Table of Contents

Regulatory Pairs 3

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

Node A Node B
a(CHEBI:"5-fluorouracil") p(HGNC:HSPA1A)
p(SFAM:"NOTCH Family") complex(SCOMP:"p85/p110 PI3Kinase Complex")
bp(MESHPP:"DNA Damage") p(HGNC:RAD18)

Contradictory Statements 24

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:DAPK1) decreases, causesNoChange, association bp(GOBP:"cell migration")
p(HGNC:SPARC) increases, decreases bp(GOBP:"cell growth")
p(HGNC:E2F1) increases, causesNoChange bp(GOBP:"apoptotic process")
a(PH:placeholder) increases, decreases a(SCHEM:Oxaliplatin)
p(HGNC:KDM5B) increases, decreases, positiveCorrelation bp(GOBP:"cell growth")
p(HGNC:KAT5) increases, decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))
p(HGNC:HUWE1) increases, decreases p(HGNC:TP53)
a(CHEBI:bortezomib) increases, decreases bp(GOBP:"apoptotic process")
a(CHEMBLID:CHEMBL79140) increases, decreases a(SCHEM:"SN 38")
a(CHEBI:thapsigargin) increases, decreases bp(GOBP:"apoptotic process")
p(HGNC:KAT5) increases, decreases bp(GOBP:"cell growth")
p(HGNC:HDAC2) increases, decreases, association a(SCHEM:Doxorubicin)
a(CHEMBLID:CHEMBL77517) increases, decreases a(SCHEM:"SN 38")
a(PH:placeholder) increases, decreases p(HGNC:HDAC2)
p(HGNC:BRD8) increases, decreases bp(GOBP:"cell growth")
p(HGNC:GSN) decreases, directlyIncreases p(HGNC:PLAU)
p(HGNC:HDAC2) increases, decreases, association p(HGNC:ABCB1)
a(SCHEM:Cetuximab) decreases, causesNoChange path(MESHD:"Colorectal Neoplasms")
p(HGNC:TP53) increases, decreases r(HGNC:PTP4A3)
p(HGNC:SHH) increases, decreases complex(p(HGNC:PTCH1), p(HGNC:SMO))
p(HGNC:TRAP1) increases, decreases, association p(HGNC:BRAF)
p(MGI:Gstp1) increases, decreases bp(MESHPP:"Drug Resistance, Multiple")
p(HGNC:MDM2) increases, decreases p(HGNC:TP53)
a(CHEBI:"epidermal growth factor receptor antagonist") decreases, causesNoChange path(MESHD:"Colorectal Neoplasms")

Unstable Pairs 10

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 p(HGNC:KRAS) p(HGNC:YAP1)
Chaotic p(HGNC:HIF1A) p(HGNC:LOX)
Chaotic p(HGNC:HIF1A) p(HGNC:KRAS)
Chaotic p(HGNC:CTNNB1) p(HGNC:TCF7L2)
Chaotic p(HGNC:CASP8) p(HGNC:FAS)
Chaotic p(HGNC:HEXA, pmod(Glyco)) p(HGNC:HEXA, pmod(Glyco))
Chaotic p(HGNC:MAPK1) p(HGNC:PBK)
Dampened p(HGNC:HEXA) p(HGNC:HEXA)
Dampened p(HGNC:CTNNB1) p(HGNC:DKK3)
Dampened p(MGI:Gstp1) p(MGI:Gstp1)

