Monday, November 09, 2009


Basic Formal Ontology is increasingly being used as a tool to foster semantic interoperability of data resources in the biomedical domain, and experiments are now being initiated at the fringes of the HL7 world to examine the potential benefits of BFO over the RIM as backbone ontology framework for HL7. The RIM, familiarly, recognizes only two upper-level categories, of Act and Entity. Since diseases, drug interactions, pains, ruptures, hemorrhages, fractures, and so forth, are not Entities, the RIM categorizes all of them as Acts. BFO, in contrast, has a more resourceful set of upper-level categories, including:

  • Independent Continuants (roughly corresponding to HL7 Entity)
  • Dependent Continuant (missing from HL7)
  • Occurrents (of which HL7 Act would form a subclass, alongside those occurrents which are not Acts, such as parasomnias, involuntary muscle contractions, erosion of teeth due to persistent vomiting, and so forth)
Reasonably, the question is now being raised by some in the HL7 community, as to whether new problems would be created through the use of BFO in place of the RIM. In this connection, Cecil B. Lynch has raised an objection to the effect that, as he sees it,

BFO has shortcomings for representing medical information at the granular level. Like many philosophy based upper ontologies, it suffers from defining accidental properties when they are not. This leads to issues in maturation of organisms through development cycles such as parasites go through and leads to erroneous classifications.
Cecil agreed to formulate his concerns in relation to a concrete case, in which John, a person on rotation living in the Congo, has a blood test drawn that shows sporozoites on the smear. The challenge for BFO is then to answer the following questions:

1. How does BFO deal with the question whether John has malaria when there are sporozoites detected on his blood smear?
2. How can BFO be used to classify an immature life form as a cause of a disease when the causative agent develops internally to the organism and changes its stage of life?

Werner Ceusters and I have sought to address these challenges here (a new version, here, addresses comments made by Christos Louis and posted below). Responses from the HL7 community are welcome. At the same time we have issued to Cecil, and through him to all afficionados of the RIM, an analogous challenge:

1. How does HL7 RIM deal with the question whether John has malaria when there are sporozoites detected on his blood smear?
2. How can HL7 RIM be used to classify an immature life form as a cause of a disease when the causative agent develops internally to the organism and changes its stage of life?

Responses to this challenge can be submitted as comments to this posting, or by email to All responses will be published here.

Update November 3, 2009
From: <>
To: "Werner Ceusters" <>; "Barry Smith"
<> Cc: <>
Sent: Tuesday, November 03, 2009 3:47 PM

Thanks to you both for the explanation (and education) and to Barry's point about my "unfortunate" criticism of BFO, I am beginning to be convinced but I am not sure I understand (or am yet convinced) that BFO would handle all that I would like to communicate, or could communicate in medical notes.
I suspect that my lack of convincing is more a case of my lack of use of BFO than anything else and I resolve to try a deeper application and comparison with the information model that I would normally use to define these parameters, namely an HL7 V3 model. I do think this would be a good follow on to this exercise, i.e. an expression of this same issue in a V3 model such as the CDA for Infectious disease case reports.
This has been a very enlightening exercise for me.

Update November 16, 2009:
Response from Prof. Christos (Kitsos) Louis (IMBB-FORTH / Department of Biology, University of Crete)

Overall, I think that this is a very nice idea in order to prove that BFO is indeed a powerful tool. I really liked it. But...

1) Diagnosis of malaria is extremely easy, so why make a doctor “think” first, when the only thing he has to do is a blood smear? The only possibility of mis-diagnosis is for MDs in the North who may simply not think of the disease. Also, in the opposite case cited in the abstract, if malaria is asymptomatic for whatever reason, this usually happens only in hyperendemic areas (almost exclusively the tropics) and it is of no clinical or epidemiological importance other than on a purely academic level. If, on the other hand, the audience is specialists of medical informatics (the emphasis is on informatics, i.e. people who for whatever reason don’t “like” BFO), my guess is that after taking care of the stuff below, this could certainly have positive consequences in terms of a potential global acceptance of BFO.

2) The biology of the disease and medical/diagnostic consequences: Sporozoites, as you mention in the intro, are very “short lived” in the blood. Also, due to their very low number (malaria can be caused even by one sporozoite!), they are almost impossible to detect in the blood (see wrong sentence in second paragraph of Methods)! Thus, they play zero role in the diagnostic process (and diagnosis) of malaria, which is initiated only after the first or second bout of fever. This happens days after the infectious mosquito bite and certainly not within 30 minutes. As a matter of fact, even if one rich tourist were bitten close to a hospital/clinic one would not find a single doctor willing to do a “smear” because it would be completely useless. Thus, although indeed true, anything that lies between ID#3 and right after ID#10 is absolutely irrelevant in terms of diagnosis. Furthermore, Table 3 is not only simplified but oversimplified. Malaria (disease, disposition, whatever), unless we talk about a relapse or a medically-induced one, has to start with an infectious mosquito bite, thus somehow I feel that this should be somehow be mentioned between IDs #2 and #3. Moreover, one of the crucial aspects of malaria is the recurrence of fever attacks the first of which is the one that starts the disease from the point of view of pathology. These recurring fevers make up the crucial feature that routinely leads doctors to either diagnose it as malaria or initiate the relevant diagnostic procedures. Therefore, I think that the recurring fevers should somehow find their way to Table 3. Concluding this part, I would rewrite the whole thing “starting” from the diagnostically and clinically relevant point, which is the presence of blood-stages (several kinds, and in no way called “mature”) in the peripheral blood.

3) Other comments:
i) The existence of “surviving liver stages”, i.e. hypnozoites, can only be inferred a posteriori. This may be crucial in the definition of disease (see penultimate sentence of the Discussion). Would one talk about disease solely because there may or may not be a few hypnozoites present in a few liver cells, that may or may not ever wake up?

ii) I have a big problem with Stedman’s definitions, as these first, exclude autoimmune diseases or second, are cyclical: D3 defines, among others, a disease as being a disorder while D5 says that a disorder may result from a disease! I would therefore prefer to concentrate entirely on either CDC definitions or WHO.

iii) The title’s second part is completely misleading. There is nothing about the Plasmodium life cycle here, as only part (and only part) of the vertebrate component of the life cycle is “discussed”

iv) You state “...or have no physiological counterpart at all (e.g. inflammation).” Given that inflammation is a normal response of the human body, I have certain doubts whether this should not also be “physiological” similar to the hyperventilation stated immediately before that.

1 comment:

thomasbeale said...

I believe there is a key difference between the RIM and BFO. The BFO expresses categories of phenomena in the real world. Statements could be made that can be shown to _conform_ to this ontology (or not), a la Ceusters & Smith on the Malaria question. Here, the function of the BFO is either a) to act as a semantic validity check on statements (re)formulated using it, or b) as a generator of statements that must be true by definition.

This is not the same relationship between HL7 and its 'instances' - in the latter case the RIM is mostly acting as a representational schema for data instances, with some ontological commitments being implied. This is due to the mixture of ontological categories and informational features of the RIM.

In general I think we need to be clear about where ontologies sit in the overall information ecosystem - I believe they should mainly provide the validation function referred to above.