Background
The current BIFO spec (v0.02) defines Pathway Contribution as strictly unidirectional: P/CM -> PW. The reverse direction (PW -> G) is not a defined flow class and is correctly treated as nonpropagating in the reference implementation.
Mathematical motivation
In PPR-based scoring, bidirectional gene<->pathway edges create a feedback loop that amplifies pathways whose member genes are mechanistically interconnected. This is not purely an artifact, as it reflects the biology that pathway membership is a mutual relationship: genes define pathways and pathways define gene function context. The amplification is bounded by the PPR restart probability (alpha) and can be validated against topology-matched permutation nulls.
Proposed addition
Add a new flow class "Module Coherence" (or similar) to Section C:
| Flow |
Source → Target |
Meaning |
| Module Coherence |
PW → G |
Pathway membership context propagates back to member genes, reflecting coherent biological module identity |
With explicit admissibility conditions:
- Only valid for curated canonical pathway databases (MSigDB C2.CP, Hallmarks)
- Not valid for author-named gene expression signatures (CGP sets)
- Requires alpha damping in PPR to prevent unbounded amplification
Impact on reference implementation
Would require update to bifo_mapping.yaml to add pathway_associated_with_gene as weak_mechanistic_or_observational under Module Coherence flow class, with a --propagation-mode flag in bifo_conditioning.py.
Status
Deferred from bifo-paper-1 submission. Unidirectional result (null_z=48.7, rank 43/2130 based on degree ranks) is used in the submitted paper. Bidirectional option proposed as future work.
Background
The current BIFO spec (v0.02) defines Pathway Contribution as strictly unidirectional: P/CM -> PW. The reverse direction (PW -> G) is not a defined flow class and is correctly treated as nonpropagating in the reference implementation.
Mathematical motivation
In PPR-based scoring, bidirectional gene<->pathway edges create a feedback loop that amplifies pathways whose member genes are mechanistically interconnected. This is not purely an artifact, as it reflects the biology that pathway membership is a mutual relationship: genes define pathways and pathways define gene function context. The amplification is bounded by the PPR restart probability (alpha) and can be validated against topology-matched permutation nulls.
Proposed addition
Add a new flow class "Module Coherence" (or similar) to Section C:
With explicit admissibility conditions:
Impact on reference implementation
Would require update to bifo_mapping.yaml to add pathway_associated_with_gene as weak_mechanistic_or_observational under Module Coherence flow class, with a --propagation-mode flag in bifo_conditioning.py.
Status
Deferred from bifo-paper-1 submission. Unidirectional result (null_z=48.7, rank 43/2130 based on degree ranks) is used in the submitted paper. Bidirectional option proposed as future work.