Babelomics

Functional interpretation of genome-scale experiments

Barcelona, 28 November de 2007

Ignacio Medinaimedina@cipf.esDavid Montaner

dmontaner@cipf.eshttp://bioinfo.cipf.es

Bioinformatics DepartmentCENTRO 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_at1053_at117_at121_at

1255_g_at1294_at1316_at

.

.1320_at

1405_i_at1431_at1438_at1487_at

1494_f_at1598_g_at160020_at

1729_at1773_at177_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

ENSEMBLwww.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 expressio

n

Cisred

Bioentities

Literature

Gallus gallus

Babelomics imported databases

Babelomics toolsFatiGO: 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_at117_at121_at

1255_g_at1294_at1316_at

.

.

1320_at1405_i_at1431_at1438_at1487_at

1494_f_at1598_g_at160020_at

1729_at1773_at177_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

Gene List1

Gene List2

Organism

Biological process Molecular functionCellular component

KEGG pathwaysBiocarta Pathways (new)

Interpro motifsSwissprot keywords

Bioentities from literature (Marmite)Gene Expression (TMT)

Transcription Factor binding sitesCis-regulatory elements (CisReD)

miRNAs (new)

FatiGO

Text files with a column of identifiers

emailme@cipf.esyour project name

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% Sporulation 20%

Group A Group 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?

84No biosynthesis

26Biosynthesis

BA

FatiGO ResultsGene group1 is enriched in this functional block

Gene group2 is enriched in this functional block

percentages

p-values

corrected p-values

Organism

Gene Listordered

according the

experimentalvalue

FatiScan

Gene1 12.4

Gene2 11.5

Gene3 10.3

Gene4 10.2

Gene5 9.9

Gene6 9.3

Gene7 8.2

Gne8 8.1

Gene10 7.7

gene11 7.4

. .

Biological process Molecular functionCellular component

KEGG pathwaysInterpro motifs

Keywords SwissprotTranscription Factor

Cis-regulatory elements

•Index ranking genes according to some biological aspect under study.

•Database that stores gene class membership information.

•FatiScan searches over the whole ordered list, trying to find runs of functionally related genes.

List of genes

+

-

Annotation label A

Annotation label B

Annotation label CBA 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

% Genes with the specific GO annotation for each partition

Fatiscan results

List of genes

+

-

BA C

% 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

FatiScan ExampleTumor Control

+ t

- t

t ~ Tumor mean expression – Control mean expression

All

gene

s in

the

arr

ay

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