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: TLK1

Gene summary for TLK1

Gene summary.

Gene information	Species	Human
	Gene symbol	TLK1
	Gene ID	9874
	Gene name	tousled like kinase 1
	Gene Alias	PKU-beta
	Cytomap	2q31.1
	Gene Type	protein-coding
	GO ID	GO:0001672
	UniProtAcc	Q9UKI8

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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
9874	TLK1	CA_HPV_1	Human	Cervix	CC	4.78e-08	1.47e-02	0.0264
9874	TLK1	CCI_2	Human	Cervix	CC	5.72e-05	7.72e-01	0.5249
9874	TLK1	CCI_3	Human	Cervix	CC	1.14e-03	7.14e-01	0.516
9874	TLK1	HTA11_3410_2000001011	Human	Colorectum	AD	8.77e-23	-6.62e-01	0.0155
9874	TLK1	HTA11_2951_2000001011	Human	Colorectum	AD	9.94e-03	-7.39e-01	0.0216
9874	TLK1	HTA11_411_2000001011	Human	Colorectum	SER	3.50e-02	3.56e-01	-0.2602
9874	TLK1	HTA11_3361_2000001011	Human	Colorectum	AD	4.11e-05	-5.73e-01	-0.1207
9874	TLK1	HTA11_696_2000001011	Human	Colorectum	AD	2.13e-03	-3.29e-01	-0.1464
9874	TLK1	HTA11_5212_2000001011	Human	Colorectum	AD	1.14e-04	-6.65e-01	-0.2061
9874	TLK1	HTA11_5216_2000001011	Human	Colorectum	SER	3.25e-02	-6.07e-01	-0.1462
9874	TLK1	HTA11_866_3004761011	Human	Colorectum	AD	9.57e-16	-6.42e-01	0.096
9874	TLK1	HTA11_9408_2000001011	Human	Colorectum	AD	5.36e-03	-8.13e-01	0.0451
9874	TLK1	HTA11_8622_2000001021	Human	Colorectum	SER	6.21e-07	-8.01e-01	0.0528
9874	TLK1	HTA11_10711_2000001011	Human	Colorectum	AD	1.50e-11	-6.35e-01	0.0338
9874	TLK1	HTA11_7696_3000711011	Human	Colorectum	AD	1.15e-15	-5.44e-01	0.0674
9874	TLK1	HTA11_6818_2000001011	Human	Colorectum	AD	7.71e-04	-6.22e-01	0.0112
9874	TLK1	HTA11_99999970781_79442	Human	Colorectum	MSS	4.06e-04	-4.12e-01	0.294
9874	TLK1	HTA11_99999971662_82457	Human	Colorectum	MSS	2.15e-13	-6.01e-01	0.3859
9874	TLK1	HTA11_99999973899_84307	Human	Colorectum	MSS	4.94e-12	-7.39e-01	0.2585
9874	TLK1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.49e-21	-6.79e-01	0.3005

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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
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
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗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:00063257	Cervix	CC	chromatin organization	78/2311	409/18723	5.40e-05	8.02e-04	78
GO:00181057	Cervix	CC	peptidyl-serine phosphorylation	63/2311	315/18723	6.65e-05	9.47e-04	63
GO:00182096	Cervix	CC	peptidyl-serine modification	66/2311	338/18723	9.58e-05	1.25e-03	66
GO:0006325	Colorectum	AD	chromatin organization	119/3918	409/18723	4.85e-05	8.33e-04	119
GO:0018105	Colorectum	AD	peptidyl-serine phosphorylation	88/3918	315/18723	1.73e-03	1.43e-02	88
GO:0018209	Colorectum	AD	peptidyl-serine modification	92/3918	338/18723	3.19e-03	2.36e-02	92
GO:00063251	Colorectum	SER	chromatin organization	89/2897	409/18723	4.15e-04	6.17e-03	89
GO:00181051	Colorectum	SER	peptidyl-serine phosphorylation	66/2897	315/18723	5.47e-03	4.06e-02	66
GO:00063252	Colorectum	MSS	chromatin organization	107/3467	409/18723	7.22e-05	1.21e-03	107
GO:00181052	Colorectum	MSS	peptidyl-serine phosphorylation	81/3467	315/18723	8.92e-04	9.12e-03	81
GO:00182091	Colorectum	MSS	peptidyl-serine modification	84/3467	338/18723	2.12e-03	1.79e-02	84
GO:00181053	Colorectum	FAP	peptidyl-serine phosphorylation	71/2622	315/18723	2.51e-05	5.82e-04	71
GO:00182092	Colorectum	FAP	peptidyl-serine modification	73/2622	338/18723	8.47e-05	1.51e-03	73
GO:00063253	Colorectum	FAP	chromatin organization	84/2622	409/18723	1.62e-04	2.47e-03	84
GO:00181054	Colorectum	CRC	peptidyl-serine phosphorylation	61/2078	315/18723	9.88e-06	3.31e-04	61
GO:00063254	Colorectum	CRC	chromatin organization	74/2078	409/18723	1.48e-05	4.61e-04	74
GO:00182093	Colorectum	CRC	peptidyl-serine modification	62/2078	338/18723	4.67e-05	1.10e-03	62
GO:000705911	Esophagus	ESCC	chromosome segregation	238/8552	346/18723	1.72e-18	1.82e-16	238
GO:000632517	Esophagus	ESCC	chromatin organization	240/8552	409/18723	6.52e-08	1.14e-06	240
GO:00182099	Esophagus	ESCC	peptidyl-serine modification	196/8552	338/18723	3.07e-06	3.47e-05	196

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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

TLK1

SNV

Missense_Mutation

c.1331C>T

p.Ser444Leu

p.S444L

Q9UKI8

protein_coding

deleterious(0.01)

possibly_damaging(0.83)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TLK1

SNV

Missense_Mutation

c.181N>A

p.Glu61Lys

p.E61K

Q9UKI8

protein_coding

deleterious_low_confidence(0)

benign(0.125)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TLK1

SNV

Missense_Mutation

novel

c.791N>C

p.Lys264Thr

p.K264T

Q9UKI8

protein_coding

deleterious(0.02)

probably_damaging(0.998)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TLK1

SNV

Missense_Mutation

c.274N>A

p.Glu92Lys

p.E92K

Q9UKI8

protein_coding

deleterious(0.02)

probably_damaging(0.995)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TLK1

SNV

Missense_Mutation

novel

c.1285A>C

p.Asn429His

p.N429H

Q9UKI8

protein_coding

deleterious(0)

possibly_damaging(0.883)

TCGA-D8-A3Z5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TLK1

SNV

Missense_Mutation

novel

c.1619A>T

p.Tyr540Phe

p.Y540F

Q9UKI8

protein_coding

tolerated(0.11)

benign(0.084)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TLK1

SNV

Missense_Mutation

c.274N>A

p.Glu92Lys

p.E92K

Q9UKI8

protein_coding

deleterious(0.02)

probably_damaging(0.995)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TLK1

SNV

Missense_Mutation

c.817A>C

p.Met273Leu

p.M273L

Q9UKI8

protein_coding

tolerated(0.15)

probably_damaging(0.925)

TCGA-EA-A411-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TLK1

SNV

Missense_Mutation

c.2191N>T

p.Asp731Tyr

p.D731Y

Q9UKI8

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EK-A2RJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TLK1

SNV

Missense_Mutation

novel

c.1009G>A

p.Glu337Lys

p.E337K

Q9UKI8

protein_coding

tolerated(0.07)

probably_damaging(0.995)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

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

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