dr. dieter maier manchester ontologies workshop 23/24.3.02

Biomax Informatics AG Bioinformatics designed with you in mind.

FunCatTM, a controlled vocabulary encompassing the biology of prokaryotes, plants and animals from

cellular to systemic level

Dr. Dieter Maier

Manchester Ontologies Workshop 23/24.3.02

Biomax Informatics AG, Lochhamer Str. 11, 82152 Martinsried, Germany


Outline

• Objectives

• Structure

• Content

• Development

• Use


Objectives

• Automatic data management

• No prior knowledge of vocabulary required

• Group genes by functional categories

• Extensible

• Organism independent

• Compatible to other ontologies


Disclaimer

what the FunCat is what the FunCat is notnot::

- Tool for the complete description of functions on a Tool for the complete description of functions on a single gene levelsingle gene level


Structure

• Organized hierarchicall

• Related functions grouped on different levels

• Internally consistent

=>=> Provides a data warehouse

- overview about available selection

- progress from general to specific

- infere from specific to general


Hierarchical structure

5´-end 5´-end processingprocessing

rRNA-processingrRNA-processing

tRNA-transcriptiontRNA-transcription

rRNA-transcriptionrRNA-transcription

mRNA-transcriptionmRNA-transcription

mRNA-processingmRNA-processing

TranscriptionTranscription


Content

• Covers cellular processes, systemic physiology, development and anatomy

from procaryotes to the human

• 25 main Categories with ~ 1500 sub-categories

• Categories are independent of organism

• Genes can belong to multiple categories


Metabolism: 247

Energy: 60

Cell cycle and DNA processing: 54

Transcription: 31

Protein synthesis (Translation): 11

Protein fate (folding, modification, destination): 25

Cellular transport: 32

Cellular communication: 47

Cell rescue, defense and virulence: 50

Regulation / interaction with cellular environment: 45

Cell fate: 54

Systemic regulation / interaction with environment : 89

Development (systemic): 51

Transposable Elements, viral and plasmid proteins: 8

Control of cellular organisation: 57

Cell type differentiation: 69

Tissue differentiation: 40

Organ differentiation: 91

Enzymatic activity => EC ~ 4400Protein activity regulation: 23Protein with binding function / cofactor requirement: 49Transport facilitation: 49

Molecular function: 122

Biological process: 1061

Subcellular localisation: 63Cell type localisation: 69Tissue localisation: 41Organ localisation: 91

Localisation: 256


Development

• Historical

• Pathways

• Thesaurus

• Complex relations


Structural development

• Proven flexibility – easy to extend

• Stable overall structure

• Compatibel to other ontologies like- Enzyme Cataloge- Gene Ontology- EcoCyce


Development in numbers

S. cerevisiae 1996

Main categories: 16

Depth: 4

Total: 182

Plant (A. thaliana)and Procaryotes 1998

20

6

528

Animals (Human) 2001

25

6

1448


Integrating Pathways into processes

- hierachical structure allows:- Univocal attribution - Test for completeness- Test for consistence


Integrating additional information

• Create a dynamic ontology from existing ontologies, keywords and linguistic extraction of descriptors from the literature

• Semiautomatic mapping of dynamic ontologie to FunCat


Enabling complex relations

• Intensify multidimensionality

• Enable if ... then ... relations


Use

• Manual annotation

• Automatic annotation

• Data mining


Manual annotation

- multidimensional- stepwise

Four dimensions


Manual annotation

• 17 manually annotated genomes (5 eucaryotes, 12 procaryotes)

• H.sapiens, A.thaliana, S.cerevisiae, N.crassa, propriatary: A.niger

• B.subtilis, T.acidophilum, Listeria, 6 public procaryotes in progress, propriatary: C.glutamicum, C.pneumoniae, 1 undisclosed

• Used for annotation of Transcriptomes


Automatic Annotation

Sequence similarity to manually annotated proteins(distinguish experimentally verified and similarity associated function):

- H. sapiens- A. thaliana- S. cerevisiae- B. subtilis- T. acidophilum


PEDANT Genome Database

Currently more than 170 genomes (600 000 ORFs)

Bacteria Archea Eucarya

Thermotogales

Flavobacteria

Cyanobacteria

Proteobacteria

Gram positives

Greennon-sulfurbacteria

Pyrodictium

Thermoproteus

Methanococcus

Methanobacterium

Methanosarcina Extremehalophiles

EntamoebaSlimemolds

Animals

Fungi

Plants

Ciliates

Flagellates

Trichomonades

Microsporida

Diplomonades


Data mining

• Retrieval

• Visualisation

• Mining

• Integration


Queries using the FunCat: Grouplevel

- Looking for groups of genes:


Single molecule level

- Retrieving protein entries:


The human FunCat

Unclassified

Metabolism

Energy

cell cycle Transcription TranslationProtein fate

Intracellular Transport

Defense

Signalling

Cellphysiology


Comparing genomes

Sequence similairty „ functional homology“

Identification of organism specific functions


Comparing H.sapiens – B.subtilis

0

5

10

15

20

25

30

H.sapiens

B.subtilis

Metabolism

Protein

fate Cellular

communication

Interaction

with cellu

lar

environment


Integrative analysis

Gene expression data

Functionalcatalogue

Functionalcatalogue

Functionalcatalogue

Functionalcatalogue

Protein-proteininteraction data

Protein expression data


Topological clustering (SOM)


Distribution of the genes


Limitations

Co-expression is no proof of functional association.

Integrate evidence from multiple sources.


Integration with annotation

Analyse gene expression data using integration with annotation catalogues.

Functional catalogue

Phenotypes

Interaction


Functional projection


Looking at the gene lists


FunCat

Tool to structure information

Tool to connect information


Thankyou!

dr. dieter maier manchester ontologies workshop 23/24.3.02

Documents

development systemic

cellular environment

cellular communication

cellular transport

cell fate

cell type differentiation

systemic level

systemic physiology