Does Nicotine treat nicotine dependence?


Project Rephetio predicted a probability of 4.322% that Nicotine (DB00184) treats nicotine dependence (DOID:0050742). This probability represents a 10.97-fold enrichment over the background prevalence of treatment. This prediction is in the 100.0th percentile for Nicotine and the 100.0th percentile for nicotine dependence.

Most supportive network paths

Run the following query to show the 10 paths which contributed most to this prediction. Toggle AUTO-COMPLETE to OFF to only show relationships that are in these paths.

MATCH p0 = (:Compound {identifier: "DB00184"})-[:BINDS_CbG]-(:Gene {identifier: 8973})-[:BINDS_CbG]-(:Compound {identifier: "DB01273"})-[:TREATS_CtD]-(:Disease {identifier: "DOID:0050742"})
MATCH p1 = (:Compound {identifier: "DB00184"})-[:BINDS_CbG]-(:Gene {identifier: 1141})-[:BINDS_CbG]-(:Compound {identifier: "DB01273"})-[:TREATS_CtD]-(:Disease {identifier: "DOID:0050742"})
MATCH p2 = (:Compound {identifier: "DB00184"})-[:BINDS_CbG]-(:Gene {identifier: 1142})-[:ASSOCIATES_DaG]-(:Disease {identifier: "DOID:0050742"})
MATCH p3 = (:Compound {identifier: "DB00184"})-[:BINDS_CbG]-(:Gene {identifier: 8973})-[:ASSOCIATES_DaG]-(:Disease {identifier: "DOID:0050742"})
MATCH p4 = (:Compound {identifier: "DB00184"})-[:BINDS_CbG]-(:Gene {identifier: 1138})-[:ASSOCIATES_DaG]-(:Disease {identifier: "DOID:0050742"})
MATCH p5 = (:Compound {identifier: "DB00184"})-[:BINDS_CbG]-(:Gene {identifier: 57053})-[:ASSOCIATES_DaG]-(:Disease {identifier: "DOID:0050742"})
MATCH p6 = (:Compound {identifier: "DB00184"})-[:BINDS_CbG]-(:Gene {identifier: 1136})-[:BINDS_CbG]-(:Compound {identifier: "DB01273"})-[:TREATS_CtD]-(:Disease {identifier: "DOID:0050742"})
MATCH p7 = (:Compound {identifier: "DB00184"})-[:BINDS_CbG]-(:Gene {identifier: 1143})-[:ASSOCIATES_DaG]-(:Disease {identifier: "DOID:0050742"})
MATCH p8 = (:Compound {identifier: "DB00184"})-[:BINDS_CbG]-(:Gene {identifier: 1141})-[:ASSOCIATES_DaG]-(:Disease {identifier: "DOID:0050742"})
MATCH p9 = (:Compound {identifier: "DB00184"})-[:BINDS_CbG]-(:Gene {identifier: 1137})-[:BINDS_CbG]-(:Compound {identifier: "DB01273"})-[:TREATS_CtD]-(:Disease {identifier: "DOID:0050742"})
RETURN [p0, p1, p2, p3, p4, p5, p6, p7, p8, p9]

Is this a known treatment?

In PharmacotherapyDB v1.0, Nicotine is classified as a symptomatic indication for nicotine dependence. ClinicalTrials.gov contains 86 clinical trials investigating whether Nicotine treats nicotine dependence (NCT00046813, NCT00063323, NCT00067158, NCT00086385, NCT00108173, NCT00108537, NCT00115687, NCT00124683, NCT00135746, NCT00158171, NCT00186446, NCT00218140, NCT00218218, NCT00218244, NCT00218283, NCT00218296, NCT00258479, NCT00264342, NCT00289653, NCT00296647, NCT00307203, NCT00308763, NCT00365508, NCT00390923, NCT00396669, NCT00407277, NCT00429208, NCT00519766, NCT00534404, NCT00563563, NCT00618280, NCT00625131, NCT00710034, NCT00727103, NCT00749658, NCT00756275, NCT00790569, NCT00831155, NCT00888979, NCT00956943, NCT00960778, NCT00967005, NCT01001520, NCT01018394, NCT01040338, NCT01047527, NCT01050569, NCT01061528, NCT01067599, NCT01122238, NCT01184664, NCT01188967, NCT01208935, NCT01213524, NCT01292642, NCT01314001, NCT01329614, NCT01368653, NCT01395797, NCT01434342, NCT01457469, NCT01480232, NCT01522963, NCT01654107, NCT01664741, NCT01665066, NCT01735487, NCT01771627, NCT01780038, NCT01783912, NCT01842334, NCT01892813, NCT01925781, NCT01989507, NCT02004171, NCT02148445, NCT02232737, NCT02245308, NCT02250534, NCT02250664, NCT02347605, NCT02439944, NCT02511704, NCT02534454, NCT02592772, NCT02688374).

