essential elements for semi- automating biological and clinical reasoning in oncology roger s. day,...
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Essential Elements For Semi-automating Biological And
Clinical Reasoning In Oncology
Roger S. Day, William E. Shirey, Michele MorrisUniversity of Pittsburgh
Big in Modeling of Cancer
What are cancer models good for?– Discovering general principles– Professional training– Prediction for planning experiments– Description of natural history, distinguishing
mechanisms & explanations– Prediction for individualizing treatments
Educational Resource for Tumor Heterogeneity
“ERTH”• Develop a computer “playground” for thinking
broadly about cancer
• Develop wide range of learning applications
• Field test, evaluate, deploy, disseminate
Oncology Thinking Cap
“OncoTCap” software
Why is tumor heterogeneity important?
• Spatial heterogeneity metastasis
It kills people.• Genetic/epigenetic heterogeneity within tumors
survival of the fittest immortalization, motility, invasion, metastatic potential, recruitment
of blood vessel, resistance to apoptosis, resistance to therapy resistance to patient’s defenses
• Natural intuition about POPULATION DYNAMICS is poor
Tumor heterogeneityA missing link in the big picture
“Cancer GenomeAnatomy”
What happens to patients
????
Population dynamics,Toxicity,
Drug interactions,Doctor/patient,
“Society of cells”,…
INFORMATION SYNTHESIS Reductionism, then holism
OncoTCap 4/Cancer Information Genie
The software platform: “Protégé”
An expert knowledge acquisition system
protégé.stanford.edu
Frame-based KB,compliant with OKBC.
The standard “tabs”Ontology developmentForms editorInstance capture
OncoTCap 4:mission creep is a good thing
• Clinical trials bottleneck:– Accrual– Time– Expense– Far “faaar” too many hypotheses to test
• Choosing which trials to do… today:– Due diligence information gathering– by hand– Model-building and prediction – by intuition
• What if…– Information gathering is empowered– Model-building/validation/prediction is empowered
Three workflows
• Knowledge capture
• Mapping from a catalog of statement templates to computer model-driving code
• Building modeling applications like tinker toys
OncoTCap 4 “Tricorn”Knowledge capturework process
Application-buildingwork processCode-mapping
work process
Workflow #2: Coding catalog
A WT gene locus for gene gene name can mutate to MUT
with rate mutrate
Example of a statement template:
Representation in statement bundles:
The gene [gene name] has values WT/WT, WT/MUT, MUT/MUT.
The mutation rate for [gene name]
from WT/WT to WT/MUT is 2 times [mutrate]
The mutation rate for [gene name]
from WT/MUT to MUT/MUT is [mutrate]
NLP and OncoTCap?
• Plug in new tools for locating published resources (like MedMiner, EDGAR).
• Parse captured text, identify concepts, map to keyword tree.
• Provide a conduit to other Ontologies, to import portions into our Keyword tree.
• Replace user-defined Keywords with standard terms from other Ontologies.
• Suggest “interpretations”– mappings into catalog of StatementTemplates.
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