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: CDK19

Gene summary for CDK19

Gene summary.

Gene information	Species	Human
	Gene symbol	CDK19
	Gene ID	23097
	Gene name	cyclin dependent kinase 19
	Gene Alias	CDC2L6
	Cytomap	6q21
	Gene Type	protein-coding
	GO ID	GO:0002237
	UniProtAcc	I6W807

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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
23097	CDK19	CCI_2	Human	Cervix	CC	1.26e-04	7.86e-01	0.5249
23097	CDK19	CCI_3	Human	Cervix	CC	2.20e-11	9.70e-01	0.516
23097	CDK19	HTA11_347_2000001011	Human	Colorectum	AD	1.89e-08	5.19e-01	-0.1954
23097	CDK19	HTA11_99999974143_84620	Human	Colorectum	MSS	3.97e-02	-2.50e-01	0.3005
23097	CDK19	A015-C-203	Human	Colorectum	FAP	1.88e-14	-2.41e-01	-0.1294
23097	CDK19	A015-C-204	Human	Colorectum	FAP	3.11e-02	-2.51e-01	-0.0228
23097	CDK19	A002-C-201	Human	Colorectum	FAP	2.14e-05	-1.09e-01	0.0324
23097	CDK19	A001-C-108	Human	Colorectum	FAP	8.54e-07	-1.60e-01	-0.0272
23097	CDK19	A002-C-205	Human	Colorectum	FAP	5.46e-12	-2.56e-01	-0.1236
23097	CDK19	A015-C-006	Human	Colorectum	FAP	1.03e-08	-3.48e-01	-0.0994
23097	CDK19	A015-C-106	Human	Colorectum	FAP	3.77e-04	-1.59e-01	-0.0511
23097	CDK19	A002-C-114	Human	Colorectum	FAP	3.73e-10	-2.99e-01	-0.1561
23097	CDK19	A015-C-104	Human	Colorectum	FAP	1.78e-15	-2.79e-01	-0.1899
23097	CDK19	A001-C-014	Human	Colorectum	FAP	3.40e-04	-1.83e-01	0.0135
23097	CDK19	A002-C-016	Human	Colorectum	FAP	6.48e-09	-1.00e-01	0.0521
23097	CDK19	A015-C-002	Human	Colorectum	FAP	1.95e-06	-3.24e-01	-0.0763
23097	CDK19	A001-C-203	Human	Colorectum	FAP	8.37e-04	-7.65e-02	-0.0481
23097	CDK19	A002-C-116	Human	Colorectum	FAP	9.55e-18	-2.21e-01	-0.0452
23097	CDK19	A014-C-008	Human	Colorectum	FAP	1.38e-07	-3.56e-01	-0.191
23097	CDK19	A018-E-020	Human	Colorectum	FAP	2.02e-08	-2.49e-01	-0.2034

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma

∗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:00321035	Cervix	CC	positive regulation of response to external stimulus	95/2311	427/18723	5.44e-09	5.03e-07	95
GO:00022379	Cervix	CC	response to molecule of bacterial origin	78/2311	363/18723	5.55e-07	2.06e-05	78
GO:00324969	Cervix	CC	response to lipopolysaccharide	74/2311	343/18723	9.15e-07	3.25e-05	74
GO:00313494	Cervix	CC	positive regulation of defense response	60/2311	278/18723	9.38e-06	2.11e-04	60
GO:00507273	Cervix	CC	regulation of inflammatory response	75/2311	386/18723	3.95e-05	6.18e-04	75
GO:00507294	Cervix	CC	positive regulation of inflammatory response	34/2311	142/18723	9.51e-05	1.25e-03	34
GO:00712228	Cervix	CC	cellular response to lipopolysaccharide	41/2311	209/18723	1.69e-03	1.29e-02	41
GO:00712168	Cervix	CC	cellular response to biotic stimulus	46/2311	246/18723	2.53e-03	1.76e-02	46
GO:00712198	Cervix	CC	cellular response to molecule of bacterial origin	42/2311	221/18723	2.79e-03	1.87e-02	42
GO:000223710	Endometrium	AEH	response to molecule of bacterial origin	65/2100	363/18723	9.00e-05	1.30e-03	65
GO:003249610	Endometrium	AEH	response to lipopolysaccharide	62/2100	343/18723	9.82e-05	1.41e-03	62
GO:00321036	Endometrium	AEH	positive regulation of response to external stimulus	68/2100	427/18723	1.82e-03	1.44e-02	68
GO:00712229	Endometrium	AEH	cellular response to lipopolysaccharide	37/2100	209/18723	3.30e-03	2.31e-02	37
GO:00712169	Endometrium	AEH	cellular response to biotic stimulus	42/2100	246/18723	3.65e-03	2.50e-02	42
GO:00712199	Endometrium	AEH	cellular response to molecule of bacterial origin	37/2100	221/18723	8.34e-03	4.56e-02	37
GO:000223714	Endometrium	EEC	response to molecule of bacterial origin	68/2168	363/18723	3.96e-05	6.64e-04	68
GO:003249614	Endometrium	EEC	response to lipopolysaccharide	65/2168	343/18723	4.04e-05	6.75e-04	65
GO:007122213	Endometrium	EEC	cellular response to lipopolysaccharide	40/2168	209/18723	9.31e-04	8.37e-03	40
GO:003210313	Endometrium	EEC	positive regulation of response to external stimulus	71/2168	427/18723	1.06e-03	9.18e-03	71
GO:007121613	Endometrium	EEC	cellular response to biotic stimulus	45/2168	246/18723	1.24e-03	1.03e-02	45

