Genetics Home Reference: a Consumer Guide to Genomics and Health

1
Genetics Home Reference a Consumer Guide to
Genomics and Health

• Joyce A. Mitchell, PhD
• Professor and Chair
• Department of Biomedical Informatics
• University of Utah

2
Topics Today

• Background
• Human Genome Project and consumers
• Genetics Home Reference
• Focus of the project
• Progress to date
• Some technical details
• Evaluation in brief
• Whats next?

3
Human Genome Project and Consumers
4
Human Genome Project

• International research effort
• Determine DNA sequence
• Began 1990, completed in 2003
• Next steps for 20,000 genes
• Function and regulation of all genes
• Significance of variations in sequence
• Cures, therapies, genomic medicine

5
Health Condition Genes

• 2000 of the 20,000 genes are definitively linked
  to health conditions
• It is a many-to-many relationship.
• Many of these genes interact with environmental
  agents (diet, toxins, drugs, other organisms).

6
The Big Consumer Questions

• What has this Project done for me with my
  disease?
• What information is arising related to human
  health?
• How will this lead to personalized medicine?

7
Consumers Seek Information

• Consumers look online for health information
  about genetic conditions
• Consumers say this information is
• Confusing
• Hard to understand
• Difficult to navigate
• Taylor MR, Alman A, Manchester DK. Use of the
  Internet by patients and their families to obtain
  genetics-related information. Mayo Clin Proc
  2001 76(8) 772-6.

8
Genomics is Impacting Medicine Today!

• 2000 genes health conditions
• 1200 gene tests for diagnosis
• 600 laboratories worldwide
• Relate to diagnosis, therapy, drug dosage,
  occupational hazards, reproductive plans, health
  risks, .

9
Starting Point 11/15/01
10
What is the GHR? http//ghr.nlm.nih.gov/

• An information system focusing on the health
  implications of research arising from the Human
  Genome Project
• Targets the public
• Bridges consumer health information and
  bioinformatics data
• Links to existing resources (NLM and other)

11
Building Bridges
Data Harvesting
Data Harvesting
12
Facts (August 2005)

• Coverage gt 450 topics
• gt 150 conditions
• gt 250 genes
• 23 pair of chromosomes
• gt 95 MedlinePlus topics
• Handbook with 7 chapters
• Expert review

13
Reaching Critical Mass
since Jan 2004
14
Kudos from the Public

• News links from CNN, Nature, Forbes
• Positive feedback
• The best overall reference on human heredity for
  students - from educator
• The first time I have read information that was
  parent friendly... - from parent
• Just what I have been searching for several
  years - from physician

15
DHHS Program Interaction

• Newborn screening
• (HRSA and NICHD)
• Questions from GARD Info Center
• NHGRI Office of Rare Diseases
• NHGRI and NCI cooperation

16
Genetics Home Reference

• Conditions genes chromosome
• Multiple relationships
• Parkinson Disease as an example

• Condition gene chromosome
• Multiple relationships
• Parkinson Disease as an example

17
Genetics Home Reference

• http//ghr.nlm.nih.gov

18
(No Transcript)
19
(No Transcript)
20
Parkinson disease
21
PARK2 Gene
22
Chromosome 6
23
Some Technical Details
24
1. GHR Architecture
HGNC
Entrez Gene
Expert Reviewer
PubMed
GeneTests
ClinicalTrials
.
gov
MedlinePlus
Content
Public
Manager
Publish
Site
Site
Public
Genetics Home Reference System
Content
Developer
25
Many to Many Relationships
Parkinson Disease
Other
Leprosy
associatedwith
causes
predisposes
PARK2
26
Data Sources Map
27
2. Knowledge Source Connections
28
Knowledge Links in GHR
UMLS
Interconnected concepts in UMLS link knowledge
CPT
PDR
MeSH
Others
Gene Ontology
Genes linked to Gene Ontology
Conditions linked to MeSH
Leprosy
PARK2 PRKN2_HUMAN
Parkinson Disease
29
MeSH Bridge
Genetics Home Reference
ClinicalTrials.gov
Parkinson Disease
MedlinePlus
PubMed
MeSH
NLM Gateway
30
3. Content Management

• Change detection
• Gene symbols and names
• ClinicalTrials.gov links
• MedlinePlus topics
• New PubMed references
• Gene Ontology annotations
• Items for annual review

31
4. Translations for the Public

• Example Chromosome Location
• PARK2 at 6q25.2
• GHR
• Translates into a sentence
• Downloads from MapViewer at NCBI
• Creates ideogram and arrow
• Links to GHR handbook for help function

