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Table of Contents

Regulatory Pairs 4

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

Node A Node B
p(HGNC:DKK3) p(HGNC:CTNNB1)
p(SFAM:"NOTCH Family") complex(SCOMP:"p85/p110 PI3Kinase Complex")
a(CHEBI:"5-fluorouracil") p(HGNC:HSPA1A)
bp(MESHPP:"DNA Damage") p(HGNC:RAD18)

Contradictory Statements 41

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
a(CHEBI:bortezomib) increases, decreases bp(MESHPP:Apoptosis)
a(MeSH:panitumumab) decreases, causesNoChange path(MESHD:"Colorectal Neoplasms")
m(HGNC:MIR497) increases, decreases bp(MESHPP:"Drug Resistance")
p(MGI:Gstp1) increases, decreases bp(MESHPP:"Drug Resistance, Multiple")
a(PH:placeholder) increases, decreases a(CHEBI:oxaliplatin)
p(HGNC:TP53) increases, decreases r(HGNC:PTP4A3)
complex(p(HGNC:EGFR), p(HGNC:ITGB1)) increases, causesNoChange bp(MESHPP:"Absorption, Radiation")
p(HGNC:SLC29A1) increases, decreases a(CHEBI:"5-fluorouracil")
a(MESHC:"Antibodies, Monoclonal") decreases, causesNoChange path(MESHD:"Colorectal Neoplasms")
p(HGNC:HDAC2) increases, decreases, association p(HGNC:ABCB1)
p(HGNC:SPARC) increases, decreases bp(GOBP:"cell growth")
a(CHEBI:"SN-38") increases, decreases p(HGNC:TOP1)
bp(MESHPP:Fasting) decreases, causesNoChange a(CHEBI:irinotecan)
p(HGNC:HUWE1) increases, decreases p(HGNC:TP53)
p(HGNC:HGF) increases, decreases, biomarkerFor bp(MESHPP:"Drug Resistance")
composite(a(CHEBI:oxaliplatin), a(MeSH:Cetuximab)) decreases, causesNoChange path(MESHD:"Colorectal Neoplasms")
p(HGNC:KDM5B) increases, decreases, positiveCorrelation bp(GOBP:"cell growth")
a(CHEBI:thapsigargin) increases, decreases bp(MESHPP:Apoptosis)
p(HGNC:DAPK1) decreases, causesNoChange, association bp(GOBP:"cell migration")
p(HGNC:MDM2) increases, decreases p(HGNC:TP53)
p(HGNC:BRAF) increases, decreases p(HGNC:TGFBRAP1, pmod(Ph, Ser))
a(MeSH:Cetuximab) increases, causesNoChange bp(MeSH:"Survival Rate")
composite(a(CHEBI:"5-fluorouracil"), a(CHEBI:capecitabine)) increases, causesNoChange bp(MeSH:Mortality)
p(HGNC:HDAC2) increases, decreases, association a(CHEBI:doxorubicin)
p(HGNC:GSN) decreases, directlyIncreases p(HGNC:PLAU)
p(HGNC:DKK3) increases, decreases, negativeCorrelation p(HGNC:CTNNB1)
p(HGNC:E2F1) increases, causesNoChange bp(MESHPP:Apoptosis)
p(HGNC:KAT5) increases, decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))
a(MeSH:Cetuximab) increases, decreases p(HGNC:MAPK14)
a(CHEBI:"5-fluorouracil") increases, decreases, association bp(MESHPP:"Drug Resistance")
a(CHEBI:sulindac) increases, decreases bp(GOBP:"cell growth")
p(HGNC:TRAP1) increases, decreases, association p(HGNC:BRAF)
a(MeSH:Cetuximab) decreases, causesNoChange path(MESHD:"Colorectal Neoplasms")
p(HGNC:BRD8) increases, decreases bp(GOBP:"cell growth")
m(HGNC:MIR497) increases, decreases, association a(CHEBI:"5-fluorouracil")
a(CHEMBLID:CHEMBL77517) increases, decreases a(CHEBI:"SN-38")
p(HGNC:MYC) increases, decreases r(HGNC:CDKN1B)
p(HGNC:KAT5) increases, decreases bp(GOBP:"cell growth")
p(HGNC:RAD18) increases, decreases bp(MESHPP:"DNA Damage")
p(HGNC:SHH) increases, decreases complex(p(HGNC:PTCH1), p(HGNC:SMO))
a(CHEBI:"epidermal growth factor receptor antagonist") decreases, causesNoChange path(MESHD:"Colorectal Neoplasms")

