The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells

Table 1

Top canonical pathways, upstream regulators, diseases and biofunctions, and networks.

(a)

Top canonical pathways
Name	value	Overlap
Hippo signaling	9.14E − 03	8.1% 7/86
Hepatic cholestasis	1.21E − 02	6.3% 10/159
PTEN signaling	1.64E − 02	6.7% 8/119
Maturity-onset diabetes of the young (MODY)	1.87E − 02	14.3% 3/21
Cyclins and cell cycle regulation	1.98E − 02	7.7% 6/78

(b)

Top upstream regulators
Upstream regulator	value of overlap
NS-398	5.54E − 05
NFκB (complex)	1.79E − 04
ACKR3	3.72E − 04
RP 73401	8.44E − 04
L-Dopa	1.22E − 03

(c)

Top diseases and biofunctions
Name	value	Number of molecules
Diseases and disorders
Cancer	2.00E − 02 to 1.20E − 06	511
Organismal injury and abnormalities	2.00E − 02 to 1.20E − 06	515
Hypersensitivity response	5.02E − 04 to 5.02E − 04	7
Dermatological diseases and conditions	1.97E − 02 to 6.53E − 04	25
Immunological disease	1.95E − 02 to 6.53E − 04	22
Physiological system development and function
Lymphoid tissue structure and development	2.12E − 02 to 7.93E − 05	56
Tissue morphology	2.12E − 02 to 7.93E − 05	107
Humoral immune response	1.37E − 02 to 1.84E − 04	28
Connective tissue development and function	2.12E − 02 to 2.67E − 04	42
Nervous system development and function	1.95E − 02 to 2.67E − 04	107

(d)

Top networks
ID	Associated network functions	Score
(1)	Nucleic acid metabolism, small molecule biochemistry, cell signaling	42
(2)	Auditory disease, cancer, cardiovascular disease	42
(3)	Carbohydrate metabolism, drug metabolism, small molecule biochemistry	37
(4)	Cellular growth and proliferation, tissue development, cellular movement	37
(5)	Embryonic development, humoral immune response, lymphoid tissue structure and development	33

This is a comprehensive list of the top canonical pathways and top upstream regulators with predicted differential regulation as well as diseases, biofunctions, and networks with the highest enrichment involving significant genes identified in our dataset based on values and other criteria set by IPA. Amongst the top canonical pathways, Hippo signaling has the highest overlap in genes from our dataset that are enriched in the pathway divided by the total number of genes enriched in the Hippo pathway, that is, 8.1% according to the current IPA database. NS-398 which is a cyclooxygenase inhibitor is amongst the top upstream regulator with a value of 5.54E − 05. The top diseases associated with citalopram treatment include cancer with 511 molecules predicted to have differential regulation, whereas the top physiological system development and function predicted to be effected includes nervous system development and function with 107 molecules identified by IPA. The top associated gene network functions include nucleic acid metabolism, small molecule biochemistry, and cell signaling with a score of 42 generated by the IPA algorithm. A score of 50 is considered as high and below 20 is low. Predicted activation.