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: ATP6V0B

Gene summary for ATP6V0B

Gene summary.

Gene information	Species	Human
	Gene symbol	ATP6V0B
	Gene ID	533
	Gene name	ATPase H+ transporting V0 subunit b
	Gene Alias	ATP6F
	Cytomap	1p34.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q99437

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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
533	ATP6V0B	GSM4909282	Human	Breast	IDC	2.37e-05	3.57e-01	-0.0288
533	ATP6V0B	GSM4909285	Human	Breast	IDC	3.38e-02	1.77e-01	0.21
533	ATP6V0B	GSM4909286	Human	Breast	IDC	1.04e-05	-1.21e-01	0.1081
533	ATP6V0B	GSM4909293	Human	Breast	IDC	9.18e-04	2.48e-01	0.1581
533	ATP6V0B	GSM4909294	Human	Breast	IDC	3.37e-06	-1.91e-01	0.2022
533	ATP6V0B	GSM4909296	Human	Breast	IDC	4.02e-11	1.49e-01	0.1524
533	ATP6V0B	GSM4909297	Human	Breast	IDC	3.71e-15	-9.88e-02	0.1517
533	ATP6V0B	GSM4909298	Human	Breast	IDC	3.27e-09	-2.88e-01	0.1551
533	ATP6V0B	GSM4909301	Human	Breast	IDC	8.53e-03	1.82e-01	0.1577
533	ATP6V0B	GSM4909304	Human	Breast	IDC	3.85e-23	5.90e-01	0.1636
533	ATP6V0B	GSM4909311	Human	Breast	IDC	9.71e-40	-7.42e-02	0.1534
533	ATP6V0B	GSM4909312	Human	Breast	IDC	2.38e-23	4.14e-01	0.1552
533	ATP6V0B	GSM4909313	Human	Breast	IDC	3.70e-03	-1.95e-01	0.0391
533	ATP6V0B	GSM4909316	Human	Breast	IDC	3.09e-04	2.99e-02	0.21
533	ATP6V0B	GSM4909317	Human	Breast	IDC	7.33e-03	3.10e-01	0.1355
533	ATP6V0B	GSM4909319	Human	Breast	IDC	8.07e-53	-4.00e-02	0.1563
533	ATP6V0B	GSM4909320	Human	Breast	IDC	1.28e-06	-5.43e-03	0.1575
533	ATP6V0B	GSM4909321	Human	Breast	IDC	2.39e-14	-3.93e-02	0.1559
533	ATP6V0B	brca1	Human	Breast	Precancer	1.37e-24	6.35e-01	-0.0338
533	ATP6V0B	brca2	Human	Breast	Precancer	2.09e-10	3.59e-01	-0.024

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:19026008	Breast	Precancer	proton transmembrane transport	39/1080	157/18723	4.18e-15	1.18e-12	39
GO:190260012	Breast	IDC	proton transmembrane transport	40/1434	157/18723	7.34e-12	1.34e-09	40
GO:190260022	Breast	DCIS	proton transmembrane transport	40/1390	157/18723	2.77e-12	5.80e-10	40
GO:19026009	Cervix	CC	proton transmembrane transport	39/2311	157/18723	1.23e-05	2.57e-04	39
GO:00162367	Cervix	CC	macroautophagy	58/2311	291/18723	1.40e-04	1.70e-03	58
GO:00105067	Cervix	CC	regulation of autophagy	61/2311	317/18723	2.61e-04	2.87e-03	61
GO:1902600	Colorectum	AD	proton transmembrane transport	66/3918	157/18723	1.59e-09	1.17e-07	66
GO:0010506	Colorectum	AD	regulation of autophagy	111/3918	317/18723	3.57e-09	2.35e-07	111
GO:0016236	Colorectum	AD	macroautophagy	103/3918	291/18723	6.76e-09	4.15e-07	103
GO:0016241	Colorectum	AD	regulation of macroautophagy	50/3918	141/18723	4.55e-05	7.92e-04	50
GO:19026001	Colorectum	SER	proton transmembrane transport	60/2897	157/18723	3.12e-12	7.08e-10	60
GO:00162361	Colorectum	SER	macroautophagy	79/2897	291/18723	1.97e-07	1.10e-05	79
GO:00105061	Colorectum	SER	regulation of autophagy	74/2897	317/18723	1.39e-04	2.77e-03	74
GO:00162411	Colorectum	SER	regulation of macroautophagy	34/2897	141/18723	4.74e-03	3.72e-02	34
GO:00162362	Colorectum	MSS	macroautophagy	93/3467	291/18723	2.08e-08	1.17e-06	93
GO:19026002	Colorectum	MSS	proton transmembrane transport	57/3467	157/18723	1.00e-07	4.81e-06	57
GO:00105062	Colorectum	MSS	regulation of autophagy	95/3467	317/18723	4.36e-07	1.71e-05	95
GO:00162412	Colorectum	MSS	regulation of macroautophagy	44/3467	141/18723	1.88e-04	2.64e-03	44
GO:19026003	Colorectum	MSI-H	proton transmembrane transport	29/1319	157/18723	1.49e-06	9.75e-05	29
GO:190260010	Endometrium	AEH	proton transmembrane transport	43/2100	157/18723	1.70e-08	1.04e-06	43

