Transcript MP - IHTSDO Tooling

An extended SNOMED CT
concept model for
observations in molecular
genetics
James R. Campbell MDac
Geoffrey Talmon MDad
Allison Cushman-Vokoun MD PhDa
Daniel Karlsson PhDbc
W. Scott Campbell PhDad
aDepartments
of Internal Medicine and Pathology
University of Nebraska Medical Center
bDepartment of Biomedical Engineering; Linkoping University;
Linkoping, Sweden
CObservables
Project Group and diPALM SIG; IHTSDO
Outline
 Terminology challenges created by Personalized
Medicine
 What is an ‘Observable entity? Where do they fit
in the SNOMED CT concept model? …the ONC
terminology model?
 LOINC – SNOMED CT harmonization model for
observable entities
 Anatomic and molecular pathology project at
UNMC …Application of the harmonized model to
genomics and molecular pathology?
 Where do we go from here?
Revolution in healthcare
Sequencing of human genome has led to
flood of new observational data appearing in
scientific literature and now…clinical records
Majority of this clinical data is unstructured
and not useful for decision support in the EHR
or clinical research
Understanding of genetic and molecular basis
of human disease now having impact on
therapy
 Challenge for precision medicine - to have
sufficiently detailed molecular genetics
observations and diagnostic data for clinical
care and research
Limitations of ONC terminologies for
observables in molecular pathology
Research community
 NCBI: Gene Ontology; HGNC; OMIM; Orphanet; Protein Ontology;
Cell ontology
Clinical community
 SNOMED CT:
– No concept model for subcellular anatomy (genes) or
molecular structure (proteins)
– No concept model for Observable entity or molecular basis of
disease in Clinical findings
– Little content
 LOINC 2.54:
– 1275 PCR; 1406 MOLGEN; 116 FISH; 1502 CELL MARKERS
– LOINC defining attributes inadequate to fully specify what is
being resulted
– Provides only tag-level interoperability of molecular data
 No meaningful bridge joining genetic research findings with clinical
concept models
Observable entity?
IHTSDO
“Observables are considered to be partial observation results,
where there is a defined part of the observation missing.”
“Concepts in this hierarchy can be thought of as representing a
question or procedure which can produce an answer or a
result”
“Observable + Evaluation (test) result = Finding”
Regenstrief institute
“…a set of universal names and ID codes for identifying
laboratory and clinical test results”
“…master file of standard ‘test’ names and codes that will
cover most of the entries in these files of operational laboratory
systems”
“…organization of LOINC is divided first into four categories,
‘lab’, ‘clinical’ ‘attachments’ and ‘surveys’ ”
LOINC – SNOMED CT
Harmonization of
Observable entities
 2008 agreement between Regenstrief (RI) and
IHTSDO
https://loinc.org/collaboration/ihtsdo/agreement.pdf
– Extend and harmonize a shared concept model for
363787002|Observable entity|
– Map and instantiate LOINC parts in SNOMED CT
content
– Jointly publish expression data set defining (lab)
LOINC concepts within the harmonized concept
model
– Technology preview alpha January 2016
 Assertion: What is needed to support clinical decision
making and research in molecular genetics is a unified
domain ontology for Observable entities spanning
clinical and research content including genomics
MP: Domain ontology
Terminology Use Cases
Retrieve all colon cancer tissue specimens
which had BRAF gene testing (IHC or
sequencing)
Retrieve all breast cancer cases that
tested ER-, PR- and Her2/NeuIdentify all colon cancer cases with high
degree microsatellite instability by PCR or
absence of mismatch repair protein by IHC
Identify all cases with Stage IIIa non-small
cell lung cancer that had EGFR mutation
testing by any method
UNMC: Project for structured
encoding of AP/MP cancer reports
Objective: Detailed structured reporting of all
