Modeling Properties of Biochemical Processes (Bio-ontologies 2011
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Presented at the 2011 ISMB Bio-ontologies SIG. A detour into the difficulties of representing the properties of processes in ontologies, and some steps towar
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Modeling Properties of Biochemical Processes (Bio-ontologies 2011
- 1. ISMB Bio-OntologiesSIG 2011 Processes and Properties Colin Batchelor 1Janna Hastings 2,3 Christoph Steinbeck 2 1 Royal Society of Chemistry, Cambridge, UK 1Chemoinformatics and Metabolism, European Bioinformatics Institute, UK 2 Swiss Centre for Affective Sciences, University of Geneva, Switzerland
- 2. How do we model the properties of processes?Rates of biochemical reactionsHeart rateSpeed of developmentWhat is the real effect of ‘regulation of heart rate’ (GO:0002027)We will work within the realist paradigm of the OBO community Saturday, July 16, 2011 2 Processes and Properties (Bio-ontologies 2011)
- 3. Continuants, occurrents and time Occurrentsextend in time and have temporal parts Continuants are fully present at each point in time that they exist at all, and their existence extends through time Saturday, July 16, 2011 3 Processes and Properties (Bio-ontologies 2011)
- 4. Qualities are dependent continuants I have a height throughout my lifetime My height is wholly present at each moment in time that it exists, which coincides which each moment that I exist, as my height is dependent on me Dependent entities must depend on independent entities Saturday, July 16, 2011 4 Processes and Properties (Bio-ontologies 2011)
- 5. Jones drove without a licence, without insurance, without lights after dark, under the influence of alcohol and above the speed limit. Which of these are properties of Jones, or Jones’s vehicle? Which are properties of the driving? And what about Jones’s heart rate?
- 6. Properties of processes? BFO admits no properties of processes beyond their boundaries and durations, as it does not allow second-order dependence In GFO, there are process roles which can accommodate some properties DOLCE explicitly allows for temporal qualities as properties of process Saturday, July 16, 2011 6 Processes and Properties (Bio-ontologies 2011)
- 7. Four kinds of is-a relation
- 8. Discrete vs. Continuous Saturday, July 16, 2011 8 Processes and Properties (Bio-ontologies 2011) Heterocyclic compound of a ring with sulfur and two nitrogen atoms fused to a benzene ring. Members inhibit sodium-potassium-chloride symporters and are used as diuretics. benzothiadiazine bendroflumethiazide chlorothiazide vs.
- 9. Class intersection vs. class union Class intersection involves differentiae that refer outside the definiendum. electronic spectroscopy involves probing the electronic modes of atoms and molecules ultraviolet spectroscopy uses ultraviolet light Class union involves differentiae that refer within the definiendum. red light is that which has a wavelength between 620 nm and 740 nm You can have both, at least for dependent continuants and occurrents.
- 10. What is heart rate? Heart rate allows comparison between two different heart beating processes: Process P can be more or less X than process P‘ To enable this comparison, X can be quantified (for a given temporal extent) Saturday, July 16, 2011 10 Processes and Properties (Bio-ontologies 2011)
- 11. How is heart rate different to speed? Saturday, July 16, 2011 11 Processes and Properties (Bio-ontologies 2011) How is heart rate different from speed? Different parts p, p’ of a process P can have different values X, X‘ at times t, t’
- 12. Saturday, July 16, 2011 12 Processes and Properties (Bio-ontologies 2011) heart beating is a slow heart beating normal heart beating fast heart beating instance of The policeman’s heart beating Jones’s heart beating
- 13. Specialization The is-a relation for process properties is specialization. fast heartbeat is the union of heartbeat at 120 bpm, 121 bpm, 122 bpm, 123 bpm, points in between, and so on and so forth.