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

CDK19

SNV

Missense_Mutation

c.718N>A

p.Asp240Asn

p.D240N

Q9BWU1

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-AR-A1AI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CDK19

SNV

Missense_Mutation

c.15N>G

p.Phe5Leu

p.F5L

Q9BWU1

protein_coding

deleterious(0)

probably_damaging(0.935)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CDK19

SNV

Missense_Mutation

rs765349281

c.1290N>A

p.Ser430Arg

p.S430R

Q9BWU1

protein_coding

tolerated_low_confidence(0.2)

benign(0.282)

TCGA-BH-A1EY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDK19

SNV

Missense_Mutation

c.1032T>G

p.Asp344Glu

p.D344E

Q9BWU1

protein_coding

tolerated(0.06)

benign(0.109)

TCGA-C8-A1HJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CDK19

SNV

Missense_Mutation

rs765349281

c.1290N>A

p.Ser430Arg

p.S430R

Q9BWU1

protein_coding

tolerated_low_confidence(0.2)

benign(0.282)

TCGA-C8-A1HK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CDK19

SNV

Missense_Mutation

c.913N>C

p.Asp305His

p.D305H

Q9BWU1

protein_coding

deleterious(0.02)

probably_damaging(0.972)

TCGA-C8-A1HK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CDK19

SNV

Missense_Mutation

rs765349281

c.1290N>A

p.Ser430Arg

p.S430R

Q9BWU1

protein_coding

tolerated_low_confidence(0.2)

benign(0.282)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CDK19

SNV

Missense_Mutation

c.1282G>C

p.Asp428His

p.D428H

Q9BWU1

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-D8-A142-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamid

CDK19

SNV

Missense_Mutation

c.904N>T

p.Val302Phe

p.V302F

Q9BWU1

protein_coding

tolerated(0.15)

benign(0.179)

TCGA-E2-A152-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

CDK19

SNV

Missense_Mutation

novel

c.1235C>T

p.Ala412Val

p.A412V

Q9BWU1

protein_coding

tolerated(0.6)

benign(0.042)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
23097	CDK19	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR, TUMOR SUPPRESSOR	inhibitor	252827368	PEXIDARTINIB
23097	CDK19	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR, TUMOR SUPPRESSOR	inhibitor	CHEMBL3544942	RONICICLIB
23097	CDK19	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR, TUMOR SUPPRESSOR	inhibitor	178102513	PONATINIB
23097	CDK19	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR, TUMOR SUPPRESSOR		TOZASERTIB	TOZASERTIB
23097	CDK19	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR, TUMOR SUPPRESSOR	inhibitor	315661253
23097	CDK19	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR, TUMOR SUPPRESSOR	inhibitor	178102337	SORAFENIB
23097	CDK19	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR, TUMOR SUPPRESSOR		SNS-314	SNS-314
23097	CDK19	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR, TUMOR SUPPRESSOR	inhibitor	CHEMBL488436	AZD-5438
23097	CDK19	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR, TUMOR SUPPRESSOR	inhibitor	310264726
23097	CDK19	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR, TUMOR SUPPRESSOR		ALSTERPAULLONE	ALSTERPAULLONE

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