcription Factors Ensembl ID Gallus gallus ENSEMBL www.ensembl.org Cisred Drosophila melanogaster Saccharmoyces cerevisae Arabidopsis thaliana Gene expression EMBL acc UniProt/Swiss-Prot UniProtKB/TrEMBL Ensembl IDs RefSeq EntrezGene Affymetrix Agilent PDB Caenorhabditis elegans Bioentities Literature HGNC symbol Protein Id IPI…. Babelomics tools FatiGO: Finds differential distributions of Gene Ontology terms between two 1007_s_at 1320_at groups of genes.1053_at 1405_i_at 117_at 1431_at FatiGOplus: an extension of FatiGO for InterPro motifs, pathways and 121_at 1438_at SwissProt KW1255_g_at , transcription factors 1487_at (TF), gene expression in tissues, 1294_at 1494_f_at cis-regulatory elements CisRed. bioentities from scientific literature, 1316_at 1598_g_at . 160020_at Tissues Mining Tool: compares reference values of gene expression in . 1729_at tissues to your results. 1773_at 177_at MARMITE Finds differential distributions of bioentities extracted from PubMed . between two groups of genes. . 1007_s_at 12.4 FatiScan: detect significant functions with Gene Ontology, InterPro motifs, 1053_at 11.5 Swissprot KW and KEGG pathways in lists of genes ordered according to differents characteristics. 117_at 10.3 121_at 10.2 MarmiteScan: Use chemical and disease-related information to detect related 1255_g_at 9.9 blocks of genes in a gene list with associated values. 1294_at 9.3 8.2 GSEA: Detects blocks of functionally related genes 1316_at with significant coordinate 1320_at 8.1 over- or under-expression using the Gene Set Enrichment Analysis. 1405_i_at 7.7 FatiGO Organism Text files with a column of identifiers Gene List1 Gene List2 [email protected] your project name 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) Testing the distribution of functional terms among two groups of genes (remember, we have to test hundreds of GOs) Group A Group B Are this two groups of genes carrying out different biological roles? Biosynthesis 60% Biosynthesis 20% Sporulation Sporulation 20% Genes in group A have significantly to do with biosynthesis, but not with sporulation. Biosynthesis No biosynthesis A 6 4 20% B 2 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 FatiScan Organism Gene List ordered according the experimental value Gene1 12.4 Gene2 11.5 Gene3 10.3 Gene4 10.2 Biological processGene5 Molecular functionGene6 Gene7 Cellular component KEGG pathways Gne8 Interpro motifs Gene10 gene11 Keywords Swissprot . Transcription Factor Cis-regulatory elements 9.9 9.3 8.2 8.1 7.7 7.4 . Testing along the ordered list Annotation label A List of genes •Index ranking genes according to some biological aspect under study. + A B C Annotation label B Annotation label C Block of genes enriched in the annotation A •Database that stores gene class membership information. Annotation C is homogeneously distributed along the list •FatiScan searches over the whole ordered list, trying to find runs of functionally related genes. - Block of genes enriched in the annotation B Fatiscan results List of genes + A B C % Genes with the specific GO annotation for each partition Functional interpretation A B + Expression level GO overrepresented among genes over-expressed in A GO overrepresented among genes overexpressed in B % Genes with the specific GO annotation for each partition FatiScan Example Tumor Control t ~ Tumor mean expression – Control mean expression All genes in the array +t -t 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