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: ATP5B

Gene summary for ATP5B

Gene summary.

Gene information	Species	Human
	Gene symbol	ATP5B
	Gene ID	506
	Gene name	ATP synthase F1 subunit beta
	Gene Alias	ATP5B
	Cytomap	12q13.3
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	P06576

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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
506	ATP5B	GSM4909281	Human	Breast	IDC	1.81e-17	-3.52e-01	0.21
506	ATP5B	GSM4909282	Human	Breast	IDC	9.36e-17	-3.52e-01	-0.0288
506	ATP5B	GSM4909285	Human	Breast	IDC	2.12e-16	-3.52e-01	0.21
506	ATP5B	GSM4909286	Human	Breast	IDC	9.36e-17	-3.52e-01	0.1081
506	ATP5B	GSM4909287	Human	Breast	IDC	1.12e-14	-3.52e-01	0.2057
506	ATP5B	GSM4909288	Human	Breast	IDC	1.24e-02	-3.52e-01	0.0988
506	ATP5B	GSM4909290	Human	Breast	IDC	3.25e-10	-3.52e-01	0.2096
506	ATP5B	GSM4909291	Human	Breast	IDC	4.44e-08	-3.52e-01	0.1753
506	ATP5B	GSM4909293	Human	Breast	IDC	9.36e-17	-3.52e-01	0.1581
506	ATP5B	GSM4909294	Human	Breast	IDC	1.81e-17	-3.52e-01	0.2022
506	ATP5B	GSM4909295	Human	Breast	IDC	4.00e-06	-3.52e-01	0.0898
506	ATP5B	GSM4909296	Human	Breast	IDC	4.80e-16	-3.52e-01	0.1524
506	ATP5B	GSM4909297	Human	Breast	IDC	2.86e-19	-3.52e-01	0.1517
506	ATP5B	GSM4909298	Human	Breast	IDC	7.93e-18	-3.52e-01	0.1551
506	ATP5B	GSM4909299	Human	Breast	IDC	4.12e-17	-3.52e-01	0.035
506	ATP5B	GSM4909300	Human	Breast	IDC	2.78e-05	-3.52e-01	0.0334
506	ATP5B	GSM4909301	Human	Breast	IDC	9.36e-17	-3.52e-01	0.1577
506	ATP5B	GSM4909302	Human	Breast	IDC	1.89e-14	-3.52e-01	0.1545
506	ATP5B	GSM4909303	Human	Breast	IDC	3.82e-03	-3.52e-01	0.0438
506	ATP5B	GSM4909304	Human	Breast	IDC	7.93e-18	-3.52e-01	0.1636

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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
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
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
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
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501420	Endometrium	AEH	Amyotrophic lateral sclerosis	123/1197	364/8465	2.17e-22	7.82e-21	5.72e-21	123
hsa0501020	Endometrium	AEH	Alzheimer disease	124/1197	384/8465	1.20e-20	3.91e-19	2.86e-19	124
hsa0471426	Endometrium	AEH	Thermogenesis	85/1197	232/8465	3.44e-18	9.33e-17	6.83e-17	85
hsa0502220	Endometrium	AEH	Pathways of neurodegeneration - multiple diseases	137/1197	476/8465	9.27e-18	2.32e-16	1.70e-16	137
hsa05012111	Endometrium	AEH	Parkinson disease	115/1197	266/8465	6.24e-32	1.01e-29	7.42e-30	115
hsa05020110	Endometrium	AEH	Prion disease	110/1197	273/8465	2.39e-27	2.44e-25	1.78e-25	110
hsa05016110	Endometrium	AEH	Huntington disease	118/1197	306/8465	3.00e-27	2.44e-25	1.78e-25	118
hsa00190110	Endometrium	AEH	Oxidative phosphorylation	69/1197	134/8465	5.80e-25	3.14e-23	2.30e-23	69
hsa05415111	Endometrium	AEH	Diabetic cardiomyopathy	86/1197	203/8465	2.62e-23	1.22e-21	8.90e-22	86
hsa05208112	Endometrium	AEH	Chemical carcinogenesis - reactive oxygen species	91/1197	223/8465	3.28e-23	1.33e-21	9.76e-22	91
hsa05014110	Endometrium	AEH	Amyotrophic lateral sclerosis	123/1197	364/8465	2.17e-22	7.82e-21	5.72e-21	123
hsa05010110	Endometrium	AEH	Alzheimer disease	124/1197	384/8465	1.20e-20	3.91e-19	2.86e-19	124
hsa04714111	Endometrium	AEH	Thermogenesis	85/1197	232/8465	3.44e-18	9.33e-17	6.83e-17	85
hsa05022110	Endometrium	AEH	Pathways of neurodegeneration - multiple diseases	137/1197	476/8465	9.27e-18	2.32e-16	1.70e-16	137
hsa0501227	Endometrium	EEC	Parkinson disease	117/1237	266/8465	5.97e-32	9.82e-30	7.32e-30	117
hsa0501625	Endometrium	EEC	Huntington disease	120/1237	306/8465	3.86e-27	4.23e-25	3.15e-25	120
hsa0502025	Endometrium	EEC	Prion disease	111/1237	273/8465	1.01e-26	8.27e-25	6.16e-25	111
hsa0019025	Endometrium	EEC	Oxidative phosphorylation	70/1237	134/8465	6.33e-25	3.47e-23	2.59e-23	70
hsa0520827	Endometrium	EEC	Chemical carcinogenesis - reactive oxygen species	94/1237	223/8465	4.11e-24	1.93e-22	1.44e-22	94
hsa0501425	Endometrium	EEC	Amyotrophic lateral sclerosis	128/1237	364/8465	9.83e-24	4.04e-22	3.01e-22	128

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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

ATP5B

SNV

Missense_Mutation

c.460N>A

p.Glu154Lys

p.E154K

P06576

protein_coding

deleterious_low_confidence(0)

benign(0.323)

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

ATP5B

SNV

Missense_Mutation

c.1030G>C

p.Glu344Gln

p.E344Q

P06576

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.977)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

ATP5B

deletion

Frame_Shift_Del

novel

c.1088delN

p.Pro363LeufsTer5

p.P363Lfs*5

P06576

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ATP5B

SNV

Missense_Mutation

rs2293450

c.74N>T

p.Ser25Leu

p.S25L

P06576

protein_coding

tolerated_low_confidence(0.78)

benign(0.005)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

ATP5B

SNV

Missense_Mutation

novel

c.1360N>A

p.Val454Met

p.V454M

P06576

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.927)

TCGA-AA-3950-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

ATP5B

SNV

Missense_Mutation

rs777770019

c.1255N>A

p.Asp419Asn

p.D419N

P06576

protein_coding

tolerated_low_confidence(0.5)

benign(0.001)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

ATP5B

SNV

Missense_Mutation

c.298G>A

p.Ala100Thr

p.A100T

P06576

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.75)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

ATP5B

SNV

Missense_Mutation

c.968N>A

p.Gly323Asp

p.G323D

P06576

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.957)

TCGA-D5-6927-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

ATP5B

SNV

Missense_Mutation

c.992A>G

p.Tyr331Cys

p.Y331C

P06576

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-DM-A28E-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

ATP5B

SNV

Missense_Mutation

c.1124N>T

p.Thr375Met

p.T375M

P06576

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-DM-A28G-01

Colorectum

colon adenocarcinoma

Male

>=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

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