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: TNIK

Gene summary for TNIK

Gene summary.

Gene information	Species	Human
	Gene symbol	TNIK
	Gene ID	23043
	Gene name	TRAF2 and NCK interacting kinase
	Gene Alias	MRT54
	Cytomap	3q26.2-q26.31
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q9UKE5

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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
23043	TNIK	HTA11_3410_2000001011	Human	Colorectum	AD	4.71e-10	-4.18e-01	0.0155
23043	TNIK	HTA11_347_2000001011	Human	Colorectum	AD	5.54e-06	5.49e-01	-0.1954
23043	TNIK	HTA11_866_3004761011	Human	Colorectum	AD	4.30e-07	-5.18e-01	0.096
23043	TNIK	HTA11_4255_2000001011	Human	Colorectum	SER	2.89e-02	-5.16e-01	0.0446
23043	TNIK	HTA11_10711_2000001011	Human	Colorectum	AD	5.40e-05	-5.25e-01	0.0338
23043	TNIK	HTA11_99999973899_84307	Human	Colorectum	MSS	7.03e-08	-7.20e-01	0.2585
23043	TNIK	HTA11_99999974143_84620	Human	Colorectum	MSS	1.94e-18	-6.80e-01	0.3005
23043	TNIK	A015-C-203	Human	Colorectum	FAP	8.21e-28	-5.74e-01	-0.1294
23043	TNIK	A015-C-204	Human	Colorectum	FAP	1.15e-05	-3.16e-01	-0.0228
23043	TNIK	A014-C-040	Human	Colorectum	FAP	8.87e-11	-8.53e-01	-0.1184
23043	TNIK	A002-C-201	Human	Colorectum	FAP	1.01e-14	-4.99e-01	0.0324
23043	TNIK	A001-C-119	Human	Colorectum	FAP	8.54e-15	-7.73e-01	-0.1557
23043	TNIK	A001-C-108	Human	Colorectum	FAP	1.42e-13	-3.74e-01	-0.0272
23043	TNIK	A002-C-021	Human	Colorectum	FAP	2.75e-02	-2.41e-01	0.1171
23043	TNIK	A002-C-205	Human	Colorectum	FAP	2.55e-28	-6.85e-01	-0.1236
23043	TNIK	A001-C-104	Human	Colorectum	FAP	4.56e-02	-2.62e-01	0.0184
23043	TNIK	A015-C-005	Human	Colorectum	FAP	5.16e-05	-4.31e-01	-0.0336
23043	TNIK	A015-C-006	Human	Colorectum	FAP	1.06e-28	-9.00e-01	-0.0994
23043	TNIK	A015-C-106	Human	Colorectum	FAP	2.71e-16	-4.28e-01	-0.0511
23043	TNIK	A002-C-114	Human	Colorectum	FAP	5.31e-23	-6.45e-01	-0.1561

