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Biogrammar Summary of The Ubiquitin Proteasome System in Neurodegenerative Diseases: Sometimes the Chicken, Sometimes the Egg 1.0.0

Table of Contents

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

Regulatory Pairs 1

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

Node A Node B
complex(GO:"proteasome complex") a(CHEBI:"amyloid-beta")

Contradictory Statements 1

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
p(HGNC:PRKN, var("?")) decreases, increases p(HGNC:PRKN)

Unstable Pairs 3

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(MESH:"Neurofibrillary Tangles") p(HGNC:MAPT)
Chaotic p(HGNC:PRNP) p(HGNC:PRNP)
Dampened a(HBP:"protein aggregates") bp(GO:"proteasome-mediated ubiquitin-dependent protein catabolic process")

Contradictory Triplets 3

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 p(HGNC:PRNP) p(HGNC:PRNP) p(HGNC:PRNP)
Jens bp(GO:"cell death") p(HGNC:RNF19A) p(HGNC:SOD1, var("?"))
Jens complex(a(GO:"proteasome complex"), p(HGNC:PRKN)) p(HGNC:PRKN, var("p.Arg42")) path(MESH:"Parkinsonian Disorders")

Causal Pathologies 5

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") increases a(MESH:"Neurofibrillary Tangles")
path(MESH:"Amyotrophic Lateral Sclerosis") decreases a(MESH:"Brain Stem")
path(MESH:"Amyotrophic Lateral Sclerosis") decreases a(MESH:"Pyramidal Tracts")
path(MESH:"Amyotrophic Lateral Sclerosis") increases p(HGNC:RNF19A)
path(MESH:"Prion Diseases") increases a(HBP:"amyloid-beta aggregates")

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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.