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

mfmiles@vcu.edu

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

Non-biased (semi) Functional Group Analysis: GenMAPP

Mirnics et al., Neuron 28:53, 2000

Microarray Analysis of Gene Expression in Prefrontal Cortex of Schizophrenics

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 Analysis Systematic Explorer -- EASE

http://apps1.niaid.nih.gov/david/upload.jsp

Genome Biol. 2003;4(10):R70. Epub 2003 Sep 11.

EASE -- Options in Analysis

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

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Expression of Aldh9a1 Across BxD RI Lines

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WebQTL Allows Definition of Genetic “Linkage” for Expression Patterns

PAM eQTL on Ch1

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PAM: peptidylglycine alpha amidating monooxygenase

Responsible for amidation of variety of neuropeptides, including NPY

NPY associated with acute responses to ethanol and ethanol drinking behaviors

Correlation of PAM Expression with

Locomotor Activity

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Combining Behavioral and Expression QTL Analyses

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Locomotor activity

SGK expression

Multi-gene eQTL map

Results courtesy of WebQTLwww.webqtl.org (R. Williams, K. Manly et al.)

Expression Networks

Expression Profiling

Pharmacology Genetics

Behavior

Prot-Prot

Interactions

OntologyHomoloGene

BioMed Lit

Relations