Integrating Bioinformatics

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Integrating Bioinformatics Medical Informatics

• Genetics in the Clinical Setting

Eric Swanson February 9th, 2005
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What is Bioinformatics

• Genomics
• DNA, sequence, genes
• Landmarks Unique Markers of Sequence
• STS (Sequence Tagged Sites)
• Microsatellite
• SNP (Single Nucleotide Polymorphisms)
• Proteomics
• Protein Structure and Function

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Genetics in the Clinical Setting

• Inherited Factors of Disease
• Screening for Inherited Diseases Before DNA
• Impact of initial DNA Analysis on Clinical
  Setting
• Development of Cheap / Efficient Genetic Tests

• Genotyping for Diagnosis
• Examples PKU, CF, Huntingtons, etc.
• Genotyping for Risk Assesment
• Examples Cancer, Heart Disease
• Movement Toward Uses of Genetic in Tx

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Molecular Genetics Review
Central Dogma Gene to Protein
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Gene Expression Clinical Relevance
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Types of Molecular Data for Clinical Use
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Genetic Variations

• Cyto
• Chromosome numbers
• Duplications, rearrangements, and deletions
• Chromosome
• Sequence Repeats
• Transposable Elements
• Short Deletions, Sequence and Tandem Repeats
  (including microsatellites)
• Nucleotide
• Single Nucleotide Polymorphisms (SNPs)
• Single Nucleotide Insertions and Deletions
  (Indels)

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Genotypes and Genetic Profiles

• Locus an area of sequence of DNA
• Alleles an area of sequence that can differ
• Two Chromosomes Two Alleles / Locus

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Common Nucleotide Mutations
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Genotyping Properties
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Genetic Screening as Common Practice

• Cheap / Efficient Genetic Testing
• Gene/RNA/Protein Arrays
• Gene Chips
• Drug Toxicity Science10.24.03

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Genetic Screening as Common Practice

• Cheap / Efficient Genetic Testing
• Gene/RNA/Protein Arrays
• Gene Chips
• Drug Toxicity Science10.24.03
• Drug Efficacy
• Variable Allele Response

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Genetic Variation and Drug Efficacy
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Polymorphic drug-metabolizing enzymes
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Genetic Screening as Common Practice (Dx AND Tx)

• Patient-Based Therapy (Recognizes Unique Pt)
• Drug Dosage Based on Genetic Profile
• Genetic Databases and Patient Record
• Private Databases
• Public Databases

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SNP Database Examples
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CGAP
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The HapMap project
http//www.hapmap.org/
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NCBI / ENTREZ
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Genetics Informatics Design

• Genetic Data and the Patient
• Research Setting
• Indexed by Patient ID (Patient Subject)
• Genetic Data Linked as Patient Data (Similar to
  Phenotypic, or Other Evaluative Data)
• Clinical Setting Dx vs Tx
• Genetic Screening Currently Only Widely Used for
  Diagnosis
• Research Has Little or No Per-Patient Impact on
  Treatment

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Genetic Research as a Model

• Public Genetic Databases Identify Causative
  Alleles
• Preventative Genetics Already Utilized in some
  areas (Dx only)
• Comparing Patients Genetic Profile?
• Automatic and Immediate Identification of Known
  Risk and Regulative Requirements
• Costs/Benefits of Querying of Public Databases

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Cross-Database Interactivity

• Good Examples Already Exist
• NCBI SNP, OMIM, etc.
• HapMap
• Patient Security is a Concern
• Integrate Public Db
• Storage
• Analysis
• Site Specific
• Patient Identity

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Localized And Site Specific Data Storage

• Large Amounts of Data per Patient
• Site-Based Storage More Probable
• Privacy Concern
• HIPAA Regulation

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HIPAA - Privacy
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Data Storage / Data Sharing

• Large Amounts of Data per Patient
• Site-Based Storage More Probable
• Privacy Concern
• HIPAA Regulation Privacy/Security
• Current Research Labs
• Multi-Center Studies
• Segregation of Personal / Clinical or Genetic
  Information
• Make Ideal Model for Med Info

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Multi-Center Study IBD Genetics
Personal (Identifying) Information And
De-Identifying Information
Thanks to Gillian Bromfield of the NIDDK IBD
Genetics Consortium
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Multi-Center Study IBD Genetics
Thanks to Gillian Bromfield of the NIDDK IBD
Genetics Consortium
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Comments On Phenotypic Data Protocol

• Breadth of Information
• Some feel they don't capture enough info, but
  each center has their own agenda, and so most
  have been collecting additional info using
  additional questionnaires.
• Compliance with Guidelines
• The biggest problem has been uniform use For
  example, appendectomy y/n...many clinicians
  feel it doesn't count if the appendix was
  removed as part of another surgery.  However, we
  decided as group that we would count it as an
  appendectomy any time the appendix is removed.
   We also capture the year of appendectomy, so if
  anyone wants to, they can compare it to year of
  first surgery (often, appendix removal
  accompanies the first surgery an IBD patient
  undergoes).

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Future Concerns

• Cost
• High Throughput Genotyping
• Tech. Equipment Needed For Analysis
• More likely Site Centered or Even Multi-Centered
• Educating Medical Personnel
• Most Testing and Analysis Automatic

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