Representing Results of Genetic Tests Using LOINC

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Representing Results of Genetic Tests Using LOINC

• Stanley M. Huff, M.D.Intermountain Health Care
• coshuff_at_ihc.com

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Outline

• The data exchange environment
• HL7 basics
• LOINC basics
• LOINC names for results of genetic tests

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Clinical Integration
IDX (Outpatient) IDX Systems
HELP (Inpatient HIS) 3M
HDM Medrec 3M
ADT, Orders, Results, Billing
Registration, Scheduling
ADT, Billing
Health Data Dictionary 3M
Tuxedo
DataGate Interface Engine STC
ADT, Orders, Results, Billing
ADT, Billing, Case Mix
Billing Financial IHC
ADT, Results, Orders Registration, Scheduling
Tuxedo
DataStage
CIS EMMI/EMR Database (HEMS) 3M
Data Warehouse IHC
Tuxedo
Clinical Workstation 3M
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Why coded data?

• You cant do synchronous decision support on free
  text
• Misspellings
• Homographs (homonyms)
• Multiple terminologies
• Outcomes
• Knowledge discovery
• Knowledge sharing (Arden, GLIF)
• Flexibility in reports
• Data re-use
• Maintenance of the knowledge base

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Typical Clinical Data Flow
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HL7 Lab Result Message
MSH\OADDDADD19941122100053ORUM01 PID
661041GARDNERREEDM PV1IE7703LDS OBR
A000520LYTESSerum Electrolytes OBX1NMNASS
erum Sodium1138mmol/L OBX2NMKSerum
Potassium13.2mmol/L OBX3NMCLSerum
Chloride1114mmol/L OBX4NMCO2Serum
CO2124mmol/L
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OBX the flexible segment
Other data fields include date of observation,
identity of provider giving observation, normal
ranges, abnormal flags
OBXNM11289-6LN38CISOF
A code that
identifies the data in OBX-5(Temp Reading)
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OBX with a coded value
OBXCE11882-8Fetal GenderLNT-D0AA0FemaleSM
I
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So we are all using HL7, what is the problem?

• Site 1
• OBX1CEABOABO GROUPOType O
• Site 2
• OBX1CEBLDTYPABO GROUPTYPEOType O
• Site 3
• OBX1CEABOTYPEABO GROUPOPOSType O

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The goal

• Site 1
• OBX1CE883-9ABO GROUPF-D1250Group O
• Site 2
• OBX1CE883-9ABO GROUPF-D1250Group O
• Site 3
• OBX1CE883-9ABO GROUPF-D1250Group O

Agree on a universal coding system for clinical
observations.
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LOINC Objective
Create universal observation identifiers (test
codes) for use in data exchange standards that
follow a name-value pair strategy (HL7, DICOM,
ASTM, CEN, etc.).
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Important facts

• LOINC 2.08
• 24477 Laboratory LOINC codes
• 5775 Clinical LOINC codes
• LOINC is free for use
• LOINC list servers at www.hl7.org
• Download files and tools from Regenstrief Web
  Site
• www.regenstrief.org/loinc/loinc.htm
• RELMA a tool for mapping local codes to LOINC

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Laboratory LOINC Subject Areas

• Chemistry
• Urinalysis
• Toxicology
• Hematology
• Microbiology
• Antibiotic Susceptibilties
• Immunology/Serology
• Genetic testing

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General Form of LOINC Names

• LOINC codes are created systematically using a
  six axis model

ltcomponentgt ltpropertygt lttiminggt ltsystemgt
ltscalegt ltmethodgt
2947-0 SODIUM SCNC PT BLD QN
The first 5 parts are mandatory, but method is
optional.
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LOINC Names for Genetic Tests
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Objective of GeneTests-LOINC Collaboration

• Initiated summer 2001 (Peter Tarczy-Hornoch MD)
• Goal of the LOINC Committee to develop formal
  names and codes for identifying clinical reports,
  observations, and measurements, including
  laboratory tests, to develop compatible data sets
  for electronic storage, transmission and display
• Goal of GeneTests Catalog and characterize
  available genetic testing and laboratories
  offering these tests
• Goal of Collaboration
• Increase granularity of descriptive test data in
  GeneTests
• Provide data necessary for generation of LOINC
  codes for available clinical genetic tests
  currently not in LOINC
• Automatic linkage (WWW) between relevant LOINC
  and GeneTests database entries