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:01987381	Colorectum	SER	cell-cell signaling by wnt	97/2897	446/18723	2.39e-04	4.11e-03	97
GO:00163581	Colorectum	SER	dendrite development	58/2897	243/18723	3.82e-04	5.81e-03	58
GO:00315321	Colorectum	SER	actin cytoskeleton reorganization	30/2897	107/18723	6.38e-04	8.64e-03	30
GO:00109751	Colorectum	SER	regulation of neuron projection development	92/2897	445/18723	1.85e-03	1.89e-02	92
GO:0048813	Colorectum	SER	dendrite morphogenesis	36/2897	146/18723	2.51e-03	2.33e-02	36
GO:0050773	Colorectum	SER	regulation of dendrite development	27/2897	103/18723	3.35e-03	2.86e-02	27
GO:00310981	Colorectum	SER	stress-activated protein kinase signaling cascade	54/2897	247/18723	4.65e-03	3.67e-02	54
GO:00514031	Colorectum	SER	stress-activated MAPK cascade	52/2897	239/18723	5.96e-03	4.35e-02	52
GO:00726592	Colorectum	MSS	protein localization to plasma membrane	113/3467	284/18723	3.23e-17	1.55e-14	113
GO:19907782	Colorectum	MSS	protein localization to cell periphery	120/3467	333/18723	2.02e-14	5.47e-12	120
GO:00160552	Colorectum	MSS	Wnt signaling pathway	124/3467	444/18723	6.06e-07	2.26e-05	124
GO:01987382	Colorectum	MSS	cell-cell signaling by wnt	124/3467	446/18723	7.83e-07	2.77e-05	124
GO:00315322	Colorectum	MSS	actin cytoskeleton reorganization	41/3467	107/18723	1.21e-06	4.06e-05	41
GO:00109752	Colorectum	MSS	regulation of neuron projection development	115/3467	445/18723	6.91e-05	1.20e-03	115
GO:00325282	Colorectum	MSS	microvillus organization	13/3467	24/18723	9.44e-05	1.49e-03	13
GO:00467772	Colorectum	MSS	protein autophosphorylation	63/3467	227/18723	3.96e-04	4.91e-03	63
GO:00310982	Colorectum	MSS	stress-activated protein kinase signaling cascade	67/3467	247/18723	5.28e-04	5.99e-03	67
GO:00514032	Colorectum	MSS	stress-activated MAPK cascade	65/3467	239/18723	5.87e-04	6.49e-03	65
GO:00300332	Colorectum	MSS	microvillus assembly	9/3467	16/18723	8.20e-04	8.59e-03	9
GO:00163582	Colorectum	MSS	dendrite development	65/3467	243/18723	9.41e-04	9.50e-03	65

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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

TNIK

SNV

Missense_Mutation

novel

c.664N>C

p.Thr222Pro

p.T222P

Q9UKE5

protein_coding

deleterious(0.01)

probably_damaging(0.993)

TCGA-A2-A04Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TNIK

SNV

Missense_Mutation

novel

c.1642N>C

p.Ser548Pro

p.S548P

Q9UKE5

protein_coding

deleterious(0.01)

probably_damaging(0.979)

TCGA-A2-A0D0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TNIK

SNV

Missense_Mutation

c.335N>G

p.Ser112Cys

p.S112C

Q9UKE5

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNIK

SNV

Missense_Mutation

c.1679N>T

p.Ser560Phe

p.S560F

Q9UKE5

protein_coding

deleterious_low_confidence(0.03)

possibly_damaging(0.887)

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TNIK

SNV

Missense_Mutation

novel

c.1642N>C

p.Ser548Pro

p.S548P

Q9UKE5

protein_coding

deleterious(0.01)

probably_damaging(0.979)

TCGA-AR-A255-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

TNIK

SNV

Missense_Mutation

novel

c.1201N>G

p.Gln401Glu

p.Q401E

Q9UKE5

protein_coding

tolerated(0.22)

possibly_damaging(0.68)

TCGA-AR-A256-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TNIK

SNV

Missense_Mutation

rs867347961

c.3086N>G

p.Asn1029Ser

p.N1029S

Q9UKE5

protein_coding

tolerated(0.08)

benign(0.325)

TCGA-AR-A2LN-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

letrozole

TNIK

SNV

Missense_Mutation

novel

c.664A>C

p.Thr222Pro

p.T222P

Q9UKE5

protein_coding

deleterious(0.01)

probably_damaging(0.993)

TCGA-B6-A0I5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TNIK

SNV

Missense_Mutation

c.1763N>C

p.Val588Ala

p.V588A

Q9UKE5

protein_coding

deleterious(0.04)

benign(0.074)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNIK

SNV

Missense_Mutation

c.1714N>C

p.Ser572Arg

p.S572R

Q9UKE5

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.791)

TCGA-C8-A1HN-01

Breast

breast invasive carcinoma

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
23043	TNIK	ENZYME, DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE		SB-202190	SB-202190	22951114
23043	TNIK	ENZYME, DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE	inhibitor	HESPERADIN	HESPERADIN	19035792
23043	TNIK	ENZYME, DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE	inhibitor	135652717	STAUROSPORINE
23043	TNIK	ENZYME, DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE	inhibitor	249565872
23043	TNIK	ENZYME, DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE		CEP-1347	CEP-1347	24044867

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