1. NCI Thesaurus and Enterprise Vocabulary Services: Resources for Cancer Research Lawrence W. Wright Program Manager NCI Enterprise Vocabulary Services http://evs.nci.nih.gov/ May 13, 2015

2. EVS Purpose and Scope 2

3. NCI Thesaurus (NCIt): Semantic Backbone for Research Information Terminology : Provide best-practice coding as needed in all relevant domains. -Cancers and other diseases, findings and abnormalities. -Clinical & research trials/studies, procedures, tools, management, etc. -Agents, regimens, chemicals, nutrients, nanoparticles, & other substances. -Anatomy, tissues, subcellular structures. -Genes, gene products, pathways, biological processes. -Animal models – mouse, rat, zebrafish, other. -Concepts, properties, qualifiers, administrative & other misc. terminology. Ontology : Deep & precise representation of key research and health concepts. -Neoplasms 8,000+ concepts defined using 200,000 description logic relationships plus text definitions. Tracks latest molecular, pathological, and clinical classifications. -Drugs 17,000+ individual agents & related substances, including nutritional. 3,400+ agent combinations being extended to cover specific regimens. -Molecular 16,000+ genes, gene products, pathways, and abnormalities. -Anatomy 6,750+ concepts including systems, structures, tissues, and an extensive microanatomy. Federal Consolidated Health Informatics (CHI) standard. 3

4. NCIt Example: Lymphoma (1 of 5) 4 Concept Code Links to caDSR and NCIm NCI Preferred Term NCI Definition

5. NCIt Example: Lymphoma (2 of 5) 5 Term Source Tagged C3208 stakeholders (incl. Contributing_Source): CTEP, CTRP, PDQ, TCGA, NICHD, CDISC, FDA Term Code or Subsource

6. NCIt Example: Lymphoma (3 of 5) 6 Relationships 1: Parent and Child Concepts

7. NCIt Example: Lymphoma (4 of 5) 7 Relationships 2: Role Relationships & Subset Associations Role Relationships Associations

8. NCIt Example: Lymphoma (5 of 5) Activated B-Cell-Like Diffuse Large B-Cell Lymphoma 8 Preferred Name:Activated B-Cell-Like Diffuse Large B-Cell Lymphoma Code:C36081 Semantic Type:Neoplastic Process Parent Concepts:Diffuse Large B-Cell Lymphoma by Gene Expression Profile Aggressive Non-Hodgkin Lymphoma Definition: A biologic subset of diffuse large B-cell lymphomas with a unique molecular signature or expression profile. It represents approximately 30% of diffuse large B-cell lymphomas, and is characterized by the expression of CD44, PKCbeta1, Cyclin D2, BCL-2, and IRF4/MUM1 genes. Morphologically, these lymphomas are either centroblastic or immunoblastic (ratio 2:1). Patients with this type of diffuse large B-cell lymphoma are reported to have a less favorable outcome compared to those with a germinal center B-cell expression profile, with a 5-year survival rate of 35% and a median survival of 2 years. * Partial List

9. NCIt Drugs (1 of 2) 9

10. NCIt Drugs (2 of 2) 10

11. NCIt Biomarker Types with example concepts 11 Molecular/Genetic Markers  BRCA1 Gene; BRAF NP_004324.2:p.V600X (BRAF V600 Mutation); t(11;18)(q21;q21); BCR/ABL1 Fusion Protein p230, N-Telopeptide Laboratory Test Results  Estrogen Receptor Status; Methemoglobin Reductase Deficiency; CD34- Positive Neoplastic Cells Present; HMB-45-Positive Neoplastic Cells Present Histology/Pathology Findings  Positive Surgical Margin; Blast Cells Present in Peripheral Blood; Ductal Carcinoma Cell; Cervical Glandular Dysplasia; Atypical Mitotic Figures Antigens and Metabolic Markers  Ganglioside GM2; CD15; 2-Methoxyestradiol; 4-Hydroxyestrone; N(6)- Carboxymethyllysine; 8-Oxoguanine Physiological and Pathological Processes  DNA Methylation, Tumor Angiogenesis, Oxidative Stress, Lipid Peroxidation, S-Nitrosylation; Histone Acetylation

12. Partnered NCIt subsets http://ncit.nci.nih.gov/ncitbrowser/pages/subset.jsf 12

13. Partnered NCIt subsets (1 of 550): FDA SPL Drug Route of Administration Terminology 13

14. Cross Map by Meaning NCI Metathesaurus https://ncim.nci.nih.gov 14 Definitions Terms & Sources

15. NCI Hosted Mappings nciterms.nci.nih.gov/ncitbrowser/pages/mapping_search.jsf?nav_type=mappings 15

16. NCI Unified, Open Infrastructure LexEVS Server & NCI Term Browser http://nciterms.nci.nih.gov/ 16 22 Sources Search Linked Resources 3 Resource Types 25 / 75 Subsources

17. NCI Metadata in caDSR Widely Used in NCI & Partner Semantic Infrastructures 17

18. Some Lessons (1 of 2) Coding and representation of biomedical information will remain diverse and dynamic. -Many ‘legacy’ systems will be widely used for a long time to come. -Their content and use can be improved in important ways. -There is a large and growing role for more innovative resources responsive to specific research and care needs. Responsiveness and partnerships are vital: Engage to analyze and address needs quickly, form strategic partnerships and communities around key needs. Open standards encourage participation and reuse: Harmonize and share as openly and widely as possible, have expert staff to support operations. -Scale of reuse can easily exceed scale of original uses. Open technical standards and tools such as OWL/RDF, CTS2/REST, Protégé, LexEVS, and NCI browsers increase sharing and compatibility. 18

19. Some Lessons (2 of 2) Core best practices are vital: Stable codes for precise meanings, clear terms and synonymy, human-readable text definitions, extensive quality control, expert staff and community input. NCIt reference terminology provides semantic backbone for most EVS-supported coding, analyzing, and sharing research data. NCIt embedded partner terminology combines tighter semantics, harmonization, shared coding, and partner-appropriate terms. NCIm and related mappings are very useful for reference, NLP, and translation, but have weaker semantics and use. User driven priorities create relevance but also unevenness: EVS combines broad scope and rich ontology with some gaps and simple coding. 19

20. EVS Resources Web & Wiki Pages: EVS Web Portal: http://evs.nci.nih.gov/http://evs.nci.nih.gov/ EVS Wiki: https://wiki.nci.nih.gov/display/EVS/EVS+Wikihttps://wiki.nci.nih.gov/display/EVS/EVS+Wiki EVS Bibliography: https://wiki.nci.nih.gov/display/EVS/Bibliography+on+EVS+and+Its+Use https://wiki.nci.nih.gov/display/EVS/Bibliography+on+EVS+and+Its+Use EVS Use & Collaborations: https://wiki.nci.nih.gov/display/EVS/EVS+Use+and+Collaborations https://wiki.nci.nih.gov/display/EVS/EVS+Use+and+Collaborations Browsers and Term Request: NCI Term Browser: http://nciterms.nci.nih.gov/http://nciterms.nci.nih.gov/ NCI Thesaurus: http://ncit.nci.nih.gov/http://ncit.nci.nih.gov/ NCI Metathesaurus: http://ncim.nci.nih.gov/http://ncim.nci.nih.gov/ NCI EVS Term Request Page: http://ncitermform.nci.nih.gov/http://ncitermform.nci.nih.gov/ EVS/NCIt Staff email: NCIThesaurus@mail.nih.gov NCIThesaurus@mail.nih.gov 20