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Collaboration steps

• Development by GeneTests of custom API to access
  selected GeneTests database content for LOINC
  (done)
• Analysis by LOINC of reports and preliminary
  identification of additional data needed for
  LOINC names and codes (done)
• GeneTests pilot poll of clinical labs (in
  process)
• Commercial (n5) academic (n5)
• Request for additional information
• Representative sample reports for all tests
  offered by lab
• Both normal and range of abnormal sample reports
• Scrubbed of patient identifying data
• Joint development of formal methodology
  nomenclature
• Final identification (joint) of data to request
  of labs
• GeneTests solicitation of data from all labs
• Joint establishment of auto-linkage
• LOINC use of API data to generate new
  codes/names

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Nomenclature for Locating Genetic Defects
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List of single letter amino acid codes
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Specific disease gene mutations

• The pattern for the first part of the LOINC name
  is
• ltgene namegt GENE.
• ltmutation nomenclaturegt.
• ltmutation and its locationgt

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Factor V Leiden mutation

• F5 GENE.P.R506Q
• "F5" identifies the gene
• "GENE" is a fixed part
• "P" identifies the kind of mutation nomenclature
  (protein)
• R506Q indicates that the amino acid arginine
  (R) is replaced by glutamine (Q) at codon 506.

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Fully specified names (specific disease genes)

• F5 GENE.P.R506QARBPTBLD/TISSORDMOLGEN
• Synonyms Factor V Leiden, Factor V resistance,
  APC resistance gene
•  HFE GENE.P.C282YARBPTBLD/TISSORDMOLGEN
• Synonyms HLA-H gene, hemochromatosis gene
• CFTR GENE.P. F508 DEL ARBPTBLD/TISSORDMOLGEN
• Synonyms Cystic Fibrosis Transmembrane
  Regulator
• Scale is ORD (ordinal), possible answers are
• no mutation found
• heterozygous mutation (the mutation found in one
  gene)
• homozygous mutation (the mutation was found in
  both genes in the gene pair)

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Reporting of multiple Allels

• APO E Allel 1PRIDPTBLD/TISSNOMMOLGEN
• Synonyms APO E Alzheimer's risk
• Scale is now NOM (nominal)
• Answers E1, E2, E3, or E4
• APO E Allel 2PRIDPTBLD/TISSNOMMOLGEN
• Answers E1, E2, E3, or E4

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Gene Mutation Analysis

• CFTR MUTATION ANALYSIS IMPPTBLD/TISSNOM
  MOLGEN
• Synonyms Cystic fibrosis transmembrane
  regulator
• Answers Identifiable Mutation, Not Identifiable
  Mutation
• BRCA1 MUTATION ANALYSIS IMPPTBLD/TISSNOMMOLG
  EN
• Synonyms breast cancer risk gene
• Answers Identifiable Mutation, Not Identifiable
  Mutation
• CFTR MUTATIONS TESTED FOR PRIDPTBLD/TISSNOMMO
  LGEN
• The answers could include
• Delta F508, G542X, R553X, W1282X, N1303K

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Trinucleotide repeats

• FRAXE GENE.CGG REPEATS ARBPTBLD/TISSORDMOLGE
  N
• Synonym FRAGILE X SYNDROME
• HD GENE.CGG REPEATS ARBPTBLD/TISSORDMOLGEN
• Synonym HUNTINGTON DISEASE, IT15, HD,
  HUNTINGTON CHOREA
• SPINOCEREBELLAR ATAXIA GENES.CAG REPEATS
  ARBPTBLD/TISSORDMOLGEN
• DMPK GENE.CTG REPEATS ARBPTBLD/TISSORDMOLGEN
  
• Synonym MYOTONIC DYSTROPHY
• Scale is ORD with usual answers of
• not expanded
• indeterminate
• expanded

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Gene Rearrangements (hematopathology)

• TCRB GENE REARRANGEMENTS ARB
  PTBLD/TISSORDMOLGEN
• Synonym T cell receptor beta chain
• TCRD GENE REARRANGEMENTS ARB
  PTBLD/TISSORDMOLGEN
• Synonym T cell receptor delta chain
• TCRG GENE REARRANGEMENTS ARB
  PTBLD/TISSORDMOLGEN
• Synonym T cell receptor gamma chain
• Results would be reported as
• clonal, not clonal

