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SEP 049 -- Higher-Order Interactions

SEP
Title Higher-Order Interactions
Authors Jake Beal (jakebeal@ieee.org)
Editor TBD
Type Data Model
SBOL Version SBOL 3.0.1
Replaces
Status Accepted
Created 8-Oct-2020
Last modified
Issue #104

Abstract

Biological interactions are often described using "higher-order" language, in which an interaction modulates another interaction. Here, we propose to allow this in SBOL by allowing Participation objects to include interactions as higher-order participants.

1. Rationale

Biological interactions are often described using "higher-order" language, in which an interaction modulates another interaction. For example, this is commonly the case in describing induction and sensor systems, e.g.:

  • "aTc inhibits the inhibition of pTet by TetR"
  • "Arabinose stimulates the stimulation of pBAD by AraC"

Preivously, it has been the case that such interactions could only be represented by explicitly representing the intermediate reactions and forms involved, such as the formation of the AraC/arabinose complex.

This is problematic in three ways:

  • Intermediate form representations may not always be available, e.g., we may know that a network should include an inhibition of inhibition, but not yet have committed to choice of whether the higher-level inhibitor will be siRNA binding mRNA or a small molecule binding protein, which are fundamentally different mechanisms of action.
  • Intermediate forms may not be desired in a representation at all. For example, one may desire to indicate that the araC gene stimulates pBAD without requiring representation of the AraC protein.
  • Mechanisms often have poorly understood or evolving mechanism models, and requiring additional detail may result in a representation that is ultimately incorrect. For example, the model of how AraC regulation actually works has evolved over time, but the higher-level representation of stimulation by arabinose is an empirical observation that has remained true.

All of these can be addressed by allowing an interaction to be a participant in another interaction, thereby allowing the higher-order interaction to be represented directly and transparently.

2. Specification

Section 6.5.4.1 defining the Participation class is expanded by replacing:

The participant property

The participant property MUST specify precisely one Feature object that plays the designated role in its parent Interaction object.

with:

The participant property

The participant property indicates a Feature object that plays the designated role in its parent Interaction object. Precisely one value MUST be specified for precisely one of participant or higherOrderParticipant.

The higherOrderParticipant property The higherOrderParticipant property indicates an Interaction object that plays the designated role in its parent Interaction object. Precisely one value MUST be specified for precisely one of participant or higherOrderParticipant.

3. Example or Use Case

Arabinose induction of pBAD can be specified with a higher-order interaction as follows:

  • Interaction: "AraC-stimulation", type: stimulation
    • Participation: AraC, role: stimulator
    • Participation: pBAD, role: stimulated
  • Interaction: "Ara-induction", type: stimulation
    • Participation: Arabinose, role: stimulator
    • Participation: "AraC-stimulation", role: stimulated

4. Backwards Compatibility

Bringing this into SBOL 3.0.1 means there are no backwards compatibility issues with SBOL 3.

If desired, in many (perhaps all) cases, a higher-order interaction can be expanded into an equivalent interaction with unknown intermediate species produced by an unknown process.

5. Discussion

TBD

6. Competing SEPs

None.

References

None.

Copyright

CC0
To the extent possible under law, SBOL developers has waived all copyright and related or neighboring rights to SEP 048. This work is published from: United States.