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: TBK1

Gene summary for TBK1

Gene summary.

Gene information	Species	Human
	Gene symbol	TBK1
	Gene ID	29110
	Gene name	TANK binding kinase 1
	Gene Alias	FTDALS4
	Cytomap	12q14.2
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q9UHD2

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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
29110	TBK1	LZE4T	Human	Esophagus	ESCC	2.07e-12	3.66e-01	0.0811
29110	TBK1	LZE5T	Human	Esophagus	ESCC	5.99e-04	2.63e-01	0.0514
29110	TBK1	LZE7T	Human	Esophagus	ESCC	8.21e-04	3.00e-01	0.0667
29110	TBK1	LZE20T	Human	Esophagus	ESCC	2.93e-03	5.40e-02	0.0662
29110	TBK1	LZE24T	Human	Esophagus	ESCC	1.45e-07	9.24e-02	0.0596
29110	TBK1	LZE21T	Human	Esophagus	ESCC	4.92e-03	1.07e-01	0.0655
29110	TBK1	LZE6T	Human	Esophagus	ESCC	2.15e-05	1.97e-01	0.0845
29110	TBK1	P1T-E	Human	Esophagus	ESCC	2.76e-06	4.11e-01	0.0875
29110	TBK1	P2T-E	Human	Esophagus	ESCC	1.38e-29	6.02e-01	0.1177
29110	TBK1	P4T-E	Human	Esophagus	ESCC	7.26e-26	1.86e-01	0.1323
29110	TBK1	P5T-E	Human	Esophagus	ESCC	1.41e-20	2.15e-01	0.1327
29110	TBK1	P8T-E	Human	Esophagus	ESCC	7.06e-29	4.74e-01	0.0889
29110	TBK1	P9T-E	Human	Esophagus	ESCC	4.78e-14	2.33e-01	0.1131
29110	TBK1	P10T-E	Human	Esophagus	ESCC	1.45e-16	2.62e-01	0.116
29110	TBK1	P11T-E	Human	Esophagus	ESCC	1.16e-08	4.39e-01	0.1426
29110	TBK1	P12T-E	Human	Esophagus	ESCC	2.32e-07	1.09e-01	0.1122
29110	TBK1	P15T-E	Human	Esophagus	ESCC	2.91e-15	3.44e-01	0.1149
29110	TBK1	P16T-E	Human	Esophagus	ESCC	8.14e-15	1.58e-01	0.1153
29110	TBK1	P17T-E	Human	Esophagus	ESCC	1.35e-03	2.59e-01	0.1278
29110	TBK1	P19T-E	Human	Esophagus	ESCC	7.45e-06	3.35e-01	0.1662

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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
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

∗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:00019594	Oral cavity	OSCC	regulation of cytokine-mediated signaling pathway	87/7305	150/18723	1.82e-06	2.35e-05	87
GO:00603384	Oral cavity	OSCC	regulation of type I interferon-mediated signaling pathway	28/7305	36/18723	2.45e-06	3.08e-05	28
GO:00607594	Oral cavity	OSCC	regulation of response to cytokine stimulus	92/7305	162/18723	3.25e-06	3.90e-05	92
GO:00450884	Oral cavity	OSCC	regulation of innate immune response	116/7305	218/18723	1.36e-05	1.37e-04	116
GO:00619127	Oral cavity	OSCC	selective autophagy	44/7305	68/18723	1.57e-05	1.57e-04	44
GO:00326083	Oral cavity	OSCC	interferon-beta production	37/7305	56/18723	3.74e-05	3.32e-04	37
GO:00326483	Oral cavity	OSCC	regulation of interferon-beta production	37/7305	56/18723	3.74e-05	3.32e-04	37
GO:00324816	Oral cavity	OSCC	positive regulation of type I interferon production	38/7305	58/18723	3.91e-05	3.43e-04	38
GO:00162393	Oral cavity	OSCC	positive regulation of macroautophagy	40/7305	63/18723	7.19e-05	5.67e-04	40
GO:00327283	Oral cavity	OSCC	positive regulation of interferon-beta production	27/7305	39/18723	1.27e-04	9.09e-04	27
GO:00321037	Oral cavity	OSCC	positive regulation of response to external stimulus	203/7305	427/18723	1.79e-04	1.22e-03	203
GO:00607604	Oral cavity	OSCC	positive regulation of response to cytokine stimulus	36/7305	57/18723	1.91e-04	1.28e-03	36
GO:00192214	Oral cavity	OSCC	cytokine-mediated signaling pathway	222/7305	472/18723	2.02e-04	1.35e-03	222
GO:00019614	Oral cavity	OSCC	positive regulation of cytokine-mediated signaling pathway	32/7305	50/18723	3.02e-04	1.89e-03	32
GO:00324793	Oral cavity	OSCC	regulation of type I interferon production	54/7305	95/18723	3.17e-04	1.97e-03	54
GO:00326063	Oral cavity	OSCC	type I interferon production	54/7305	95/18723	3.17e-04	1.97e-03	54
GO:000181910	Oral cavity	OSCC	positive regulation of cytokine production	213/7305	467/18723	1.93e-03	8.96e-03	213
GO:00022184	Oral cavity	OSCC	activation of innate immune response	31/7305	52/18723	2.08e-03	9.59e-03	31
GO:00181079	Oral cavity	OSCC	peptidyl-threonine phosphorylation	60/7305	116/18723	3.59e-03	1.50e-02	60
GO:00182109	Oral cavity	OSCC	peptidyl-threonine modification	64/7305	125/18723	3.68e-03	1.52e-02	64