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Translocations

• Pattern T(ltbreakpoint gene 1gt,ltbreakpoint gene
  2gt) (ltgene1gt,ltgene2gt)gene translocation
• T(9,22) (ABL1,BCR) GENE TRANSLOCATION
  ARBPTBLD/TISSORDMOLGEN
• Synonyms Philadelphia chromosome, BCR1, chronic
  myeloid leukemia, CML
• T(14,18) (IGH,BCL2) GENE TRANSLOCATION
  ARBPTBLD/TISSORDMOLGEN
• Synonyms Follicular B cell lymphoma, oncogene
  B-cell leukemia 2, CLL, chronic lymphatic
  leukemia, follicular lymphoma
• T(15,17) (PML,RAR) GENE TRANSLOCATION
  ARBPTBLD/TISSORDMOLGEN
• Synonyms RAR, promyelocytic leukemia,
  myelogenous, retinoic acid receptor, acute
  promyelocytic leukemia, APL
• Answers?

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Fraction of cells that have the Rearrangement

• CELLS.T(9,22).(ABL1,BCR)/CELLS TOTAL
  NRFPTBLD/TISSQNMOLGEN
• / represents division
• Scale is QN (quantitative)
• Property is NRF (number fraction)

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Other genetic tests (specifics not shown)

• Identity testing using DNA probes
• Copy number of gene (N-Myc gene, Growth control
  gene)
• Gene loss

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Laboratory LOINC Committee

• Ray Aller, John Baenziger, Pamela D. Banning, Jim
  Bristol, Tom Burgess, Jim Case, Linda Charles,
  Jim Cimino , Diane Dwyer, Arden Forrey, Andy
  Gajda, Norbert Goldfield, Brian Griffin, Ed
  Hazell, Gil Hill, Stan Huff, Kathy Hutchins,
  Kathy Kammerer, Dennis Leavelle, Diane Leland,
  Pat Maloney, Doug Martin, Clem McDonald, Bill
  Meilahn, Karen Sieber, Frank Stalling, John
  Stelling, Bill Thurston, Dan Yokota

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Clinical LOINC Committee

• James Barthel , (Dean Bidgood), Bruce Bray, (Bill
  Francis), Alan Golichowski, Karl Hammermeister,
  James Campbell, Sue Bakken, Pat Wilson, Stan
  Huff, Clem McDonald, Dan Pollock, (Angelo Rossi
  Mori), Jeff Suico, Anders Thurin, Wayne Tracy,
  Barry Gordon, Warren Williams, Pavla Frazier,
  William Karitis, Shaun Shakib, Jim Cimino, James
  Campbell, Susan Matney

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Literature References

• Huff SM, Rocha RA, McDonald CJ, De Moor GJE,
  etal. Development of the LOINC (Logical
  Observation Identifier Names and Codes)
  Vocabulary. Journal of American Medical
  Informatics Association, 1998, 5276-292.
• Dolin RH, Huff SM, Rocha RA, Spackman KA,
  Campbell, KE. Evaluation of a Lexically Assign,
  Logically RefineStrategy for Semi-Automated
  Integration of Overlapping Terminologies.
  Journal of American Medical Informatics
  Association, 1998, 5203-213.
• Rocha RA, Huff SM. Coupling Vocabularies and
  Data Structures Lessons from LOINC. Journal of
  American Medical Informatics Association, AMIA
  Annual Fall Symposium Supplement, 1996, 90-4.
• Forrey AW, McDonald CJ, DeMoor G, Huff SM ,
  Leavelle D, Leland Fiers DT, Charles L, Griffin
  B, Stalling F, Tullis A, Hutchins K, Baenziger J.
  Logical Observation Identifier Names and Codes
  (LOINC) Database A public use set of codes and
  names for electronic reporting of clinical
  laboratory test results. Clinical Chemistry,
  1995.
• Bakken S, Cimino JJ, Haskell R, Kukafka R,
  Matsumoto C, Chan GK, Huff SM. Evaluation of the
  Clinical LOINC (Logical Observation Identifier
  Names and Codes) Semantic Structure as a
  Terminology Model for Standardized Assessment
  Measures. Journal of the American Medical
  Informatics Association, 2000, 7529-538.