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: TAB2

Gene summary for TAB2

Gene summary.

Gene information	Species	Human
	Gene symbol	TAB2
	Gene ID	23118
	Gene name	TGF-beta activated kinase 1 (MAP3K7) binding protein 2
	Gene Alias	CHTD2
	Cytomap	6q25.1
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q9NYJ8

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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
23118	TAB2	HTA11_3410_2000001011	Human	Colorectum	AD	5.68e-06	-3.68e-01	0.0155
23118	TAB2	HTA11_866_3004761011	Human	Colorectum	AD	4.64e-02	-3.62e-01	0.096
23118	TAB2	HTA11_7696_3000711011	Human	Colorectum	AD	2.75e-05	-3.34e-01	0.0674
23118	TAB2	A001-C-207	Human	Colorectum	FAP	1.97e-03	-3.98e-01	0.1278
23118	TAB2	A015-C-203	Human	Colorectum	FAP	5.56e-23	-4.62e-01	-0.1294
23118	TAB2	A015-C-204	Human	Colorectum	FAP	1.40e-04	-3.70e-01	-0.0228
23118	TAB2	A002-C-201	Human	Colorectum	FAP	8.76e-13	-4.63e-01	0.0324
23118	TAB2	A002-C-203	Human	Colorectum	FAP	1.21e-09	-3.63e-01	0.2786
23118	TAB2	A001-C-119	Human	Colorectum	FAP	3.12e-05	-4.21e-01	-0.1557
23118	TAB2	A001-C-108	Human	Colorectum	FAP	8.86e-20	-4.67e-01	-0.0272
23118	TAB2	A002-C-205	Human	Colorectum	FAP	2.01e-17	-4.82e-01	-0.1236
23118	TAB2	A001-C-104	Human	Colorectum	FAP	1.25e-06	-3.19e-01	0.0184
23118	TAB2	A015-C-005	Human	Colorectum	FAP	1.50e-03	-3.23e-01	-0.0336
23118	TAB2	A015-C-006	Human	Colorectum	FAP	6.58e-14	-5.94e-01	-0.0994
23118	TAB2	A015-C-106	Human	Colorectum	FAP	4.43e-18	-4.47e-01	-0.0511
23118	TAB2	A002-C-114	Human	Colorectum	FAP	1.56e-16	-5.61e-01	-0.1561
23118	TAB2	A015-C-104	Human	Colorectum	FAP	1.57e-27	-5.48e-01	-0.1899
23118	TAB2	A001-C-014	Human	Colorectum	FAP	6.14e-18	-4.82e-01	0.0135
23118	TAB2	A002-C-016	Human	Colorectum	FAP	1.43e-20	-4.79e-01	0.0521
23118	TAB2	A015-C-002	Human	Colorectum	FAP	2.81e-11	-5.64e-01	-0.0763

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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
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

∗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:0009895	Colorectum	AD	negative regulation of catabolic process	124/3918	320/18723	1.66e-13	3.35e-11	124
GO:0031330	Colorectum	AD	negative regulation of cellular catabolic process	104/3918	262/18723	2.66e-12	3.96e-10	104
GO:0010506	Colorectum	AD	regulation of autophagy	111/3918	317/18723	3.57e-09	2.35e-07	111
GO:0033674	Colorectum	AD	positive regulation of kinase activity	131/3918	467/18723	1.28e-04	1.85e-03	131
GO:0043123	Colorectum	AD	positive regulation of I-kappaB kinase/NF-kappaB signaling	60/3918	186/18723	1.91e-04	2.56e-03	60
GO:0043122	Colorectum	AD	regulation of I-kappaB kinase/NF-kappaB signaling	76/3918	249/18723	2.17e-04	2.85e-03	76
GO:0007249	Colorectum	AD	I-kappaB kinase/NF-kappaB signaling	82/3918	281/18723	6.09e-04	6.40e-03	82
GO:0010507	Colorectum	AD	negative regulation of autophagy	31/3918	85/18723	6.91e-04	7.05e-03	31
GO:0045860	Colorectum	AD	positive regulation of protein kinase activity	107/3918	386/18723	8.01e-04	7.92e-03	107
GO:00098954	Colorectum	FAP	negative regulation of catabolic process	91/2622	320/18723	9.66e-12	4.96e-09	91
GO:00313304	Colorectum	FAP	negative regulation of cellular catabolic process	77/2622	262/18723	6.79e-11	2.31e-08	77
GO:00105063	Colorectum	FAP	regulation of autophagy	80/2622	317/18723	6.43e-08	4.54e-06	80
GO:00431222	Colorectum	FAP	regulation of I-kappaB kinase/NF-kappaB signaling	56/2622	249/18723	1.82e-04	2.69e-03	56
GO:00105072	Colorectum	FAP	negative regulation of autophagy	24/2622	85/18723	4.59e-04	5.39e-03	24
GO:00458604	Colorectum	FAP	positive regulation of protein kinase activity	77/2622	386/18723	7.31e-04	7.81e-03	77
GO:00431232	Colorectum	FAP	positive regulation of I-kappaB kinase/NF-kappaB signaling	42/2622	186/18723	1.01e-03	9.89e-03	42
GO:00336744	Colorectum	FAP	positive regulation of kinase activity	89/2622	467/18723	1.33e-03	1.22e-02	89
GO:00072492	Colorectum	FAP	I-kappaB kinase/NF-kappaB signaling	58/2622	281/18723	1.37e-03	1.24e-02	58
GO:00098955	Colorectum	CRC	negative regulation of catabolic process	75/2078	320/18723	2.02e-10	9.31e-08	75
GO:00313305	Colorectum	CRC	negative regulation of cellular catabolic process	61/2078	262/18723	1.27e-08	2.54e-06	61

