Title: Integrating Bioinformatics
1Integrating Bioinformatics Medical Informatics
- Genetics in the Clinical Setting
Eric Swanson February 9th, 2005
2What 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
3Genetics 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
4Molecular Genetics Review
Central Dogma Gene to Protein
5Gene Expression Clinical Relevance
6Types of Molecular Data for Clinical Use
7Genetic 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)
8Genotypes and Genetic Profiles
- Locus an area of sequence of DNA
- Alleles an area of sequence that can differ
- Two Chromosomes Two Alleles / Locus
9Common Nucleotide Mutations
10Genotyping Properties
11Genetic Screening as Common Practice
- Cheap / Efficient Genetic Testing
- Gene/RNA/Protein Arrays
- Gene Chips
- Drug Toxicity Science10.24.03
12Genetic Screening as Common Practice
- Cheap / Efficient Genetic Testing
- Gene/RNA/Protein Arrays
- Gene Chips
- Drug Toxicity Science10.24.03
- Drug Efficacy
- Variable Allele Response
13Genetic Variation and Drug Efficacy
14Polymorphic drug-metabolizing enzymes
15Genetic 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
16SNP Database Examples
17CGAP
18The HapMap project
http//www.hapmap.org/
19NCBI / ENTREZ
20Genetics 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
21Genetic 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
22Cross-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
23Localized And Site Specific Data Storage
- Large Amounts of Data per Patient
- Site-Based Storage More Probable
- Privacy Concern
- HIPAA Regulation
24HIPAA - Privacy
25Data 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
26Multi-Center Study IBD Genetics
Personal (Identifying) Information And
De-Identifying Information
Thanks to Gillian Bromfield of the NIDDK IBD
Genetics Consortium
27Multi-Center Study IBD Genetics
Thanks to Gillian Bromfield of the NIDDK IBD
Genetics Consortium
28Comments 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).
29Future 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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