- 14. What does heart rate depend on? The DOLCE approach would be to say something like: heart rate depends_onheartbeatdepends_onheart but if we follow BFO and disallow dependence chains then we get: heart ratedepends_onregularly beating heart and regularly beating heart is not a universal. Saturday, July 16, 2011 14 Processes and Properties (Bio-ontologies 2011)
- 15. What does heart rate depend on? Saturday, July 16, 2011 15 Processes and Properties (Bio-ontologies 2011) Jones’s Heart The beating process that is taking placeright as Jones notices the policeman Image credit: Patrick J. Lynch
- 16. The life of Socrates substance-depends upon Socrates because it is part of the essence of his particular life that it happened to Socrates. However, Socrates does not substance-depend upon his life because he might have had a different life. But Socrates existentially depends on his particular life, because he couldn’t have existed without one. heart rate substance_depends_onheart you might have a different heart rate heart rate existentially_depends_onheartbeat the same heart rate might come from a different heartbeat heartbeat substance_depends_onheart a given heart might have a different heartbeat E. J. Lowe, Ontological Dependence, The Stanford Encyclopedia of Philosophy image: bencrowe, some rights reserved
- 17. Classifying heart rates heartbeat at 90 bpmequivalentTo heartbeat and has_process_quality90 bpm OR heartbeat at 90 bpmis_aheartbeat heartbeat is_acyclical physiological process Saturday, July 16, 2011 17 Processes and Properties (Bio-ontologies 2011)
- 18. Conclusions There are process qualities and they are occurrents. Theyexistentially-depend on processes and substance-depend on the participants They fit into a determinable-subsumptionhierarchy Speed and acceleration, being wholly present at a single point in time, are conventional qualities. Saturday, July 16, 2011 18 Processes and Properties (Bio-ontologies 2011)
- 19. Acknowledgements Funding BBSRC, grant agreement number BB/G022747/1 within the "Bioinformatics and biological resources" fund Saturday, July 16, 2011 19 Processes and Properties (Bio-ontologies 2011)
Notas del editor
- Fairly recently, within the lifetime of the GO, they added the ‘regulates’ family of relations, including positive and negative regulation. These are relations that range over processes, but the semantics of what is meant by “regulation” here is left implicit (humans, at least biologists, understand what is meant here). First we present the background of the current realist approach to processes, the definition of qualities, and the reason why process properties are a sticky subject in realist ontology. We then provide a formal framework which allows a finer distinction than that which currently underlies the axiomatization of BFO, and thereafter working within this more expressive formal framework we provide a suggested model for process qualities.
- Processes extend in time; continuants exist through timeThe SNAP/SPAN distinctionProcesses have beginnings and ends and other temporal parts; contuants don’t. (What is the portion of me corresponding to this morning? Better: what is the portion of my life corresponding to this morning)Processes have temporal ordering; continuants do not. Does it make sense to say Fred was before Mary? Better: Fred lived before Mary. This could mean Fred’s whole life happened before Mary’s whole life, or it could mean various portions of his life took place before the equivalent portion of Mary’s life, such as early adulthood. Fred is a continuant; Fred’s driving a car is an occurrent (a process).
- Qualities are endurants. I have a height throughout my lifetime: this height is an attribute of me that changes as I grow, but the attribute itself is wholly present as long as I am. As long as I live, I have a height, and my hair has a colour. (Yes, white is a colour!)
- Jones drove along the road. How did he drive? He drove without a licence, without insurance, without lights after dark, under the influence of alcohol and above the speed limit. Naughty Jones. But how many of those properties were truly properties of his driving process, and how many of them were ―really‖ properties of something else, such as Jones himself? One test is whether the property goes away when the process finishes. In this simple case we can see that nearly everything is uncontroversially a property of one of the participants, be it Jones or his vehicle, except for perhaps the speed. But what happens when Jones sees the inevitable blue flashing light in the rear-view mirror?
- Process qualities can’t be qualities because they have a different relationship to time to normal qualities. The strict realist approach has thus far been that they don’t exist – processes simply don’t have qualities, and you’re mistaken if you think they do. There is another argument against process qualities as well: processes are themselves dependent entities, and process qualities, if they exist, would be second-order dependent entities – entities which are dependent on entities which are themselves dependent on other entities. Taking BFO, DOLCE and GFO together, BFO stands out as not explicitly providing for properties of processes beyond their boundaries and durations. GFO admits process roles, but only DOLCE explicitly identifies temporal qualities as being properties of processes, as applied by Devaraju and Kauppinen (2010) in their account of a blizzard. But all of these are quite vague. The shared framework is that processes/perdurants have proper temporal parts, are never wholly present at a given time, and are clearly distinct from continuants/endurants. Of the three, BFO deals most explicitly with ontological dependence as an organizing principle and has the fewest classes in it. But, DOLCE does not follow a realist paradigm – it is explicitly defined as an upper level ontology for linguistic and cognitive engineering – and as such it is not suitable for the OBO community, also bearing in mind that adoption of BFO is already widespread
- Johansson (2006) provides a useful structure for thinking about processes. He identifies four kinds of is_a relation, those of genus-subsumption, determinable-subsumption, specialization and specification. Most familiar to us in the bio-ontology community is genus-subsumption, which proceeds by way of class intersection. Less familiar is determinable-subsumption, which applies to certain sorts of quality. Here red, let us say, is the gerrymandered portion of colour that consists of scarlets, vermilions, crimsons and so forth.
