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: CSNK1G1

Gene summary for CSNK1G1

Gene summary.

Gene information	Species	Human
	Gene symbol	CSNK1G1
	Gene ID	53944
	Gene name	casein kinase 1 gamma 1
	Gene Alias	CK1gamma1
	Cytomap	15q22.31
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	U3KQB3

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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
53944	CSNK1G1	LZE4T	Human	Esophagus	ESCC	9.45e-09	2.33e-01	0.0811
53944	CSNK1G1	LZE7T	Human	Esophagus	ESCC	2.11e-02	3.26e-01	0.0667
53944	CSNK1G1	LZE20T	Human	Esophagus	ESCC	4.67e-02	9.64e-02	0.0662
53944	CSNK1G1	LZE24T	Human	Esophagus	ESCC	2.41e-08	1.49e-01	0.0596
53944	CSNK1G1	P2T-E	Human	Esophagus	ESCC	8.86e-14	3.13e-01	0.1177
53944	CSNK1G1	P4T-E	Human	Esophagus	ESCC	5.57e-09	2.59e-01	0.1323
53944	CSNK1G1	P5T-E	Human	Esophagus	ESCC	4.20e-15	2.43e-01	0.1327
53944	CSNK1G1	P8T-E	Human	Esophagus	ESCC	6.22e-13	3.25e-01	0.0889
53944	CSNK1G1	P9T-E	Human	Esophagus	ESCC	4.46e-15	3.84e-01	0.1131
53944	CSNK1G1	P10T-E	Human	Esophagus	ESCC	8.45e-17	3.31e-01	0.116
53944	CSNK1G1	P11T-E	Human	Esophagus	ESCC	1.24e-11	3.19e-01	0.1426
53944	CSNK1G1	P12T-E	Human	Esophagus	ESCC	3.72e-17	4.02e-01	0.1122
53944	CSNK1G1	P15T-E	Human	Esophagus	ESCC	4.75e-22	4.65e-01	0.1149
53944	CSNK1G1	P16T-E	Human	Esophagus	ESCC	7.99e-15	2.95e-01	0.1153
53944	CSNK1G1	P20T-E	Human	Esophagus	ESCC	6.95e-12	3.17e-01	0.1124
53944	CSNK1G1	P21T-E	Human	Esophagus	ESCC	3.33e-10	2.15e-01	0.1617
53944	CSNK1G1	P22T-E	Human	Esophagus	ESCC	3.05e-18	2.08e-01	0.1236
53944	CSNK1G1	P23T-E	Human	Esophagus	ESCC	7.97e-20	4.86e-01	0.108
53944	CSNK1G1	P24T-E	Human	Esophagus	ESCC	1.56e-08	2.04e-01	0.1287
53944	CSNK1G1	P26T-E	Human	Esophagus	ESCC	1.75e-26	4.94e-01	0.1276

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia

∗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:001605517	Esophagus	ESCC	Wnt signaling pathway	268/8552	444/18723	2.32e-10	6.58e-09	268
GO:019873817	Esophagus	ESCC	cell-cell signaling by wnt	269/8552	446/18723	2.41e-10	6.79e-09	269
GO:003011117	Esophagus	ESCC	regulation of Wnt signaling pathway	194/8552	328/18723	5.39e-07	7.14e-06	194
GO:006007016	Esophagus	ESCC	canonical Wnt signaling pathway	180/8552	303/18723	9.15e-07	1.17e-05	180
GO:006082817	Esophagus	ESCC	regulation of canonical Wnt signaling pathway	153/8552	253/18723	1.38e-06	1.67e-05	153
GO:00182099	Esophagus	ESCC	peptidyl-serine modification	196/8552	338/18723	3.07e-06	3.47e-05	196
GO:001810515	Esophagus	ESCC	peptidyl-serine phosphorylation	184/8552	315/18723	3.22e-06	3.61e-05	184
GO:009026316	Esophagus	ESCC	positive regulation of canonical Wnt signaling pathway	69/8552	106/18723	4.22e-05	3.39e-04	69
GO:003017716	Esophagus	ESCC	positive regulation of Wnt signaling pathway	87/8552	140/18723	6.18e-05	4.73e-04	87
GO:019873821	Liver	HCC	cell-cell signaling by wnt	247/7958	446/18723	2.11e-08	4.96e-07	247
GO:001605521	Liver	HCC	Wnt signaling pathway	245/7958	444/18723	3.68e-08	8.09e-07	245
GO:003011121	Liver	HCC	regulation of Wnt signaling pathway	180/7958	328/18723	3.62e-06	4.72e-05	180
GO:001810511	Liver	HCC	peptidyl-serine phosphorylation	169/7958	315/18723	3.86e-05	3.81e-04	169
GO:006007021	Liver	HCC	canonical Wnt signaling pathway	162/7958	303/18723	7.00e-05	6.32e-04	162
GO:006082821	Liver	HCC	regulation of canonical Wnt signaling pathway	137/7958	253/18723	1.15e-04	9.70e-04	137
GO:001820911	Liver	HCC	peptidyl-serine modification	177/7958	338/18723	1.45e-04	1.17e-03	177
GO:003017721	Liver	HCC	positive regulation of Wnt signaling pathway	81/7958	140/18723	1.73e-04	1.36e-03	81
GO:009026321	Liver	HCC	positive regulation of canonical Wnt signaling pathway	62/7958	106/18723	6.44e-04	3.99e-03	62
GO:00160556	Lung	IAC	Wnt signaling pathway	95/2061	444/18723	1.13e-10	2.80e-08	95
GO:01987386	Lung	IAC	cell-cell signaling by wnt	95/2061	446/18723	1.46e-10	3.48e-08	95