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05014210	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa05022210	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa05169210	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa05170210	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa05167211	Esophagus	ESCC	Kaposi sarcoma-associated herpesvirus infection	136/4205	194/8465	4.28e-09	4.22e-08	2.16e-08	136
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0513526	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa05171211	Esophagus	ESCC	Coronavirus disease - COVID-19	156/4205	232/8465	3.18e-08	2.68e-07	1.37e-07	156
hsa0414010	Esophagus	ESCC	Autophagy - animal	101/4205	141/8465	7.60e-08	6.21e-07	3.18e-07	101
hsa05417211	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa05163210	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa051609	Esophagus	ESCC	Hepatitis C	107/4205	157/8465	1.75e-06	1.08e-05	5.55e-06	107
hsa051619	Esophagus	ESCC	Hepatitis B	108/4205	162/8465	7.68e-06	4.15e-05	2.12e-05	108
hsa04137210	Esophagus	ESCC	Mitophagy - animal	54/4205	72/8465	9.33e-06	4.96e-05	2.54e-05	54
hsa0465727	Esophagus	ESCC	IL-17 signaling pathway	66/4205	94/8465	3.93e-05	1.75e-04	8.99e-05	66
hsa051629	Esophagus	ESCC	Measles	90/4205	139/8465	2.16e-04	7.87e-04	4.03e-04	90
hsa0462122	Esophagus	ESCC	NOD-like receptor signaling pathway	116/4205	186/8465	2.90e-04	1.03e-03	5.30e-04	116
hsa046234	Esophagus	ESCC	Cytosolic DNA-sensing pathway	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49

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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

TBK1

SNV

Missense_Mutation

novel

c.1664N>A

p.Leu555Gln

p.L555Q

Q9UHD2

protein_coding

deleterious(0.01)

probably_damaging(0.995)

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

TBK1

SNV

Missense_Mutation

c.81A>T

p.Arg27Ser

p.R27S

Q9UHD2

protein_coding

deleterious(0.01)

probably_damaging(0.991)

TCGA-AN-A0FW-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TBK1

SNV

Missense_Mutation

novel

c.1136N>C

p.Ile379Thr

p.I379T

Q9UHD2

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-LL-A73Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

TBK1

insertion

Frame_Shift_Ins

novel

c.1662_1663insTT

p.Leu555PhefsTer3

p.L555Ffs*3

Q9UHD2

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

TBK1

deletion

Frame_Shift_Del

novel

c.388delN

p.Gly130ValfsTer2

p.G130Vfs*2

Q9UHD2

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

TBK1

SNV

Missense_Mutation

novel

c.77N>A

p.Gly26Glu

p.G26E

Q9UHD2

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

TBK1

SNV

Missense_Mutation

novel

c.1478N>T

p.Ala493Val

p.A493V

Q9UHD2

protein_coding

tolerated(0.3)

benign(0)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TBK1

SNV

Missense_Mutation

c.19N>T

p.His7Tyr

p.H7Y

Q9UHD2

protein_coding

tolerated(1)

benign(0)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TBK1

SNV

Missense_Mutation

c.1738N>A

p.Glu580Lys

p.E580K

Q9UHD2

protein_coding

deleterious(0.01)

probably_damaging(0.971)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TBK1

SNV

Missense_Mutation

c.177N>C

p.Leu59Phe

p.L59F

Q9UHD2

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-VS-A9UO-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
29110	TBK1	ENZYME, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME		TAMATINIB	R-406
29110	TBK1	ENZYME, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME		AZD-1775	ADAVOSERTIB
29110	TBK1	ENZYME, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME		DNDI1417467	CHEMBL1997335
29110	TBK1	ENZYME, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME		Pyrimidinyl compound 6
29110	TBK1	ENZYME, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME		Pyrimidinyl compound 7
29110	TBK1	ENZYME, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME		Pyrimidinyl compound 1
29110	TBK1	ENZYME, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME		PF-562271	PF-00562271
29110	TBK1	ENZYME, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME	inhibitor	336446964
29110	TBK1	ENZYME, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME	inhibitor	336446965
29110	TBK1	ENZYME, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME		CYC-116	CYC-116

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