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: TNK2

Gene summary for TNK2

Gene summary.

Gene information	Species	Human
	Gene symbol	TNK2
	Gene ID	10188
	Gene name	tyrosine kinase non receptor 2
	Gene Alias	ACK
	Cytomap	3q29
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q07912

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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
10188	TNK2	CCI_1	Human	Cervix	CC	6.20e-04	5.38e-01	0.528
10188	TNK2	CCI_3	Human	Cervix	CC	5.14e-04	4.73e-01	0.516
10188	TNK2	CCII_1	Human	Cervix	CC	1.31e-03	2.97e-01	0.3249
10188	TNK2	LZE20T	Human	Esophagus	ESCC	1.04e-02	7.92e-02	0.0662
10188	TNK2	LZE24T	Human	Esophagus	ESCC	1.29e-12	1.38e-01	0.0596
10188	TNK2	LZE21T	Human	Esophagus	ESCC	4.30e-06	3.26e-01	0.0655
10188	TNK2	P1T-E	Human	Esophagus	ESCC	1.90e-04	3.08e-01	0.0875
10188	TNK2	P2T-E	Human	Esophagus	ESCC	9.43e-19	2.42e-01	0.1177
10188	TNK2	P4T-E	Human	Esophagus	ESCC	1.46e-10	1.10e-01	0.1323
10188	TNK2	P5T-E	Human	Esophagus	ESCC	1.62e-03	5.68e-02	0.1327
10188	TNK2	P8T-E	Human	Esophagus	ESCC	4.40e-05	5.22e-02	0.0889
10188	TNK2	P9T-E	Human	Esophagus	ESCC	3.52e-08	1.81e-01	0.1131
10188	TNK2	P10T-E	Human	Esophagus	ESCC	8.42e-09	1.63e-01	0.116
10188	TNK2	P11T-E	Human	Esophagus	ESCC	9.44e-08	1.82e-01	0.1426
10188	TNK2	P12T-E	Human	Esophagus	ESCC	1.43e-06	1.12e-01	0.1122
10188	TNK2	P15T-E	Human	Esophagus	ESCC	4.54e-22	2.39e-01	0.1149
10188	TNK2	P16T-E	Human	Esophagus	ESCC	4.37e-07	7.12e-02	0.1153
10188	TNK2	P20T-E	Human	Esophagus	ESCC	5.09e-05	5.48e-02	0.1124
10188	TNK2	P21T-E	Human	Esophagus	ESCC	2.95e-04	1.50e-01	0.1617
10188	TNK2	P22T-E	Human	Esophagus	ESCC	1.74e-12	1.29e-01	0.1236

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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:00068987	Cervix	CC	receptor-mediated endocytosis	53/2311	244/18723	2.52e-05	4.29e-04	53
GO:00301008	Cervix	CC	regulation of endocytosis	47/2311	211/18723	3.65e-05	5.82e-04	47
GO:00725836	Cervix	CC	clathrin-dependent endocytosis	16/2311	47/18723	9.56e-05	1.25e-03	16
GO:00482597	Cervix	CC	regulation of receptor-mediated endocytosis	24/2311	110/18723	3.62e-03	2.31e-02	24
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:00086544	Esophagus	ESCC	phospholipid biosynthetic process	162/8552	253/18723	2.59e-09	5.73e-08	162
GO:0001890110	Esophagus	ESCC	placenta development	98/8552	144/18723	4.46e-08	8.11e-07	98
GO:003010018	Esophagus	ESCC	regulation of endocytosis	135/8552	211/18723	5.75e-08	1.02e-06	135
GO:00464744	Esophagus	ESCC	glycerophospholipid biosynthetic process	135/8552	211/18723	5.75e-08	1.02e-06	135
GO:0061458110	Esophagus	ESCC	reproductive system development	247/8552	427/18723	2.24e-07	3.42e-06	247
GO:004860818	Esophagus	ESCC	reproductive structure development	245/8552	424/18723	2.82e-07	4.14e-06	245
GO:00450175	Esophagus	ESCC	glycerolipid biosynthetic process	154/8552	252/18723	5.20e-07	6.96e-06	154
GO:00066446	Esophagus	ESCC	phospholipid metabolic process	218/8552	383/18723	5.37e-06	5.59e-05	218
GO:00097919	Esophagus	ESCC	post-embryonic development	56/8552	80/18723	9.08e-06	8.71e-05	56
GO:00066505	Esophagus	ESCC	glycerophospholipid metabolic process	174/8552	306/18723	4.92e-05	3.85e-04	174
GO:000689818	Esophagus	ESCC	receptor-mediated endocytosis	142/8552	244/18723	5.22e-05	4.05e-04	142
GO:007258314	Esophagus	ESCC	clathrin-dependent endocytosis	34/8552	47/18723	1.91e-04	1.21e-03	34
GO:00352647	Esophagus	ESCC	multicellular organism growth	80/8552	132/18723	3.84e-04	2.22e-03	80
GO:0006646	Esophagus	ESCC	phosphatidylethanolamine biosynthetic process	10/8552	10/18723	3.94e-04	2.26e-03	10
GO:00464864	Esophagus	ESCC	glycerolipid metabolic process	211/8552	392/18723	6.51e-04	3.46e-03	211