Contribution by path


Which paths provided the most support for this prediction? The following table shows the percent contribution of each path. The number of reported paths is limited to 25.

Percent of Prediction Percent of DWPC Metapath Length Verbose Path

11.60%

29.90%

CbGbCtD

3

Nicotine–binds–CHRNA6–binds–Varenicline–treats–nicotine dependence

11.60%

29.90%

CbGbCtD

3

Nicotine–binds–CHRNB2–binds–Varenicline–treats–nicotine dependence

10.30%

23.10%

CbGaD

2

Nicotine–binds–CHRNB3–associates–nicotine dependence

7.79%

17.50%

CbGaD

2

Nicotine–binds–CHRNA6–associates–nicotine dependence

6.63%

14.90%

CbGaD

2

Nicotine–binds–CHRNA5–associates–nicotine dependence

6.23%

14.00%

CbGaD

2

Nicotine–binds–CHRNA10–associates–nicotine dependence

5.55%

14.40%

CbGbCtD

3

Nicotine–binds–CHRNA3–binds–Varenicline–treats–nicotine dependence

4.48%

10.10%

CbGaD

2

Nicotine–binds–CHRNB4–associates–nicotine dependence

4.09%

9.20%

CbGaD

2

Nicotine–binds–CHRNB2–associates–nicotine dependence

3.32%

8.60%

CbGbCtD

3

Nicotine–binds–CHRNA4–binds–Varenicline–treats–nicotine dependence

3.32%

8.60%

CbGbCtD

3

Nicotine–binds–CHRNA7–binds–Varenicline–treats–nicotine dependence

3.32%

8.60%

CbGbCtD

3

Nicotine–binds–CHRFAM7A–binds–Varenicline–treats–nicotine dependence

3.10%

6.97%

CbGaD

2

Nicotine–binds–CHRNA3–associates–nicotine dependence

1.92%

4.31%

CbGaD

2

Nicotine–binds–CHRNA4–associates–nicotine dependence

0.34%

7.38%

CcSEcCtD

3

Nicotine–causes–Thyroid disorder–causes–Varenicline–treats–nicotine dependence

0.20%

4.24%

CcSEcCtD

3

Nicotine–causes–Abnormal faeces–causes–Varenicline–treats–nicotine dependence

0.13%

2.75%

CcSEcCtD

3

Nicotine–causes–Hoarseness–causes–Varenicline–treats–nicotine dependence

0.12%

2.58%

CcSEcCtD

3

Nicotine–causes–Aphthous stomatitis–causes–Varenicline–treats–nicotine dependence

0.12%

8.57%

CbGeAlD

3

Nicotine–binds–CHRNB3–expresses–midbrain–localizes–nicotine dependence

0.11%

2.40%

CcSEcCtD

3

Nicotine–causes–Throat irritation–causes–Varenicline–treats–nicotine dependence

0.11%

2.33%

CcSEcCtD

3

Nicotine–causes–Suicide–causes–Varenicline–treats–nicotine dependence

0.11%

0.99%

CbGpPWpGaD

4

Nicotine–binds–CHRNA9–participates–Highly calcium permeable postsynaptic nicotinic acetylcholine receptors–participates–CHRNB3–associates–nicotine dependence

0.10%

0.96%

CbGpPWpGaD

4

Nicotine–binds–CHRNA5–participates–Highly calcium permeable nicotinic acetylcholine receptors–participates–CHRNB3–associates–nicotine dependence

0.10%

0.96%

CbGpPWpGaD

4

Nicotine–binds–CHRNB3–participates–Highly calcium permeable nicotinic acetylcholine receptors–participates–CHRNA6–associates–nicotine dependence

0.10%

0.94%

CbGpPWpGaD

4

Nicotine–binds–CHRNA9–participates–Highly calcium permeable postsynaptic nicotinic acetylcholine receptors–participates–CHRNA6–associates–nicotine dependence

Contribution by metapath


Which types of paths provided the most support for this prediction? The following table shows the percent contribution of each metapath.