- there is no way of smoothly moving between a benzene molecule and a water moleculeAnother way of expressing this contrast is that genus-subsumption hierarchies are discrete rather than continuous;, just as there is no way of moving smoothly between a portion of cytoplasm and an ion channel. In contrast, with a determinable-subsumption hierarchy, one can move smoothly across a colour volume, say, without encountering discontinuities. This is exactly like DOLCE‘s quality–quale distinction. A quality is a determinable and a quale is a determinate. It goes without question that we can write genus–differentia definitions for processes. The question we address is what sort of differentia is most suitable for representing the sorts of processes that biomedical scientists are interested in. One of the more recent controversies involving the use of performance-enhancing drugs in sport has involved Manchester City footballer KoloTouré. In February 2011, the player tested positive for a specified substance, subsequently found to be the banned diuretic bendroflumethiazide (CHEBI:3013), which he blamed on the use of dietary water tablets belonging to his wife. Touré admitted the offence, which contravened Regulation 3 of the Football Association Doping Regulations 2010-11 and was suspended from all footballing activities for six months [1], escaping the recommended two-year ban because the Football Association's independent regulatory commission ruled his intent was not to mask drug use, but instead to control his weight [2].
- At least on first glance, heart rate appears to be intrinsically bound up with a heart beating process. Furthermore, it allows comparison between different heart beating processes: we would like to have some sort of way of getting at the idea that person A‘s heart rate is faster than person B‘s heart rate. This is similar to person A‘s height, at least in some frameworks a determinable quality of person A, being greater than person B‘s. (1)Previous work on heart rate includes Lord and Stevens (2010) who argue for using mathematical modelling as the ontological model for this sort of scenario, which has much to recommend it from a computer programming point of view, but reasoning with combined mathematical and ontological models is not yet well developed, and thus, exposing the implications of the mathematical part of the model for standard reasoning tasks such as data integration will be difficult. Temalet al. (2009) model heart rate beneath both BFO and DOLCE and conclude that DOLCE is better since it allows heart rate to be a property of the heart beating process. In the Gene Ontology (GOC 2000), ‗regulation of heart rate‘ is a class (GO:0002027) with definition ‗Any process that modulates the frequency or rate of heart contraction.‘ and synonyms ―regulation of heart contraction rate‖, ―cardiac chronotropy‖, and ―regulation of rate of heart contraction‖, however, heart rate is only referred to in the text name as the target of the regulation, not explicitly included in the ontology as a separate entity. Lastly Nunes et al. (2007), using an approach based on DOLCE, explicitly describe the different steps in a single heartbeat but don‘t consider the heart rate itself.
- There is an important way in which heart rate differs from speed. Since Newton we have been happy with taking the limit of a speed as the length over which we evaluate the speed goes to zero, there is a minimal length of time over which we can think about a heart rate—a single cycle. The key point is that heart rate is only ever an average, in contrast to Jones driving along a residential street at 31 mph. This means that if the heart rate is a property of anything, it is a property of some proper part, specifically a proper temporal part, of the heart beating process, and different temporal parts have different heart rates. We need to modify proposition (1) to say: (2) Different parts p, p’ of a process P can have different values X, X‘ at times t, t‘. This is similar to how hair colour might be different for different spatial parts of your hair, but more complex because hair colour, like speed, is wholly defined for each (arbitrarily small) part. A more fruitful analogy is with length in geographic science. While most people are comfortable with length being a property (however defined), some lengths, famously that of the coastline of Scotland, vary with scale, getting longer the smaller the ruler you use until we reach the atomic scale and edges become difficult to identify. Similarly, Jones‘s heart rate at time t differs according to the length of time T, the precise processual part p, over which we consider it.