Unstable Pairs 14

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:MAPK1) p(HGNC:PBK)
Chaotic p(HGNC:CASP8) p(HGNC:FAS)
Chaotic p(HGNC:HEXA, pmod(Glyco)) p(HGNC:HEXA, pmod(Glyco))
Chaotic p(HGNC:CTNNB1) p(HGNC:TCF7L2)
Chaotic p(HGNC:KRAS) p(HGNC:YAP1)
Chaotic p(HGNC:HIF1A) p(HGNC:KRAS)
Chaotic a(MeSH:"trifluridine tipiracil") a(MeSH:"trifluridine tipiracil")
Chaotic bp(MESHPP:"DNA Damage") p(HGNC:RAD18)
Chaotic p(HGNC:HIF1A) p(HGNC:LOX)
Chaotic a(MeSH:"2-amino-8-(4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido(2,3-d)pyrimidin-7(8H)-one") p(HGNC:EGFR)
Dampened p(HGNC:CTNNB1) p(HGNC:DKK3)
Dampened p(MGI:Gstp1) p(MGI:Gstp1)
Dampened p(HGNC:HEXA) p(HGNC:HEXA)
Dampened m(HGNC:MIR27B) m(HGNC:MIR27B)

Contradictory Triplets 61

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 a(CHEBI:"SN-38") a(CHEMBLID:CHEMBL77517) p(HGNC:TOP2A)
Jens a(CHEBI:irinotecan) path(MESHD:"Colorectal Neoplasms") p(HGNC:UBE3D)
Jens path(MESHD:"Neoplasm Invasiveness") p(HGNC:GSN) p(HGNC:PLAU)
Jens a(CHEBI:"5-fluorouracil") bp(MESHPP:"Drug Resistance") p(HGNC:IL24)
Jens p(HGNC:CTNNB1) p(HGNC:DKK3) r(HGNC:MYC)
Jens a(MeSH:Cetuximab) bp(GOBP:"cell proliferation") p(HGNC:ERBB2)
Jens p(HGNC:HEXA, pmod(Glyco)) p(HGNC:HEXA, pmod(Glyco)) p(HGNC:HEXA, pmod(Glyco))
Jens bp(MESHPP:Apoptosis) p(HGNC:BIRC5) p(HGNC:TP53)
Jens a(CHEBI:"5-fluorouracil") bp(MESHPP:"Drug Resistance") m(HGNC:MIR497)
Jens a(CHEBI:luteolin) a(CHEBI:oxaliplatin) p(HGNC:NFE2L2)
Jens a(CHEBI:irinotecan) bp(GOBP:"cell growth") p(HGNC:UBE3D)
Jens a(CHEBI:"serotonin uptake inhibitor") bp(MESHPP:Apoptosis) p(HGNC:BCL2)
Jens p(HGNC:CTNNB1) p(HGNC:DKK3) r(HGNC:CCND1)
Jens a(CHEBI:paclitaxel) bp(GOBP:"cell growth") p(HGNC:BRD8)
Jens bp(GOBP:"cell death") p(HGNC:DIABLO) p(HGNC:XIAP)
Jens a(CHEBI:"5-fluorouracil") bp(MESHPP:"Drug Resistance") p(HGNC:SMURF1)
Jens a(CHEBI:oxaliplatin) a(CHEBI:resveratrol) p(HGNC:BCL2)
Jens complex(p(HGNC:CDH1), p(HGNC:CTNNB1)) path(SDIS:"tumor growth") p(HGNC:CTNNB1, pmod(Ph, Tyr))
Jens p(HGNC:NFE2L2) p(HGNC:PSMD4) p(HGNC:XPO1)
Jens a(CHEBI:"5-fluorouracil") bp(MESHPP:"Drug Resistance") p(HGNC:IL6)
Jens a(CHEBI:luteolin) a(CHEBI:oxaliplatin) p(HGNC:NQO1)
Jens bp(GOBP:autophagy) p(HGNC:AKT1, pmod(Ph, Ser, 473)) p(HGNC:MTOR)
Jens a(CHEBI:oxaliplatin) bp(MESHPP:Apoptosis) p(HGNC:BCL2)
Jens a(CHEBI:"serotonin uptake inhibitor") bp(GOBP:"MAPK cascade") bp(GOBP:"cell proliferation")
Jens a(MeSH:"2-amino-8-(4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido(2,3-d)pyrimidin-7(8H)-one") p(HGNC:EGFR) p(HGNC:FOXO3)
Jens bp(MESHPP:"Drug Resistance") p(HGNC:ATM) m(HGNC:MIR203A)
Jens a(CHEBI:oxaliplatin) a(CHEBI:resveratrol) p(HGNC:CASP3)
Jens a(CHEBI:irinotecan) path(MESHD:"Colorectal Neoplasms") p(HGNC:HGF)
Jens a(CHEBI:"5-fluorouracil") bp(MESHPP:"Drug Resistance") p(HGNC:SPARC)
Jens bp(MESHPP:"Drug Resistance") p(HGNC:BIRC5) p(HGNC:STAT3)
Jens a(CHEBI:"5-fluorouracil") bp(GOBP:"cell growth") m(HGNC:MIR497)
Jens bp(MESHPP:"Drug Resistance") p(HGNC:AKT1) p(HGNC:STAT3)
Jens complex(p(HGNC:PTCH1), p(HGNC:SHH)) complex(p(HGNC:PTCH1), p(HGNC:SMO)) p(HGNC:SMO)
Jens a(MeSH:"trifluridine tipiracil") a(MeSH:"trifluridine tipiracil") a(MeSH:"trifluridine tipiracil")
Jens m(HGNC:MIR27B) m(HGNC:MIR27B) m(HGNC:MIR27B)
Jens bp(GOBP:"cell growth") p(HGNC:HIF1A) p(HGNC:LOX)
Jens p(HGNC:CTNNB1) p(HGNC:DKK3) p(HGNC:TCF4)
Jens p(MGI:Gstp1) p(MGI:Gstp1) p(MGI:Gstp1)
Jens bp(GOBP:autophagy) p(HGNC:AKT1) p(HGNC:MTOR)
Jens bp(MESHPP:"Drug Resistance, Multiple") p(MGI:Gstp1) p(MGI:Gstp1)
Jens a(MeSH:Cetuximab) path(MESHD:"Colorectal Neoplasms") p(HGNC:UBE3D)
Jens bp(GOBP:"phosphatidylinositol 3-kinase signaling") p(HGNC:HIF1A) p(HGNC:LOX)
Jens a(CHEBI:"SN-38") bp(GOBP:"cell growth") p(HGNC:UBE3D)
Jens a(CHEBI:"5-fluorouracil") p(HGNC:SMURF1) m(HGNC:MIR497)
Jens bp(MESHPP:"DNA Damage") p(HGNC:RAD18) m(HGNC:MIR145)
Jens a(CHEBI:piperazine) bp(MESHPP:Apoptosis) p(HGNC:BCL2)
Jens p(HGNC:HEXA) p(HGNC:HEXA) p(HGNC:HEXA)
Jens a(CHEBI:"5-fluorouracil") a(MESHC:"Plant Extracts") bp(MESHPP:"Drug Resistance")
Increase Mismatch p(HGNC:IL6) bp(MESHPP:"Drug Resistance") p(HGNC:STAT3)
Increase Mismatch p(HGNC:CTNNB1) path(MESHD:"Colorectal Neoplasms") bp(GOBP:"Wnt signaling pathway")
Increase Mismatch p(HGNC:HIF1A) bp(GOBP:"cell growth") p(HGNC:LOX)
Increase Mismatch p(HGNC:MET) p(HGNC:STAT3) bp(MESHPP:"Drug Resistance")
Increase Mismatch p(HGNC:IGF1) p(HGNC:CTNNB1) path(MESHD:"Colorectal Neoplasms")
Decrease Mismatch m(HGNC:MIR27B) m(HGNC:MIR27B) path(MESHD:"Colorectal Neoplasms")
Decrease Mismatch a(CHEBI:"acetylsalicylic acid") p(HGNC:CTNNB1) path(MESHD:"Colorectal Neoplasms")
Decrease Mismatch a(CHEBI:doxorubicin) p(HGNC:EGFR) bp(MESHPP:"Drug Resistance")
Decrease Mismatch p(HGNC:SPDEF) p(HGNC:CTNNB1) path(MESHD:"Colorectal Neoplasms")
Decrease Mismatch m(HGNC:MIR451A) bp(MESHPP:"Drug Resistance") p(HGNC:ABCB1)
Decrease Mismatch g(HGNC:OVOL2) bp(GOBP:"Wnt signaling pathway") path(MESHD:"Colorectal Neoplasms")
Decrease Mismatch a(MeSH:"Zuo-Jin-Wan") bp(MESHPP:"Drug Resistance") p(HGNC:ABCB1)

