Prostacyclin Synthase Overexpression Prevents Mouse Lung Carcinogenesis

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Effect of Alcohol on Brain Development
Normal
Fetal Alcohol Syndrome
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• Defining cognitive disorders
• by gene expression profiling
• Examples of cognitive disabilities
• Mental illness
• Mental retardation
• Alzheimers and other dementia
• Traumatic brain injury
• Stroke
• Fetal Alcohol Syndrome
• Gene profiling provides a
• molecular fingerprint for susceptibility
• and cause of specific cognitive disorders.

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Microarray Expression Profiling for
Understanding Cognitive Disabilitites

• Defining the human genome provides the database
  for
• profiling gene expression patterns in cognitive
  disabilities.
• Specific cognitive disabilities will not be a
  single disorder
• but rather multiple disorders that manifest
  themselves
• with a common medical diagnosis.
• Gene array technology allows defining the
  spectrum of
• gene expression profiles for normal
  individuals and those
• with specific cognitive disorders.
• Gene profiling allows molecular fingerprinting
  of an
• individuals cognitive disorder.

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The Role of Informatics in Addressing Cognitive
Deficits

• Neuroinformatics
• Integrating data from behavioral, physiological,
  anatomical, cellular and molecular levels
• Building and testing neural models in silico
• Molecular bioinformatics
• Analysis of genes, gene expression arrays, etc.
• Modelling metabolic and signalling pathways
• General bioinformatics
• Organizing, managing and extracting relevant
  information from the biological literature.

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Integrating Diverse Sources of Data

• Relevant information is available from many
  sources, none designed to be interoperable
• We have designed and implemented systems that use
  automated ontologies and advanced database
  technology to integrate diverse data from
• public and private databases
• multiple institutions
• multiple biological data types (e.g. QTLs gene
  expression arrays)

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Finding Patterns and Relationships

• Machine learning using data and computation to
  extend human intuition and statistical power
• HSC bioinformatics invents new techniques, and
  has a powerful kit of existing tools
• Neural networks
• Support vector machines
• Information theory (e.g. mutual information)
• Bayesian inference

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Predictive Modelling in Complex Biological
Systems

• Biological systems are inherently non-linear
  combinations and relationships are key
• High-throughput revolution (e.g. gene expression
  arrays) creates enough data for pattern discovery
• Sample applications
• Found a 4 gene combination that distinguishes
  among leukemias as well as 50 gene linear model
• Combined 3 weak alcohol state markers into a
  near-perfect predictor from 1800 training
  examples.

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