Staging Disease with PROTEGE 4:
Example of Multiple Myeloma
Eric BRILLETa,1, Valérie BERTAUD GOUNOTa, Olivier DECAUX b,
Régis DUVAUFERRIERa, Jérémy LASBLEIZa
a
Unité Inserm U936, IFR 140IFR 140, Faculté de Médecine,
University of Rennes 1, France
b
Department of Internal Medicine CHU of Rennes, France
Abstract. The goal of this study is to create an applicative ontology of the
Multiple myeloma. We have extracted a multiple myeloma sub-ontology from the
NCI Thesaurus. Secondly, using Protégé 4 owl2, we have added the missing
classes and quantitative data properties to the ontology to improve the multiple
myeloma representation. The obtained ontology has been checked by a reasoner
(Fact++) and tested on twenty real medical reports. The twenty patients were
classified at the correct stages according to the report findings.
Keywords. NCI Thesaurus, OWL, Biomedical ontologies, Ontology, Myeloma.
1. Introduction
The goal of this study is to create an ontology of the myeloma with quantitative data
properties to obtain an applicative ontology that will permit to stage patients. To obtain
a multiple myeloma representation, we have automatically extracted from the NCI
Thesaurus [1] a sub-ontology of 281 class, 17 relations and 25 restrictions. The
extractor retrieved all ancestors up to the top, all children down to the leaves, all target
concepts connected by a restriction to PLASMA_CELL_NEOPLASM or its children.
To improve the sub-ontology, we have used Protégé [2] a free open source ontology
editor and knowledgebase Framework. The language we uses is owl2, because it can
deal with quantitative data properties, not taken into account in NCIT owl1.
In 2003, the International Myeloma Working Group have established criteria for
the diagnosis of plasma cell proliferative disorders [3]. They have distinguished
monoclonal gammopathy of undetermined significance (MGUS), which is a
premalignant disease and is defined by an intact immunoglobulin < 3 g/100 ml, < 10%
bone marrow plasma cells and absence of end-organ damage. End-organ damage
includes hypercalcemia, renal failure, anemia and bone lesions that are related to a
plasma cell proliferative disorder and not explained by another unrelated disease or
disorder. Symptomatic MM is differentiated from MGUS and Smoldering MM based
on the presence or absence of end-organ damage attributable to the underlying plasma
cell proliferative process.
Those quantitative concepts missing in the sub-ontology and needed to stage
patients, have been added with U936- as prefix in the ontology. For examples:
1
Corresponding Author


Disease stages: U936_Symptomatic_Myeloma ; U936_Durie/Salmon_Plus
Biological examination: U936_IgA_serum_Measurement
U936_Urinary_Lambda_Or_Kappa_Measurement
 Findings: U936Focal_Myeloma_Lesions_in_FDG-PET_scan
To translate definition from literal into formal, we have used new relations as
U936_Has_Value and U936_Has_Unit. Those relations are essential to describe
quantitative data properties.
2. Results
We have used a OWL reasoner, Fact++ that check consistency of the ontology in terms
of formal definitions of classes. They can classify an instance when the instance
contains all the necessary and sufficient conditions. 20 patients, with different variants
or stages of myeloma, records or exit letters have been analyzed. Each patient has been
added as a class in the ontology to allow the reasoner to work. All patients have been
reaffected into myeloma different stages.
Figure 1 Patient classified after the run of Fact++.
3. Conclusion
The ontology we built is one of the first to deal with quantitative data properties. It
permits to classify “real life patients”, with for example biological findings. Physicians,
at patient bedside, can use this tool to stage disease and take therapeutic decisions.
References
[1]
[2]
[3]
Fragoso G, de Coronado S, Haber M, Hartel F, Wright L. Overview and utilization of the NCI
thesaurus, Comp Func Genomics 5(8) (2004), 648–54.
http://protege.stanford.edu access January 2011
The international Myeloma Working group. Criteria for the classification of monoclonal gammopathies,
multiple myeloma and related disorders: a report of the international Myeloma Working group. Br J
Haematology 2003; 121: 749-57