Unstable Triplets 3

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 a(MeSH:"2-amino-8-(4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido(2,3-d)pyrimidin-7(8H)-one") p(HGNC:EGFR) p(HGNC:FOXO3)
Chaotic p(HGNC:NFE2L2) p(HGNC:PSMD4) p(HGNC:XPO1)

Causal Pathologies 19

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:"Breast Neoplasms") decreases p(HGNC:SOX7)
path(MESHD:"Colorectal Neoplasms") increases a(GOCC:"extracellular matrix component")
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:"Colorectal Neoplasms") decreases p(HGNC:SOX7)
path(MESHD:"Esophageal Neoplasms") increases p(HGNC:SOX7)
path(MESHD:"Gastrointestinal Neoplasms") decreases p(HGNC:MT1A)
path(MESHD:"Kidney Neoplasms") decreases p(HGNC:SOX7)
path(MESHD:"Lung Neoplasms") decreases p(HGNC:SOX7)
path(MESHD:"Pancreatic Neoplasms") increases p(HGNC:SOX7)
path(MESHD:"Prostatic Neoplasms") decreases p(HGNC:SOX7)
path(MESHD:"Stomach Neoplasms") increases p(HGNC:SOX7)
path(MESHD:Hypoxia) increases p(HGNC:KRAS, var(p.Gly12Val))

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