anatomic and molecular pathology
observations for all CAP synoptic cancer
worksheets (82 types of malignancies)
Proposal: Analyze detailed semantics of CAP
worksheets; apply harmonized concept model
to develop terminology requirements; deploy
as real-time structured reporting from
COPATH system interfaced to tissue biobank
and EPIC
Tooling: Nebraska Lexicon© extension
namespace; SNOWOWL authoring platform;
SNOMED CT International + US Extension +
Technology preview; ELK 0.4.1 DL classifier
Penciled into IHTSDO workplan for 2017
Fully Encoded Checksheet
Observables Project:
Concept model draft
SNOMED extensions for MP:
Genes and proteins
Body structures>>Cell structures>>Nucleotide
sequences and Genes
Substances>>Proteins
Qualifiers>>Techniques>> AP and MP
methods
Qualifiers>>Measurement Properties>>AP
and MP properties
Observable entity>>AP and MP observables
Clinical findings>>Anatomic and molecular
genetic observation results and disorders
Developments for MP:
Genes and proteins
Body structures>>Cell structures>>Nucleotide
sequences and Genes
Substances>>Proteins
Qualifiers>>Techniques>> AP and MP
methods
Qualifiers>>Measurement Properties>>AP
and MP properties
Observable entity>>AP and MP observables
Clinical findings>>Anatomic and molecular
genetic observation results and disorders
Define genes and related subcellular structures by
mapped reference to scientific ontologies classified
in conjunction with SNOMED CT & LOINC Observables
Developments for MP:
Genes and proteins
Body structures>>Cell structures>>Nucleotide
sequences and Genes
Substances>>Proteins
Qualifiers>>Techniques>> AP and MP
methods
Qualifiers>>Measurement Properties>>AP
and MP properties
Observable entity>>AP and MP observables
Clinical findings>>Anatomic and molecular
genetic
observation
results
and disorders
Define
proteins
and related
molecular
structures by
mapped reference to scientific ontologies classified
in conjunction with SNOMED CT & LOINC Observables
MP: Immunohistochemistry
Development for MP:
Sequence datatypes
Molecular Pathology Finding:
Fully defining observations of somatic sequence
variants
Patient Problem List:
Somatic mutation patient condition
Congenital (germline) mutations
“Familial adenomatous polyposis”
Cancer predilection syndrome found to
originate with multiple genetic etiologies:
FAP 1: heterozygous germline mutation of
the APC gene
Gardner syndrome: clinical variant of FAP 1;
includes desmoid tumors and other
hamartomas; mutation of APC gene
FAP 2: mutation of MUTYH
FAP 3: mutation of MTHL1
FAP 4: mutation of MSH3
MP: Germline mutation use case:
steps to define “Familial adenomatous polyposis 1”
MP:
Germline mutations
MP:
Germline mutations
Terminology development summary:
Colorectal and Breast Cancer
SNOMED CT
hierarchy
Observable entities
Anatomic Pathology
Concepts/Primitives
61/1
Molecular Genetic
Concepts/Primitives
32/3
Body Structures
Clinical findings
10/9
6/2
29/3
7/3
Procedures
Techniques
Property types
Scale types
Situations
Substances
Attributes
Qualifiers
TOTALS
2/1
4/4
8/8
0
1/0
0/0
2/2
2/2
88/29
0
7/7
2/2
9/9
0
11/11
3/3
0
100/41
Exemplar molecular extension
concepts
“BRAF nucleotide sequence
detected in excised
malignancy”
“BRAF gene locus”
“BRAF V600E variant identified
in excised malignancy”
“Pyrosequencing”
“Sequence property”
“Variant call format”
“BRAF human cellular protein”
Deployment of MP data
HL7 interface to tissue biobank for
indexing of tissue for research
community
ETL of data to i2b2 data warehouse
Publication of laboratory/pathology
observables ontology with NLM and
RI
Interface development and extension
to structured pathology data for EHR
HLA Histocompatibility
Gene and associated protein
HLA-A gene locus(cell structure)
– ISA Nucleotide sequence
– ISA Chromosome structure
– Part of Chromosome pair 6
– Chromosome region 6p22.1
49495002|HLA-A antigen(substance)|