Introduction to dna microarrays functional mining of array patterns
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Introduction to DNA Microarrays: Functional Mining of Array Patterns. Michael F. Miles, M.D., Ph.D. Depts. of Pharmacology/Toxicology and Neurology and the Center for Study of Biological Complexity [email protected] 225-4054. Tertiary Analysis: Connecting Function with Expression Patterns.

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Introduction to dna microarrays functional mining of array patterns

Introduction to DNA Microarrays: Functional Mining of Array Patterns

Michael F. Miles, M.D., Ph.D.

Depts. of Pharmacology/Toxicology and Neurology and the Center for Study of Biological Complexity

[email protected]

225-4054


Tertiary analysis connecting function with expression patterns
Tertiary Analysis: Connecting Function with Expression Patterns

  • Annotation

    • UniGene/Swiss-Prot, SOURCE, CARS

  • Biased functional assessment

    • Functional group interrogation

      Manual, GenMAPP, GeneSpring

  • Non-biased functional queries

    • PubGen

    • MAPPFinder, DAVID/Ease, GEPAS, others

    • Cytoscape

  • Overlaying genomics and genetics

    • WebQTL



Tertiary analysis connecting function with expression patterns1
Tertiary Analysis: Connecting Function with Expression Patterns

  • Annotation

    • UniGene/Swiss-Prot, SOURCE, CARS

  • Biased functional assessment

    • Functional group interrogation

      • Manual, GenMAPP, GeneSpring

  • Non-biased functional queries

    • PubGen

    • MAPPFinder, DAVID/Ease, GEPAS, others

    • Cytoscape

  • Overlaying genomics and genetics

    • WebQTL


Microarray Analysis of Gene Expression in Prefrontal Cortex of Schizophrenics

Mirnics et al., Neuron 28:53, 2000


Functional Hierarchy Statistics in Alcoholic Brain Tissue of Schizophrenics

(Frontal Cortex)

Distribution of Expressed Genes across Seven Frontal Cortex Comparisons

Percent of Change ALL Frontal MYEL GLU PSYN APOP Cell cycle AlcRes

(44029) (120) (50) (511) (618) (752) (733)

<=-1.9 0.7 4.2 2.0 1.2 0.3 1.1 1.4

-1.6 to -1.89 1.9 8.3 6.0 2.0 1.5 2.7 3.3

-1.59 to 1.59 94.9 75.8 86.0 93.9 96.0 94.7 92.0

1.6 to 1.89 1.8 4.2 6.0 2.5 2.1 1.2 2.3

>=1.9 0.7 7.5 0.0 0.4 0.2 0.4 1.1

Chi-square, p< NA <<0.0001 0.0002 0.95 0.94 0.93 0.72

Courtesy of Dr. Adron Harris, UT at Austin



Tertiary analysis connecting function with expression patterns2
Tertiary Analysis: Connecting Function with Expression Patterns

  • Annotation

    • UniGene/Swiss-Prot, SOURCE, CARS

  • Biased functional assessment

    • Functional group interrogation

      • Manual, GenMAPP, GeneSpring

  • Non-biased functional queries

    • PubGen

    • MAPPFinder, DAVID/Ease, GEPAS, others

    • Cytoscape

  • Overlaying genomics and genetics

    • WebQTL


Efforts to Integrate Diverse Biological Databases Patterns

with Expression Information: PubGen

www.PubGen.org


Tertiary analysis connecting function with expression patterns3
Tertiary Analysis: Connecting Function with Expression Patterns

  • Annotation

    • UniGene/Swiss-Prot, SOURCE, CARS

  • Biased functional assessment

    • Functional group interrogation

      • Manual, GenMAPP, GeneSpring

  • Non-biased functional queries

    • PubGen

    • MAPPFinder, DAVID/Ease, GEPAS, others

    • Cytoscape

  • Overlaying genomics and genetics

    • WebQTL




Expression profiling
Expression Profiling: Expression Patterns

“It is possible that the expression profile could serve as a universal phenotype … Using a comprehensive database of reference profiles, the pathway(s) perturbed by an uncharacterized mutation would be ascertained by simply asking which expression patterns in the database its profile most strongly resembles … it should be equally effective at determining consequences of pharmaceutical treatments and disease states”

Hughes et al. Cell 102:109-126 (2000)


Use of expression profile compendium to characterize gene or drug function
Use of Expression Profile “Compendium” to Characterize Gene or Drug Function

Key features:

established error model

profiled large number of mutants/drugs under highly controlled conditions

statistical treatment of expression patterns

verified array results with biochemical/phenotypic assays

Hughes et al. Cell 102:109-126 (2000)


Correlation in expression profiles of drugs genes affecting same pathways
Correlation in Expression Profiles of Drugs/Genes Affecting Same Pathways

cup5 and vma8, components of H+/ATPase complex

Unrelated gene mutants

HMG CoA-reductase mutant vs. lovastatin, an inhibitor of HMG2

Red symbols = significant change (p<0.05) in both treatments

Hughes et al. Cell 102:109-126 (2000)


Assigning function to uncharacterized genes by expression profiles
Assigning Function to Uncharacterized Genes by Expression Profiles

Hughes et al. Cell 102:109-126 (2000)


Expression Profiling Profiles

Prot-Prot

Interactions

BioMed Lit

Relations

Expression Networks

Ontology

HomoloGene

Genetics

Pharmacology

Behavior


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