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05171	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa05132	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa05135	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa05417	Colorectum	AD	Lipid and atherosclerosis	73/2092	215/8465	1.31e-03	8.27e-03	5.27e-03	73
hsa05170	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051711	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa051311	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa051321	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa051301	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa051351	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa054171	Colorectum	AD	Lipid and atherosclerosis	73/2092	215/8465	1.31e-03	8.27e-03	5.27e-03	73
hsa051701	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051718	Colorectum	FAP	Coronavirus disease - COVID-19	78/1404	232/8465	9.94e-11	1.11e-08	6.73e-09	78
hsa051318	Colorectum	FAP	Shigellosis	76/1404	247/8465	1.57e-08	5.84e-07	3.55e-07	76
hsa051308	Colorectum	FAP	Pathogenic Escherichia coli infection	62/1404	197/8465	1.37e-07	3.08e-06	1.87e-06	62
hsa051356	Colorectum	FAP	Yersinia infection	43/1404	137/8465	1.21e-05	1.62e-04	9.86e-05	43
hsa051328	Colorectum	FAP	Salmonella infection	67/1404	249/8465	2.04e-05	2.52e-04	1.53e-04	67
hsa054176	Colorectum	FAP	Lipid and atherosclerosis	54/1404	215/8465	8.04e-04	5.14e-03	3.13e-03	54

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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

TAB2

SNV

Missense_Mutation

novel

c.1276N>T

p.Val426Leu

p.V426L

Q9NYJ8

protein_coding

tolerated(0.42)

benign(0.003)

TCGA-A2-A25C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

TAB2

SNV

Missense_Mutation

c.928N>G

p.Ser310Gly

p.S310G

Q9NYJ8

protein_coding

tolerated(0.48)

benign(0)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TAB2

insertion

Frame_Shift_Ins

novel

c.1121dupC

p.Asn375LysfsTer4

p.N375Kfs*4

Q9NYJ8

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TAB2

insertion

Frame_Shift_Ins

novel

c.307_308insT

p.Thr104AsnfsTer5

p.T104Nfs*5

Q9NYJ8

protein_coding

TCGA-A8-A07G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

TAB2

insertion

Nonsense_Mutation

novel

c.461_462insAAGCGTGTGAAGGATTGAGATGACTGGTATGAAT

p.His154GlnfsTer4

p.H154Qfs*4

Q9NYJ8

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

TAB2

SNV

Missense_Mutation

rs775633022

c.1241N>C

p.Gly414Ala

p.G414A

Q9NYJ8

protein_coding

tolerated(0.51)

possibly_damaging(0.495)

TCGA-C5-A1MK-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

carboplatin

TAB2

SNV

Missense_Mutation

c.518N>C

p.Arg173Thr

p.R173T

Q9NYJ8

protein_coding

deleterious(0.03)

probably_damaging(0.966)

TCGA-EK-A3GJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TAB2

SNV

Missense_Mutation

c.1849C>G

p.Gln617Glu

p.Q617E

Q9NYJ8

protein_coding

deleterious(0.01)

possibly_damaging(0.608)

TCGA-LP-A4AX-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TAB2

SNV

Missense_Mutation

c.190N>C

p.Asp64His

p.D64H

Q9NYJ8

protein_coding

deleterious(0)

possibly_damaging(0.888)

TCGA-MY-A5BD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TAB2

insertion

Frame_Shift_Ins

novel

c.1687_1688insATTGTAAGTTTAGG

p.Ser563TyrfsTer15

p.S563Yfs*15

Q9NYJ8

protein_coding

TCGA-DS-A1OA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

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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
23118	TAB2	KINASE, DRUGGABLE GENOME		gefitinib	GEFITINIB	31664190

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