cellular profiles exploring gene expression profile patterns pathways, profiles and predictions brad...

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Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry Ph. # 628-1956 email [email protected]

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Page 1: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

Cellular Profiles

Exploring gene expression profile patterns

Pathways, Profiles and Predictions

Brad WindleAssociate Professor of Medicinal ChemistryPh. # 628-1956email [email protected]

Page 2: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

Profile

A set of data that reflects something of significance

Cellular Profile

A set of data that reflects something of biological significance

A cell profile- may relate to a property of the cell

A cellular component profile- may relate to a property of the component

Profiles are sometimes referred to as Signatures or Fingerprints

Page 3: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

Cellular Profiles

GeneExpression

ProteinExpression

MiscData

SNPs

Methylation

Cell State

Drug Response

Metabolitics

StructuralGenomic

ProteinStates

Disease

Gene/ProteinSequence

ProteinStructure

DrugStructure

Page 4: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

Cellular Profiles

GeneExpression

ProteinExpression

MiscData

SNPs

MethylationDrug

Response

Metabolitics

StructuralGenomic

ProteinStates

Gene/ProteinSequence

ProteinStructure

DrugStructure

Page 5: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

cell or conditionof interest

control or reference cell

hybridize to microarray

Gene Expression Profiling

Page 6: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

Comparative Genomic Hybridization (CGH)

Structural Genomic Profiling

cell with deletions normal cell

hybridize to metaphase chromosomes

Page 7: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

CGH-arrays

cell with deletions normal cell

hybridize toBAC arrays

Page 8: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

Methylation Profiling

me

me

CGGC Isolate or enrich for methylated DNA

total genomic DNA

Page 9: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

Profiling Transcription Factor-Interactive DNA

Immuno-precipitate w/Ab to protein Chromatin IP or ChIP

total genomic DNA

Page 10: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

Combinatorial Elements Regulating Transcription

Page 11: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

The ProfileData Sources

SNPs DNA microarray, oligos, millions of SNP sites

Protein expression Ab microarray, 2D gels, chromatographics

Protein states 2D gels, <1000 proteins resolved

Drug response brute force, 70,000 compounds screened

Metabolitics chromatographics

DNA/protein sequence Sequencing, <20 people sequenced, brute force

Drug structure in silico

Protein structure 3D crystallography, NMR, brute force

Gene expression DNA microarrays, oligo or PCR, 20-30,000 genes

Structural genomics DNA microarrays, BACs, ~one per 1Mb

Methylation DNA microarrays, upstream sequences, CpG islands

Page 12: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

Gene Expression

Profile

cell lines

genes1

2

3

4

1 2 3 4 5 6 7 8 9

histone modification

histone modification

histone modification

protein synthesis

Page 13: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

http://www.geneontology.org/

Classifying a Gene/Protein’s Function or Pathway

Page 14: Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry

Exploring Gene Expression Profile Patterns

We’ll start with exploring profiles for 6000 genes in theNCI 60 cell lines using the application Treeview.