Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: GNG4

Gene summary for GNG4

Gene summary.

Gene information	Species	Human
	Gene symbol	GNG4
	Gene ID	2786
	Gene name	G protein subunit gamma 4
	Gene Alias	GNG4
	Cytomap	1q42.3
	Gene Type	protein-coding
	GO ID	GO:0001558
	UniProtAcc	B1APZ0

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
2786	GNG4	HTA11_7696_3000711011	Human	Colorectum	AD	7.70e-20	4.59e-01	0.0674
2786	GNG4	HTA11_99999965104_69814	Human	Colorectum	MSS	1.21e-11	4.78e-01	0.281
2786	GNG4	HTA11_99999971662_82457	Human	Colorectum	MSS	4.83e-60	1.28e+00	0.3859
2786	GNG4	HTA11_99999973899_84307	Human	Colorectum	MSS	1.87e-29	1.01e+00	0.2585
2786	GNG4	HTA11_99999974143_84620	Human	Colorectum	MSS	2.10e-20	5.07e-01	0.3005
2786	GNG4	CRC-3-11773	Human	Colorectum	CRC	4.99e-12	5.29e-01	0.2564
2786	GNG4	P2T-E	Human	Esophagus	ESCC	3.08e-07	1.74e-01	0.1177
2786	GNG4	P5T-E	Human	Esophagus	ESCC	4.49e-03	1.14e-01	0.1327
2786	GNG4	P8T-E	Human	Esophagus	ESCC	3.22e-03	1.14e-01	0.0889
2786	GNG4	P9T-E	Human	Esophagus	ESCC	3.17e-04	1.50e-01	0.1131
2786	GNG4	P10T-E	Human	Esophagus	ESCC	4.28e-43	8.13e-01	0.116
2786	GNG4	P12T-E	Human	Esophagus	ESCC	1.25e-19	4.91e-01	0.1122
2786	GNG4	P16T-E	Human	Esophagus	ESCC	4.30e-22	5.28e-01	0.1153
2786	GNG4	P17T-E	Human	Esophagus	ESCC	8.07e-08	4.30e-01	0.1278
2786	GNG4	P23T-E	Human	Esophagus	ESCC	3.26e-08	3.68e-01	0.108
2786	GNG4	P24T-E	Human	Esophagus	ESCC	1.07e-03	1.04e-01	0.1287
2786	GNG4	P37T-E	Human	Esophagus	ESCC	2.83e-05	2.27e-01	0.1371
2786	GNG4	P49T-E	Human	Esophagus	ESCC	5.57e-11	1.16e+00	0.1768
2786	GNG4	P56T-E	Human	Esophagus	ESCC	1.45e-02	3.76e-01	0.1613
2786	GNG4	P57T-E	Human	Esophagus	ESCC	4.05e-06	2.14e-01	0.0926

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:0016049	Colorectum	AD	cell growth	143/3918	482/18723	2.83e-06	8.09e-05	143
GO:0001558	Colorectum	AD	regulation of cell growth	124/3918	414/18723	7.67e-06	1.86e-04	124
GO:0045926	Colorectum	AD	negative regulation of growth	70/3918	249/18723	4.07e-03	2.83e-02	70
GO:00160492	Colorectum	MSS	cell growth	123/3467	482/18723	7.15e-05	1.21e-03	123
GO:00015582	Colorectum	MSS	regulation of cell growth	105/3467	414/18723	2.97e-04	3.90e-03	105
GO:00160494	Colorectum	CRC	cell growth	95/2078	482/18723	1.51e-08	2.75e-06	95
GO:00015584	Colorectum	CRC	regulation of cell growth	78/2078	414/18723	1.84e-06	9.11e-05	78
GO:0016049110	Esophagus	ESCC	cell growth	289/8552	482/18723	1.29e-10	3.77e-09	289
GO:000155819	Esophagus	ESCC	regulation of cell growth	248/8552	414/18723	2.97e-09	6.45e-08	248
GO:00459267	Esophagus	ESCC	negative regulation of growth	148/8552	249/18723	7.88e-06	7.73e-05	148
GO:00303085	Esophagus	ESCC	negative regulation of cell growth	108/8552	188/18723	7.46e-04	3.87e-03	108
GO:001604921	Liver	HCC	cell growth	269/7958	482/18723	1.84e-09	5.35e-08	269
GO:000155821	Liver	HCC	regulation of cell growth	228/7958	414/18723	1.34e-07	2.55e-06	228
GO:00459263	Liver	HCC	negative regulation of growth	129/7958	249/18723	1.81e-03	9.37e-03	129
GO:0030308	Liver	HCC	negative regulation of cell growth	98/7958	188/18723	4.74e-03	2.02e-02	98
GO:001604917	Oral cavity	OSCC	cell growth	268/7305	482/18723	6.55e-14	3.51e-12	268
GO:000155816	Oral cavity	OSCC	regulation of cell growth	228/7305	414/18723	1.74e-11	6.09e-10	228
GO:00459266	Oral cavity	OSCC	negative regulation of growth	135/7305	249/18723	7.29e-07	1.03e-05	135
GO:00303084	Oral cavity	OSCC	negative regulation of cell growth	101/7305	188/18723	2.85e-05	2.63e-04	101