- We want to be able to say that the policeman’s heart beating process is slower than Jones’sBut this fastness and slowness isn’t a universal that stands by itself: it is intrinsically the fastness or slowness of heart beating that counts, and other fastnesses (such as that of painting) don’t compare
- Specialization and specification are directly relevant to our discussion of processes. Specifications of processes involve definitions in terms of the participants, so Jones‘s driving of a milkfloat, a tractor, a dodgem, a golf cart, a combine harvester, are all specifications of driving a vehicle. These can be written as class intersections in the normal way. Johansson, however, leaves specialization somewhat vague, giving as examples careful painting, careless painting, fast painting and slow painting, and pointing out that carefulness, carelessness, fastness and slowness in the context of painting derive from painting and aren‘t universals that are somehow transferable to other activities.
- If a given heart stops beating, or starts to beat irregularly, then it has not changed into a different kind of thing, it has merely changed its behavior. Hence there are two universals here: the heart and the beating process. Is there a way out that allows us to define heart rate in terms of formal relations in the sense of Smith and Grenon (2004)?
- The first thing to observe is that there are hidden dependence relations in the BFO framework. For example, every disposition depends on some underlying quality. Every process depends on some disposition. Likewise, just as the life of a frog substance-depends on the frog, so conversely the frog depends on its own life. But these dependence relations are weaker than Lowe‘s substance dependence, and are examples of Lowe‘s essential existential dependence, the case where it is part of the essence of x that x exists only if y exists. So our dependence relations at the class level, according to the pattern all x related_to some y, for heart rate are as follows: (5) heart rate substance_depends_on heart (6) heart rate existentially_depends_on heartbeat (7) heartbeat substance_depends_on heart Without all three parts of the triad (5)–(7) we cannot have a heart rate.
- What does this mean for dependence relations? We contrast DOLCE, which allows chains of (presumably) transitive dependence relations, so that qualities can have qualities and those qualities too can have qualities, with BFO, where any property y must first depend directly on some independent continuant x and second all y must depend on instances x of some universal X, as opposed to some ―defined class‖. BFO‘s approach is stronger in that it is more useful in constraining ontology developers, but is weak because it lacks a clear definition of ontological dependence. Lowe (2010) discusses ontological dependence at length and it is clear that the sort of dependence intended by BFO in the sense of ―independent continuant‖ as opposed to ―dependent continuant‖ is not unlike Lowe‘s substance dependence. Lowe defines it in terms of identity dependence: x depends for its identity upon y iff there is a function f such that it is part of the essence of x that x is f(y) and then says that x is a substance iff x is a particular and there is no particular y such that y is not identical with x and x depends for its identity upon y.
- The possibly naïve straw man that it counters is that instead of defining a 90 bpm heartbeat as (8) heartbeat that has_process_quality 90 bpmthen that BFO approach would instead say (9) heartbeat at 90 bpmis_a heartbeat In other words, the BFO approach is to use the subsumption hierarchy for heart beating processes to model attributes of processes. How do we decide between the two? (9) is simpler but it fails the basic test of proposition (1). There is nothing in the structure of (9) that enables us to say that heartbeat at 90 bpm is quantitatively different from heartbeat at 100 bpm. There is also nothing to contrast 4 these classes with other heartbeat subclasses such as feeble heartbeat or pounding heartbeat, which cannot be straightforwardly quantitatively compared. Proposition (8) achieves this since it includes ‗90 bpm‘ as a first-class entity in its own right. A further argument for process qualities comes from considering Johansson‘s (2006) kinds of is_a relation. We can see straight away that if we have heart rates as a kind of process quality then they fit into a clean determinable-subsumption hierarchy and proposition (8) becomes a sort of specification that we can handle with an OWL reasoner in the usual way. Conversely, we see that while (10) heartbeat is_a cyclical physiological process is an example of genus subsumption, any tree that contains both (9) and (10) will mix subsumption relations, since (9) is really a determinable subsumption relation where the processes stand in relation to each other as determinable and determinates.
- 5 CONCLUSIONS We have argued that upper-level ontologies should accept process qualities in order to handle things like heart rate, on the basis of its ontological dependence relations and from a consideration of Johansson‘s four kinds of is_a relation. Process qualities themselves are occurrents. They existentially-depend on the processes that they are process qualities of and substance-depend on the participants of those processes. They fit into a determinable-subsumption hierarchy. Not all things that might be considered to be process qualities, however, should be. In our view, speed and acceleration, for example, being wholly present at a single point in time, are conventional continuant qualities. In future work we will consider the rates of chemical reactions and whether they are qualities or process qualities.