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04340	Lung	AIS	Hedgehog signaling pathway	14/961	56/8465	3.21e-03	1.82e-02	1.17e-02	14
hsa043401	Lung	AIS	Hedgehog signaling pathway	14/961	56/8465	3.21e-03	1.82e-02	1.17e-02	14

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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

CSNK1G1

SNV

Missense_Mutation

novel

c.904N>T

p.Pro302Ser

p.P302S

Q9HCP0

protein_coding

deleterious(0.03)

possibly_damaging(0.839)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CSNK1G1

SNV

Missense_Mutation

rs779009615

c.488N>A

p.Arg163Gln

p.R163Q

Q9HCP0

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CSNK1G1

SNV

Missense_Mutation

novel

c.898N>C

p.Glu300Gln

p.E300Q

Q9HCP0

protein_coding

deleterious(0.02)

benign(0.41)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CSNK1G1

SNV

Missense_Mutation

c.1100G>A

p.Arg367Gln

p.R367Q

Q9HCP0

protein_coding

tolerated(0.11)

benign(0.246)

TCGA-G4-6306-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

CSNK1G1

SNV

Missense_Mutation

novel

c.581N>G

p.Tyr194Cys

p.Y194C

Q9HCP0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CSNK1G1

SNV

Missense_Mutation

c.508T>G

p.Phe170Val

p.F170V

Q9HCP0

protein_coding

deleterious(0.02)

probably_damaging(0.997)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CSNK1G1

SNV

Missense_Mutation

c.38G>A

p.Arg13Gln

p.R13Q

Q9HCP0

protein_coding

deleterious_low_confidence(0.03)

benign(0.145)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

CSNK1G1

SNV

Missense_Mutation

rs145663344

c.766N>A

p.Ala256Thr

p.A256T

Q9HCP0

protein_coding

deleterious(0.01)

probably_damaging(0.973)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CSNK1G1

SNV

Missense_Mutation

rs377487424

c.452G>A

p.Arg151Gln

p.R151Q

Q9HCP0

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

CSNK1G1

SNV

Missense_Mutation

c.692N>A

p.Arg231Lys

p.R231K

Q9HCP0

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

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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
53944	CSNK1G1	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	249565843
53944	CSNK1G1	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		PF-562271	PF-00562271
53944	CSNK1G1	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		CENISERTIB	CENISERTIB
53944	CSNK1G1	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		ALSTERPAULLONE	ALSTERPAULLONE
53944	CSNK1G1	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		ILORASERTIB	ILORASERTIB
53944	CSNK1G1	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		CHIR-99021	CHIR-99021
53944	CSNK1G1	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	363894217	VORUCICLIB
53944	CSNK1G1	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		CYC-116	CYC-116
53944	CSNK1G1	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		PHA-767491	CHEMBL225519
53944	CSNK1G1	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		(RS)-ROSCOVITINE	(RS)-ROSCOVITINE

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