Lesson 13

Functional Genomics II: Functional Databases and

Clustering

Functional Genomic Databases

Gene Ontology - Protein Function

BIND - Protein Interactions

(Biomolecular Interactions Network Database)

KEGG - Biological Pathways

(Kyoto Encyclopedia of Genes and Genomes)

Tyrosine Kinase Function

c-src Function

SH2 - Bind phosphotyrosinesSH3- Bind proline-rich regions Kinases - attach phosphates to other molecules

c-Src Equivalent Logic Gate

Input Output

SH2 Phosphorylated

KinasePhosphorylate

d

SH3Bound

Kinase Activity

Src

c-Src: A Biological Microchip

Tyrosine-kinase transmembrane receptors

Src family tyrosine-kinase binding

Two types of src

1. c-src (cellular src: native to eucaryotic genome)

2. v-src (viral src: rouse sarcoma virus)

v-src infects vertebrate cells and helps cause cancer.

PDGF-Platelet Growth FactorPDGFR-Platelet Growth Factor Receptor Binding

SRC family proteins bind to PDGFR

SH2/SH3 Adaptor Proteins

Gene Ontology

Ontology- Classification scheme

Being

- Word

Gene Ontology Classifications

3 Protein classification schemes:

1. Biological Process - What it does

2. Molecular Function- How it does it

3. Cellular Component- Where it does it

Trees

Parent A

Parent B

Child 1

Child 2

Child 3

Child 4

A child may have only one parent

Directed Acyclic Graphs

Parent A

Parent B

Child 1

Child 2

Child 3

Child 4

A child may have more than one parent

Gap Junctions

Gap Junction Channels

Connexons and Connexins

Hierarchical Clustering: Distances

dxy 1 rxy 2

1 1N

xixi2

i1,N

yiyi2

i1,N

i1,N

2

Hierarchical clustering-Dendrogram and heat map