Contradictory Triplets 34

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
Separate g(HGNC:KRT20) g(HGNC:CDX2) path(MESHD:"Colorectal Neoplasms")
Jens p(HGNC:HEXA, pmod(Glyco)) p(HGNC:HEXA, pmod(Glyco)) p(HGNC:HEXA, pmod(Glyco))
Jens p(HGNC:CTNNB1) p(HGNC:DKK3) r(HGNC:CCND1)
Jens bp(GOBP:"cell death") p(HGNC:DIABLO) p(HGNC:XIAP)
Jens p(HGNC:CTNNB1) p(HGNC:DKK3) r(HGNC:MYC)
Jens bp(GOBP:"cell growth") p(HGNC:HIF1A) p(HGNC:LOX)
Jens bp(GOBP:"phosphatidylinositol 3-kinase signaling") p(HGNC:HIF1A) p(HGNC:LOX)
Jens bp(MESHPP:Apoptosis) p(HGNC:BIRC5) p(HGNC:TP53)
Jens p(HGNC:CTNNB1) p(HGNC:DKK3) p(HGNC:TCF4)
Jens a(SCHEM:Oxaliplatin) bp(GOBP:"apoptotic process") p(HGNC:BCL2)
Jens complex(p(HGNC:PTCH1), p(HGNC:SHH)) complex(p(HGNC:PTCH1), p(HGNC:SMO)) p(HGNC:SMO)
Jens bp(GOBP:autophagy) p(HGNC:AKT1, pmod(Ph, Ser, 473)) p(HGNC:MTOR)
Jens a(CHEBI:paclitaxel) bp(GOBP:"cell growth") p(HGNC:BRD8)
Jens bp(MESHPP:"Drug Resistance") p(HGNC:AKT1) p(HGNC:STAT3)
Jens bp(GOBP:autophagy) p(HGNC:AKT1) p(HGNC:MTOR)
Jens a(CHEBI:oxaliplatin) a(SCHEM:Luteolin) p(HGNC:NFE2L2)
Jens complex(p(HGNC:CDH1), p(HGNC:CTNNB1)) path(SDIS:"tumor growth") p(HGNC:CTNNB1, pmod(Ph, Tyr))
Jens p(MGI:Gstp1) p(MGI:Gstp1) p(MGI:Gstp1)
Jens a(CHEBI:"serotonin uptake inhibitor") bp(GOBP:"MAPK cascade") bp(GOBP:"cell proliferation")
Jens a(CHEMBLID:CHEMBL77517) a(SCHEM:"SN 38") p(HGNC:TOP2A)
Jens p(HGNC:HEXA) p(HGNC:HEXA) p(HGNC:HEXA)
Jens bp(MESHPP:"Drug Resistance, Multiple") p(MGI:Gstp1) p(MGI:Gstp1)
Jens a(SCHEM:Oxaliplatin) a(SCHEM:Resveratrol) p(HGNC:CASP3)
Jens p(HGNC:NFE2L2) p(HGNC:PSMD4) p(HGNC:XPO1)
Jens a(SCHEM:Oxaliplatin) a(SCHEM:Resveratrol) p(HGNC:BCL2)
Jens a(CHEBI:"serotonin uptake inhibitor") bp(GOBP:"apoptotic process") p(HGNC:BCL2)
Jens path(MESHD:"Neoplasm Invasiveness") p(HGNC:GSN) p(HGNC:PLAU)
Jens a(CHEBI:piperazine) bp(GOBP:"apoptotic process") p(HGNC:BCL2)
Increase Mismatch p(HGNC:IGF1) p(HGNC:CTNNB1) path(MESHD:"Colorectal Neoplasms")
Increase Mismatch p(HGNC:IL6) bp(MESHPP:"Drug Resistance") p(HGNC:STAT3)
Increase Mismatch p(HGNC:HIF1A) bp(GOBP:"cell growth") p(HGNC:LOX)
Decrease Mismatch p(HGNC:SPDEF) path(MESHD:"Colorectal Neoplasms") p(HGNC:CTNNB1)
Decrease Mismatch a(SCHEM:Doxorubicin) p(HGNC:EGFR) bp(MESHPP:"Drug Resistance")
Decrease Mismatch g(HGNC:OVOL2) bp(GOBP:"Wnt signaling pathway") path(MESHD:"Colorectal Neoplasms")

Unstable Triplets 2

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 bp(GOBP:"phosphatidylinositol 3-kinase signaling") p(HGNC:HIF1A) p(HGNC:LOX)
Chaotic p(HGNC:NFE2L2) p(HGNC:PSMD4) p(HGNC:XPO1)

Causal Pathologies 10

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(MESHD:"Colorectal Neoplasms") increases g(HGNC:AREG)
path(MESHD:"Colorectal Neoplasms") increases g(HGNC:BTC)
path(MESHD:"Colorectal Neoplasms") increases g(HGNC:EGF)
path(MESHD:"Colorectal Neoplasms") increases g(HGNC:ERBB3)
path(MESHD:"Colorectal Neoplasms") increases g(HGNC:EREG)
path(MESHD:"Colorectal Neoplasms") increases g(HGNC:HBEGF)
path(MESHD:"Colorectal Neoplasms") decreases g(HGNC:NRG1)
path(MESHD:"Colorectal Neoplasms") decreases g(HGNC:RTN4RL2)
path(MESHD:"Gastrointestinal Neoplasms") decreases p(HGNC:MT1A)
path(MESHD:Anoxia) increases p(HGNC:KRAS, var(p.Gly12Val))

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