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

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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

  • 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


CARS: A Curated Annotation Database Tool


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

(Frontal Cortex)

Distribution of Expressed Genes across Seven Frontal Cortex Comparisons

Percent of ChangeALL FrontalMYELGLUPSYNAPOPCell cycleAlcRes

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

<=-1.90.74.22.01.20.31.11.4

-1.6 to -1.891.98.36.02.01.52.73.3

-1.59 to 1.5994.975.886.093.996.094.792.0

1.6 to 1.891.84.26.02.52.11.22.3

>=1.90.77.50.00.40.20.41.1

Chi-square, p<NA<<0.00010.00020.950.940.930.72

Courtesy of Dr. Adron Harris, UT at Austin


Non-biased (semi) Functional Group Analysis: GenMAPP


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

with Expression Information: PubGen

www.PubGen.org


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 of Aldh9a1 Across BxD RI Lines


WebQTL Allows Definition of Genetic “Linkage” for Expression Patterns


Expression Profiling:

“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

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

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

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


Expression Profiling

Prot-Prot

Interactions

BioMed Lit

Relations

Expression Networks

Ontology

HomoloGene

Genetics

Pharmacology

Behavior


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