Pathways and Networks for Realists Barry Smith 1

Everything in biological reality exists on the level of particulars 2

A contrast Ontologies are about reality (about the types in reality – cell, membrane, protein – the particulars instantiating which we see in our labs) Data structures used in pathway and network representations are about something else (‘models’, ‘abstractions’) 3

4 What is it on the side of reality to which these data structures relate? When creating a database, we need to constrain the data structures to those which a given software system can process The need is to specify a set of valid data structures to carry information of needed sorts

5 Data structures vs. the world All persons have a sex Not all data structures about people have a field for sex Data structures are in this sense closed We can describe them completely Ontologies are intrinsically open We can never describe the world completely

6 Data structures vs. ontologies Data structures represent certain human artefacts (‘models’, ‘abstractions’) belonging to a closed (made-up) world Question: Is this right? Are pathways and networks themselves made-up entities? Or are they entities in the world, like cells and organisms?

Jeff Shrager: Fictionalism “The Fiction of Function” Bioinformatics 2003; 19(15): 1934–1936 7

Fictionalism A molecule's function is the role it plays in a story told by a biologist. The Gene Ontology is a listing of roles, and without the stories, it doesn't really make sense. Are networks and pathways like this? Do they merely reflect stories told by biologists (or bioinformaticians)? 8

Fictionalism Networks and pathways seem to be very peculiar sorts of entities compared to other denizens of the causal-energetic world of biological phenoma (cells, organs, tumors, …) Pathways and networks are highly sensitive to choice of data representation, They are, surely, abstractions, models of the scruffy reality beyond – some sort of data objects 9

Problems with fictionalism Functional genomics, and network and pathway biology, would be distinct from other parts of science (a part of literature) Yet we seem to be able to do experiments with pathways, e.g. to manipulate them (with drugs, toxins, probes …), to watch what happens, to discover new results 10

11 Simple representations can be true

12 View this with open-world spectacles

13 There are true cartoons

14 What are the true parts of this representation?

15 There are true cartoon sequences

16 What are the true parts of this representation?

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18 Pathway diagrams are annotated dynamic (= implicitly temporal) cartoons

What do these annotated dynamic cartoons (diagrams) represent? What are pathways? What are networks? 19

20 two kinds of annotations

21 names of particulars

22 names of types

23 molecular images and radiographic images are representations of particulars

ontologies are representations of types 24

but every ontology should be a representations of particulars also 25

26 pathway maps are representations of complexes of types what are the particulars here?

27 pathway maps are representations of complexes of types first enzyme, second enzyme – same type, different loci

What is being represented here on the level of particulars? Pathways and networks are fiat entities They are parts of reality which have fiat boundaries = they are demarcated from their surroundings through human cognitive acts 28

1. At external boundaries 29

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2. Selectional 31

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34 maps may be correct by reflecting topology, rather than geometry

3. Granular thresholds Pathway data doesn’t reflect all of the biology Every representation has a granular threshold 35

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The Republic of China is a fiat entity 38

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but this is nonetheless a true map of something in reality 40