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0019016	Breast	Precancer	Oxidative phosphorylation	59/684	134/8465	6.15e-30	3.24e-28	2.48e-28	59
hsa0511014	Breast	Precancer	Vibrio cholerae infection	14/684	50/8465	2.67e-05	2.64e-04	2.02e-04	14
hsa0414518	Breast	Precancer	Phagosome	27/684	152/8465	7.37e-05	6.85e-04	5.25e-04	27
hsa0532312	Breast	Precancer	Rheumatoid arthritis	19/684	93/8465	1.30e-04	1.14e-03	8.73e-04	19
hsa051206	Breast	Precancer	Epithelial cell signaling in Helicobacter pylori infection	14/684	70/8465	1.21e-03	7.99e-03	6.12e-03	14
hsa0019017	Breast	Precancer	Oxidative phosphorylation	59/684	134/8465	6.15e-30	3.24e-28	2.48e-28	59
hsa0511015	Breast	Precancer	Vibrio cholerae infection	14/684	50/8465	2.67e-05	2.64e-04	2.02e-04	14
hsa0414519	Breast	Precancer	Phagosome	27/684	152/8465	7.37e-05	6.85e-04	5.25e-04	27
hsa0532313	Breast	Precancer	Rheumatoid arthritis	19/684	93/8465	1.30e-04	1.14e-03	8.73e-04	19
hsa0512013	Breast	Precancer	Epithelial cell signaling in Helicobacter pylori infection	14/684	70/8465	1.21e-03	7.99e-03	6.12e-03	14
hsa0019023	Breast	IDC	Oxidative phosphorylation	62/867	134/8465	4.78e-27	2.59e-25	1.94e-25	62
hsa0511022	Breast	IDC	Vibrio cholerae infection	17/867	50/8465	4.82e-06	6.82e-05	5.10e-05	17
hsa0414522	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0532321	Breast	IDC	Rheumatoid arthritis	21/867	93/8465	3.69e-04	3.15e-03	2.36e-03	21
hsa0512022	Breast	IDC	Epithelial cell signaling in Helicobacter pylori infection	16/867	70/8465	1.56e-03	1.13e-02	8.42e-03	16
hsa0019033	Breast	IDC	Oxidative phosphorylation	62/867	134/8465	4.78e-27	2.59e-25	1.94e-25	62
hsa0511032	Breast	IDC	Vibrio cholerae infection	17/867	50/8465	4.82e-06	6.82e-05	5.10e-05	17
hsa0414532	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0532331	Breast	IDC	Rheumatoid arthritis	21/867	93/8465	3.69e-04	3.15e-03	2.36e-03	21
hsa0512032	Breast	IDC	Epithelial cell signaling in Helicobacter pylori infection	16/867	70/8465	1.56e-03	1.13e-02	8.42e-03	16

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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

ATP6V0B

SNV

Missense_Mutation

c.323N>A

p.Ala108Glu

p.A108E

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ATP6V0B

SNV

Missense_Mutation

novel

c.115T>C

p.Trp39Arg

p.W39R

protein_coding

tolerated(0.16)

benign(0.01)

TCGA-AC-A5EH-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATP6V0B

SNV

Missense_Mutation

novel

c.203G>T

p.Gly68Val

p.G68V

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AQ-A1H2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

herceptin

ATP6V0B

SNV

Missense_Mutation

novel

c.617N>A

p.Leu206Gln

p.L206Q

protein_coding

deleterious_low_confidence(0.04)

benign(0)

TCGA-D8-A13Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

ATP6V0B

SNV

Missense_Mutation

novel

c.127G>C

p.Glu43Gln

p.E43Q

protein_coding

tolerated(0.16)

benign(0.053)

TCGA-LL-A73Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

ATP6V0B

SNV

Missense_Mutation

novel

c.578T>C

p.Val193Ala

p.V193A

protein_coding

deleterious(0.02)

possibly_damaging(0.897)

TCGA-CM-5861-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

ATP6V0B

SNV

Missense_Mutation

c.586C>A

p.Leu196Ile

p.L196I

protein_coding

tolerated(0.41)

benign(0.23)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

ATP6V0B

SNV

Missense_Mutation

rs758360388

c.496N>A

p.Asp166Asn

p.D166N

protein_coding

deleterious(0.04)

probably_damaging(0.989)

TCGA-A5-A0VP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ATP6V0B

SNV

Missense_Mutation

novel

c.218G>A

p.Gly73Asp

p.G73D

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-AJ-A23O-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ATP6V0B

SNV

Missense_Mutation

rs775714078

c.553G>A

p.Ala185Thr

p.A185T

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

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

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