Metapath Percent of Prediction Path Count Length Verbose

CbGaD

44.52%

8

2

Compound–binds–Gene–associates–Disease

CbGbCtD

38.61%

6

3

Compound–binds–Gene–binds–Compound–treats–Disease

CbGpPWpGaD

10.81%

681

4

Compound–binds–Gene–participates–Pathway–participates–Gene–associates–Disease

CcSEcCtD

4.68%

111

3

Compound–causes–Side Effect–causes–Compound–treats–Disease

CbGeAlD

1.39%

39

3

Compound–binds–Gene–expresses–Anatomy–localizes–Disease

Contribution by source edge


The source edge of a path refers to its first edge. The following table shows the total contribution of each source edge across all paths. The number of displayed edges is limited to 25.

Source Edge Percent of Prediction Path Count Distinct Metapaths

Nicotine—binds—CHRNA6

20.68%

54

4

Nicotine—binds—CHRNB2

17.06%

60

4

Nicotine—binds—CHRNB3

11.92%

48

3

Nicotine—binds—CHRNA3

9.65%

57

4

Nicotine—binds—CHRNA5

8.35%

52

3

Nicotine—binds—CHRNA10

6.23%

1

1

Nicotine—binds—CHRNA4

6.06%

60

4

Nicotine—binds—CHRNB4

5.46%

53

3

Nicotine—binds—CHRNA7

3.80%

44

3

Nicotine—binds—CHRFAM7A

3.35%

2

2

Nicotine—binds—CHRNA9

1.06%

38

1

Nicotine—binds—CHRNA2

0.77%

53

2

Nicotine—causes—Thyroid disorder

0.34%

1

1

Nicotine—binds—CHAT

0.22%

22

2

Nicotine—causes—Abnormal faeces

0.20%

1

1

Nicotine—binds—CYP2A13

0.15%

10

1

Nicotine—causes—Hoarseness

0.13%

1

1

Nicotine—causes—Aphthous stomatitis

0.12%

1

1

Nicotine—causes—Throat irritation

0.11%

1

1

Nicotine—causes—Suicide

0.11%

1

1

Nicotine—causes—Sleep disturbance

0.10%

1

1

Nicotine—causes—Gastric ulcer

0.10%

1

1

Nicotine—causes—Completed suicide

0.10%

1

1

Nicotine—binds—MAOA

0.10%

25

2

Nicotine—causes—Toothache

0.09%

1

1

Contribution by target edge


The target edge of a path refers to its last edge. The following table shows the total contribution of each target edge across all paths. The number of displayed edges is limited to 25.

Target Edge Percent of Prediction Path Count Distinct Metapaths

nicotine dependence—treats—Varenicline

43.39%

117

2

nicotine dependence—associates—CHRNB3

12.22%

68

2

nicotine dependence—associates—CHRNA6

9.85%

72

2

nicotine dependence—associates—CHRNA5

7.89%

72

2

nicotine dependence—associates—CHRNA10

6.23%

1

1

nicotine dependence—associates—CHRNB4

6.08%

77

2

nicotine dependence—associates—CHRNB2

5.15%

80

2

nicotine dependence—associates—CHRNA3

4.39%

76

2

nicotine dependence—associates—CHRNA4

2.95%

80

2

nicotine dependence—localizes—brain

0.70%

24

1

nicotine dependence—localizes—midbrain

0.46%

8

1

nicotine dependence—associates—CYP2A7

0.37%

103

1

nicotine dependence—localizes—cardiovascular system

0.22%

7

1

nicotine dependence—associates—GABRA4

0.15%

43

1

nicotine dependence—associates—DRD2

0.06%

6

1

nicotine dependence—associates—AKR1B10

0.01%

11

1