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa047234	Colorectum	MSS	Retrograde endocannabinoid signaling	61/1875	148/8465	1.21e-07	1.93e-06	1.18e-06	61
hsa051634	Colorectum	MSS	Human cytomegalovirus infection	74/1875	225/8465	1.12e-04	1.01e-03	6.19e-04	74
hsa051704	Colorectum	MSS	Human immunodeficiency virus 1 infection	69/1875	212/8465	2.66e-04	1.98e-03	1.21e-03	69
hsa047284	Colorectum	MSS	Dopaminergic synapse	45/1875	132/8465	1.02e-03	5.94e-03	3.64e-03	45
hsa05167	Colorectum	MSS	Kaposi sarcoma-associated herpesvirus infection	60/1875	194/8465	2.59e-03	1.27e-02	7.81e-03	60
hsa04713	Colorectum	MSS	Circadian entrainment	32/1875	97/8465	8.84e-03	3.25e-02	1.99e-02	32
hsa04725	Colorectum	MSS	Cholinergic synapse	36/1875	113/8465	1.05e-02	3.69e-02	2.26e-02	36
hsa04926	Colorectum	MSS	Relaxin signaling pathway	40/1875	129/8465	1.18e-02	3.99e-02	2.44e-02	40
hsa047235	Colorectum	MSS	Retrograde endocannabinoid signaling	61/1875	148/8465	1.21e-07	1.93e-06	1.18e-06	61
hsa051635	Colorectum	MSS	Human cytomegalovirus infection	74/1875	225/8465	1.12e-04	1.01e-03	6.19e-04	74
hsa051705	Colorectum	MSS	Human immunodeficiency virus 1 infection	69/1875	212/8465	2.66e-04	1.98e-03	1.21e-03	69
hsa047285	Colorectum	MSS	Dopaminergic synapse	45/1875	132/8465	1.02e-03	5.94e-03	3.64e-03	45
hsa051671	Colorectum	MSS	Kaposi sarcoma-associated herpesvirus infection	60/1875	194/8465	2.59e-03	1.27e-02	7.81e-03	60
hsa047131	Colorectum	MSS	Circadian entrainment	32/1875	97/8465	8.84e-03	3.25e-02	1.99e-02	32
hsa047251	Colorectum	MSS	Cholinergic synapse	36/1875	113/8465	1.05e-02	3.69e-02	2.26e-02	36
hsa049261	Colorectum	MSS	Relaxin signaling pathway	40/1875	129/8465	1.18e-02	3.99e-02	2.44e-02	40
hsa04014	Colorectum	CRC	Ras signaling pathway	49/1091	236/8465	4.04e-04	4.50e-03	3.05e-03	49
hsa051638	Colorectum	CRC	Human cytomegalovirus infection	45/1091	225/8465	1.54e-03	1.17e-02	7.94e-03	45
hsa041512	Colorectum	CRC	PI3K-Akt signaling pathway	64/1091	354/8465	2.70e-03	1.77e-02	1.20e-02	64
hsa047288	Colorectum	CRC	Dopaminergic synapse	28/1091	132/8465	4.86e-03	2.66e-02	1.80e-02	28

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

GNG4

insertion

Frame_Shift_Ins

novel

c.139_140insAGACAGGGTCTCACTATGTTGCCTGGGTTAGTCTCGAACT

p.Ala47GlufsTer69

p.A47Efs*69

P50150

protein_coding

TCGA-A2-A0ER-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

GNG4

SNV

Missense_Mutation

rs756924811

c.197N>A

p.Arg66His

p.R66H

P50150

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-D5-6535-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

GNG4

SNV

Missense_Mutation

rs764998095

c.196C>T

p.Arg66Cys

p.R66C

P50150

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

GNG4

SNV

Missense_Mutation

rs777087327

c.44N>G

p.Gln15Arg

p.Q15R

P50150

protein_coding

tolerated(0.1)

probably_damaging(0.992)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

GNG4

SNV

Missense_Mutation

c.116C>T

p.Ala39Val

p.A39V

P50150

protein_coding

deleterious(0.02)

possibly_damaging(0.869)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

GNG4

SNV

Missense_Mutation

c.116C>T

p.Ala39Val

p.A39V

P50150

protein_coding

deleterious(0.02)

possibly_damaging(0.869)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

GNG4

SNV

Missense_Mutation

c.163A>G

p.Ile55Val

p.I55V

P50150

protein_coding

tolerated(0.18)

benign(0.235)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

GNG4

SNV

Missense_Mutation

rs759798253

c.210N>A

p.Phe70Leu

p.F70L

P50150

protein_coding

tolerated(1)

benign(0.009)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

GNG4

SNV

Missense_Mutation

rs769944125

c.145G>A

p.Val49Met

p.V49M

P50150

protein_coding

deleterious(0.03)

benign(0.015)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

GNG4

SNV

Missense_Mutation

rs747916965

c.148C>T

p.Arg50Trp

p.R50W

P50150

protein_coding

deleterious(0)

possibly_damaging(0.761)

TCGA-BS-A0UM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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