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Biogrammar Summary of Nicotinic acetylcholine receptor signalling: roles in Alzheimer's disease and amyloid neuroprotection. 1.0.0

Table of Contents

  1. Regulatory Pairs
  2. Contradictory Pairs
  3. Unstable Pairs
  4. Contradictory Triplets
  5. Unstable Triplets
  6. Causal Pathologies

Regulatory Pairs 2

These pairs of nodes represent motifs like A increases B and B decreases A.

Node A Node B
p(HGNC:CHRNA7) a(CHEBI:"amyloid-beta")
a(CHEBI:"amyloid-beta") p(HGNC:CHRNA7)

Contradictory Statements 5

These pairs of nodes have a contradiction in their causal relationships, meaning they have more than one of INCREASES, DECREASES, or CAUSES NO CHANGE. This may be due to different experimental conditions, so these statements need to be carefully considered in analyses.

Source Relations Target
path(MESH:"Alzheimer Disease") association, decreases, increases p(HGNC:CHRNA7)
a(CHEBI:"amyloid-beta") decreases, increases complex(p(HGNC:CHRNA4), p(HGNC:CHRNB2))
p(HGNC:CHRNA7) association, decreases, positiveCorrelation, increases a(CHEBI:"amyloid-beta")
path(MESH:"Alzheimer Disease") association, decreases, increases p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")
a(CHEBI:"amyloid-beta") increases, association, positiveCorrelation, decreases, causesNoChange p(HGNC:CHRNA7)

Unstable Pairs 5

Chaotic Pairs
Nodes that mutually increase each other, such as when both A increases B and B increases A.
Dampened Pairs
Nodes that mutually decrease each other, such as when both A decreases B and B decreases A.

While neither chaotic nor dampened pairs are biologically invalid, they require additional context to understand their regulation.

Type Node A Node B
Chaotic a(CHEBI:nicotine) p(HGNC:CHRNA7)
Chaotic a(CHEBI:"amyloid-beta") p(HGNC:CHRNA7)
Chaotic a(CHEBI:nicotine) p(FPLX:PI3K)
Dampened complex(a(CHEBI:"amyloid-beta"), p(HGNC:CHRNA7)) complex(a(MESH:Bungarotoxins), p(HGNC:CHRNA7))
Dampened a(CHEBI:"amyloid-beta") p(HGNC:CHRNA7)

Contradictory Triplets 20

Analysis of triple stability comes from a deep graph theoretic background. It identifies triangles within the graph that have logically inconsistent relations.