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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

TNK2

SNV

Missense_Mutation

novel

c.2996N>A

p.Ala999Asp

p.A999D

Q07912

protein_coding

deleterious_low_confidence(0.04)

probably_damaging(0.967)

TCGA-LL-A5YL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TNK2

SNV

Missense_Mutation

novel

c.2995N>A

p.Ala999Thr

p.A999T

Q07912

protein_coding

deleterious_low_confidence(0.04)

possibly_damaging(0.859)

TCGA-LL-A5YL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TNK2

insertion

Frame_Shift_Ins

novel

c.703_704insCTCTGGAAAGCCT

p.Asp235AlafsTer52

p.D235Afs*52

Q07912

protein_coding

TCGA-A8-A08J-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TNK2

deletion

Frame_Shift_Del

novel

c.402delN

p.Lys134AsnfsTer6

p.K134Nfs*6

Q07912

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

TNK2

SNV

Missense_Mutation

novel

c.1672N>A

p.Asp558Asn

p.D558N

Q07912

protein_coding

deleterious(0.01)

probably_damaging(0.984)

TCGA-C5-A8XH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TNK2

SNV

Missense_Mutation

rs559677615

c.2309N>T

p.Gln770Leu

p.Q770L

Q07912

protein_coding

tolerated_low_confidence(0.16)

benign(0.21)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

TNK2

SNV

Missense_Mutation

rs143850445

c.2824N>A

p.Glu942Lys

p.E942K

Q07912

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.994)

TCGA-EK-A2R7-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TNK2

SNV

Missense_Mutation

c.1069N>C

p.Phe357Leu

p.F357L

Q07912

protein_coding

deleterious(0.01)

probably_damaging(0.948)

TCGA-EK-A2RA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

TNK2

SNV

Missense_Mutation

rs756000040

c.749N>A

p.Arg250Gln

p.R250Q

Q07912

protein_coding

tolerated(0.98)

benign(0.006)

TCGA-HM-A3JK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TNK2

SNV

Missense_Mutation

rs748682309

c.901G>A

p.Glu301Lys

p.E301K

Q07912

protein_coding

tolerated(0.92)

benign(0.019)

TCGA-MU-A8JM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

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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
10188	TNK2	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, TYROSINE KINASE, ENZYME		CYC-116	CYC-116
10188	TNK2	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, TYROSINE KINASE, ENZYME		ILORASERTIB	ILORASERTIB
10188	TNK2	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, TYROSINE KINASE, ENZYME		AZD-1775	ADAVOSERTIB
10188	TNK2	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, TYROSINE KINASE, ENZYME		CENISERTIB	CENISERTIB
10188	TNK2	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, TYROSINE KINASE, ENZYME		PF-562271	PF-00562271
10188	TNK2	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, TYROSINE KINASE, ENZYME	inhibitor	249565873
10188	TNK2	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, TYROSINE KINASE, ENZYME		ZM-447439	CHEMBL202721
10188	TNK2	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, TYROSINE KINASE, ENZYME		DASATINIB	DASATINIB
10188	TNK2	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, TYROSINE KINASE, ENZYME		ALISERTIB	ALISERTIB
10188	TNK2	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, TYROSINE KINASE, ENZYME		RG-1530	RG-1530

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