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

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


Introduction to dna microarrays functional mining of array patterns

CARS: A Curated Annotation Database Tool


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


Introduction to dna microarrays functional mining of array patterns

Microarray Analysis of Gene Expression in Prefrontal Cortex of Schizophrenics

Mirnics et al., Neuron 28:53, 2000


Introduction to dna microarrays functional mining of array patterns

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

Non-biased (semi) Functional Group Analysis: GenMAPP


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


Introduction to dna microarrays functional mining of array patterns

Efforts to Integrate Diverse Biological Databases

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


Introduction to dna microarrays functional mining of array patterns

Expression of Aldh9a1 Across BxD RI Lines


Introduction to dna microarrays functional mining of array patterns

WebQTL Allows Definition of Genetic “Linkage” for Expression Patterns


Expression profiling

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

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)


Introduction to dna microarrays functional mining of array patterns

Expression Profiling

Prot-Prot

Interactions

BioMed Lit

Relations

Expression Networks

Ontology

HomoloGene

Genetics

Pharmacology

Behavior


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