Separately Unstable Triplet
When both A positiveCorrelation B, B negativeCorrelation C, but C positiveCorrelation A.
Mutually Unstable Triplets
When both A negativeCorrelation B, B negativeCorrelation C, and C negativeCorrelation A.
Jens Contradictory Triplet
When A increases B, A decreases C, and C positiveCorrelation A.
Increase Mismatch Triplet
When A increases B, A increases C, and C negativeCorrelation A.
Decrease Mismatch Triplet
When A decreases B, A decreases C, and C negativeCorrelation A.
Type Node A Node B Node C
Jens a(CHEBI:"amyloid-beta") p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits") path(MESH:"Alzheimer Disease")
Jens bp(GO:cognition) p(HGNC:FYN) path(MESH:"Alzheimer Disease")
Jens a(CHEBI:nicotine) p(FPLX:PI3K) p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")
Jens a(CHEBI:"amyloid-beta") p(HGNC:MAPT, pmod(Ph)) p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")
Jens a(CHEBI:"amyloid-beta") a(CHEBI:nicotine) p(HGNC:CHRNA7)
Jens a(CHEBI:"amyloid-beta") a(CHEBI:nicotine) p(HGNC:BAX)
Jens a(CHEBI:"amyloid-beta") a(CHEBI:nicotine) bp(GO:"apoptotic process")
Jens a(CHEBI:nicotine) p(HGNC:CHRNA7) p(HGNC:JAK2)
Jens a(CHEBI:"amyloid-beta") bp(GO:"MAPK cascade") p(HGNC:CHRNA7)
Jens a(CHEBI:donepezil) p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits") path(MESH:"Alzheimer Disease")
Jens a(CHEBI:donepezil) p(HGNC:CHRNA7) path(MESH:"Alzheimer Disease")
Jens a(CHEBI:donepezil) p(HGNC:CHRNA4) path(MESH:"Alzheimer Disease")
Jens a(CHEBI:"amyloid-beta") a(CHEBI:nicotine) p(FPLX:PI3K)
Jens a(CHEBI:"amyloid-beta") p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits") path(HBP:neurotoxicity)
Jens a(CHEBI:nicotine) bp(GO:"ERK1 and ERK2 cascade") bp(GO:"apoptotic process")
Jens a(CHEBI:galanthamine) p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits") path(MESH:"Alzheimer Disease")
Jens a(CHEBI:"amyloid-beta") a(CHEBI:nicotine) p(HGNC:CHRNA4)
Jens a(CHEBI:"amyloid-beta") p(HGNC:CHRNA7) path(MESH:"Alzheimer Disease")
Jens a(CHEBI:"amyloid-beta") a(CHEBI:nicotine) path(HBP:neurotoxicity)
Jens a(CHEBI:"amyloid-beta") a(MESH:Synapses) p(FPLX:PI3K)

Unstable Triplets 4

Like unstable pairs, unstable triplets require additional context to understand their mechanisms of regulation.

Chaotic Triplets
A triplet of nodes that mutually increase each other, such as when A increases B, B increases C, and C increases A.
Dampened Triplets
A triplet of nodes that mutually decreases each other, such as when A decreases B, B decreases C, and C decreases A.
Type Node A Node B Node C
Chaotic a(CHEBI:nicotine) p(FPLX:PI3K) p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")
Chaotic a(CHEBI:"amyloid-beta") p(HGNC:CHRNA7) path(MESH:"Alzheimer Disease")
Chaotic a(CHEBI:"amyloid-beta") bp(GO:"MAPK cascade") p(HGNC:CHRNA7)
Chaotic a(CHEBI:nicotine) p(HGNC:CHRNA7) p(HGNC:JAK2)

Causal Pathologies 18

Pathologies are more dogmatically the result of molecular and physical processes, and do not necessarily make sense as the subject of causal statements.

Source Relation Target
path(MESH:"Alzheimer Disease") decreases a(CHEBI:acetylcholine)
path(MESH:"Alzheimer Disease") decreases a(MESH:"Cholinergic Neurons")
path(MESH:"Alzheimer Disease") decreases a(MESH:"Cholinesterase Inhibitors")
path(MESH:"Alzheimer Disease") decreases complex(p(HGNC:CHRNA4), p(HGNC:CHRNB2))
path(MESH:"Alzheimer Disease") increases complex(p(HGNC:FYN), p(HGNC:MAPT))
path(MESH:"Alzheimer Disease") increases p(HGNC:BCHE)
path(MESH:"Alzheimer Disease") decreases p(HGNC:CHAT)
path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA3)
path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA4)
path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA7)
path(MESH:"Alzheimer Disease") increases p(HGNC:CHRNA7)
path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNB4)
path(MESH:"Alzheimer Disease") increases p(HGNC:FYN)
path(MESH:"Alzheimer Disease") decreases p(HGNC:GABRB3)
path(MESH:"Alzheimer Disease") decreases p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")
path(MESH:"Alzheimer Disease") increases p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")
path(MESH:"Alzheimer Disease") decreases p(HGNCGENEFAMILY:"Glutamate ionotropic receptor AMPA type subunits")
path(MESH:"Alzheimer Disease") decreases p(HGNCGENEFAMILY:"Glutamate ionotropic receptor NMDA type subunits")

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.