32
Translation
Location Code (from gene prefill) 6q25.2-q27

• Map Ideogram Data (from NCBI)
• chr arm band ISCN-top ISCN-bot bases-top bases-bo
  t stain
• 6 p 25.3b 0 59 1 1015418 gneg
• 6 p 25.3a 60 118 1015419 2030834 gneg
• 6 p 25.3 0 118 1 2030834 gneg
• 6 p 25.2b 118 163 2030835 2796701 gpos
• 6 p 25.2a 164 207 2796702 3562566 gpos
• 6 p 25.2 118 207 2030835 3562566 gpos
• 6 p 25.1c 207 256 3562567 4411616 gneg
• 6 p 25.1b 257 306 4411617 5260666 gneg
• 6 p 25.1a 307 355 5260667 6109715 gneg
• 6 p 25.1 207 355 3562567 6109715 gneg
• p 24.3c 355 419 6109716 7216922 gpos

33
Other Translations

• Semantic expansion for searching
• Spelling suggestions
• Glossary linkages

34
Semantic Expansion

• UMLS Synonyms for Parkinson Disease
• Parkinson Disease
• Idiopathic Parkinson Disease
• Idiopathic parkinsonism
• Lewy Body Parkinson Disease
• Paralysis Agitans
• PARALYSIS AGITANS PARKINSONISM
• parkinson's
• Parkinson's dis
• Parkinson's disease NOS (disorder)
• Parkinson's syndrome
• PD - Parkinson's disease
• Primary Parkinsonism
• Shaking palsy
• Searching for parkinson finds text where
  synonyms are used
• Searching for any synonym is the same as
  searching for parkinson

35
User Evaluations in Brief

• Stay tuned for Dr. Rob Logan.

36
What Next?
37
GHR Long Term Goals

• All MedlinePlus topics with genetic association
• gt150 more
• All simple gene-disease relationships
• 2000 and rising
• More genome health paradigms
• THE Starting Point for genetics health
  information for the public

38
Is This Genomics?

• Or is it Genetics?

39
More Genome Health Paradigms

• Mitochondrial DNA
• Common, complex disorders
• Haplotype/HapMap implications
• Epigenetics
• Pharmacogenomics and genetics
• Nutrigenomics and genetics
• Environmental genomics toxicology
• Diagnostic and therapeutic genomics

40
Pharmacogenetics-new paradigm development

• Focus genehealth condition-drug-diet
• Health condition
• Adverse reaction to arthritis medication
• Adverse reaction to warfarin, etc
• Gene
• CYP2D6, CYP2C9, CYP2C19, CYP3D4, MDR1, etc
• Drug new concept in GHR
• Diet new concept in GHR
• Where to find these new concepts online?
• When does the Amplichip come into play?

41
HapMap

• 10/26/2005
• Consortium Completes HapMap Database Describes
  More Than 1 Million SNP Markers

42
Issues and Opportunities

• Challenges we face
• Large volume of information
• Rapidly changing data
• Annual updates growing larger
• New genetic paradigms to be explored
• Keys for success
• Structured data from data harvesting
• Maps to knowledge resources
• Computer assisted content development
• Automatic summarization
• Question-answering

43
Genetics Home Reference Team

• System Developers
• Jane Fun
• Phillips Wolf
• Nicholas Ide
• John Gillen
• Russell Loane, PhD
• Eric Dorfman
• Senior Advisor
• Joyce Mitchell, PhD

• Content Developers
• Sherri Calvo, MS, MBA
• Cathy Fomous, PhD
• Stephanie Morrison
• Diane Mucci, PhD
• System Evaluators
• Rob Logan, PhD
• May Cheh, MS
• 80 Content Experts

Developed at the National Library of Medicine
44
GHR References

• Mitchell JA, McCray AT, Bodenreider O. From
  phenotype to genotype issues in navigating the
  available information resources. Methods Inf Med.
  200342(5)557-63. PMID 14654891
• Mitchell JA, McCray AT. The Genetics Home
  Reference a new NLM consumer health resource.
  AMIA Annu Symp Proc. 2003936. PMID 14728441
• Mitchell JA, Fun J, McCray AT. Design of
  Genetics Home Reference a new NLM consumer
  health resource. J Am Med Inform Assoc. 2004
  Nov-Dec11(6)439-47. Epub 2004 Aug 6. PMID
  15298997
• Fomous C, Mitchell JA, McCray AT. Genetics Home
  Reference helping patients understand the role
  of genetics in health and disease. Community
  Genetics. 2005, in press.
• Peng Z, Logan RA. Content quality, usability,
  affective evaluation and overall satisfaction of
  online health information. Paper presented at
  Health Communication Division, International
  Communication Association Annual Convention, New
  York, NY, May 2005.
• Mitchell JA, Fomous C, Fun J. Challenges and
  strategies of the Genetics Home Reference. JMLA,
  2005, in review.