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: ATP5MF

Gene summary for ATP5MF

Gene summary.

Gene information	Species	Human
	Gene symbol	ATP5MF
	Gene ID	9551
	Gene name	ATP synthase membrane subunit f
	Gene Alias	ATP5J2
	Cytomap	7q22.1
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	P56134

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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
9551	ATP5MF	NCCBC5	Human	Breast	DCIS	4.87e-19	4.93e-01	0.2046
9551	ATP5MF	P1	Human	Breast	IDC	2.92e-12	-1.69e-01	0.1527
9551	ATP5MF	P2	Human	Breast	IDC	4.32e-07	4.71e-01	0.21
9551	ATP5MF	DCIS2	Human	Breast	DCIS	4.24e-70	2.37e-01	0.0085
9551	ATP5MF	CA_HPV_1	Human	Cervix	CC	4.03e-11	-8.87e-02	0.0264
9551	ATP5MF	CA_HPV_3	Human	Cervix	CC	4.25e-03	-1.36e-01	0.0414
9551	ATP5MF	CCI_1	Human	Cervix	CC	5.96e-22	-9.89e-01	0.528
9551	ATP5MF	CCI_2	Human	Cervix	CC	2.13e-20	-9.89e-01	0.5249
9551	ATP5MF	CCI_3	Human	Cervix	CC	3.74e-28	-9.89e-01	0.516
9551	ATP5MF	CCII_1	Human	Cervix	CC	1.66e-37	-9.89e-01	0.3249
9551	ATP5MF	Tumor	Human	Cervix	CC	4.23e-74	-9.89e-01	0.1241
9551	ATP5MF	L1	Human	Cervix	CC	2.28e-08	-1.85e-01	0.0802
9551	ATP5MF	T1	Human	Cervix	CC	2.12e-02	-3.06e-01	0.0918
9551	ATP5MF	T3	Human	Cervix	CC	9.44e-03	2.02e-01	0.1389
9551	ATP5MF	HTA11_3410_2000001011	Human	Colorectum	AD	7.05e-23	3.90e-01	0.0155
9551	ATP5MF	HTA11_2487_2000001011	Human	Colorectum	SER	1.16e-43	1.06e+00	-0.1808
9551	ATP5MF	HTA11_2951_2000001011	Human	Colorectum	AD	3.34e-04	3.08e-01	0.0216
9551	ATP5MF	HTA11_1938_2000001011	Human	Colorectum	AD	5.76e-31	9.32e-01	-0.0811
9551	ATP5MF	HTA11_78_2000001011	Human	Colorectum	AD	4.79e-18	4.61e-01	-0.1088
9551	ATP5MF	HTA11_347_2000001011	Human	Colorectum	AD	1.60e-52	8.91e-01	-0.1954

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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
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
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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:00061199	Breast	Precancer	oxidative phosphorylation	53/1080	141/18723	1.15e-29	2.04e-26	53
GO:00090608	Breast	Precancer	aerobic respiration	58/1080	189/18723	5.69e-27	7.62e-24	58
GO:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00453338	Breast	Precancer	cellular respiration	59/1080	230/18723	5.97e-23	5.32e-20	59
GO:00159808	Breast	Precancer	energy derivation by oxidation of organic compounds	70/1080	318/18723	8.33e-23	6.37e-20	70
GO:19026008	Breast	Precancer	proton transmembrane transport	39/1080	157/18723	4.18e-15	1.18e-12	39
GO:00159857	Breast	Precancer	energy coupled proton transport, down electrochemical gradient	16/1080	26/18723	4.15e-14	9.65e-12	16
GO:00159867	Breast	Precancer	ATP synthesis coupled proton transport	16/1080	26/18723	4.15e-14	9.65e-12	16
GO:00427766	Breast	Precancer	mitochondrial ATP synthesis coupled proton transport	13/1080	19/18723	1.43e-12	2.74e-10	13
GO:00067547	Breast	Precancer	ATP biosynthetic process	21/1080	57/18723	2.31e-12	4.26e-10	21
GO:00068398	Breast	Precancer	mitochondrial transport	45/1080	254/18723	1.37e-11	1.88e-09	45
GO:00092067	Breast	Precancer	purine ribonucleoside triphosphate biosynthetic process	22/1080	68/18723	1.41e-11	1.88e-09	22
GO:00091457	Breast	Precancer	purine nucleoside triphosphate biosynthetic process	22/1080	69/18723	1.95e-11	2.43e-09	22
GO:00092017	Breast	Precancer	ribonucleoside triphosphate biosynthetic process	22/1080	74/18723	9.18e-11	1.00e-08	22
GO:00091448	Breast	Precancer	purine nucleoside triphosphate metabolic process	24/1080	88/18723	9.66e-11	1.03e-08	24
GO:00092057	Breast	Precancer	purine ribonucleoside triphosphate metabolic process	23/1080	82/18723	1.27e-10	1.34e-08	23
GO:00091427	Breast	Precancer	nucleoside triphosphate biosynthetic process	23/1080	85/18723	2.82e-10	2.69e-08	23
GO:00091997	Breast	Precancer	ribonucleoside triphosphate metabolic process	23/1080	89/18723	7.65e-10	6.66e-08	23
GO:00091418	Breast	Precancer	nucleoside triphosphate metabolic process	26/1080	112/18723	7.72e-10	6.66e-08	26

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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
hsa0471418	Breast	Precancer	Thermogenesis	68/684	232/8465	4.40e-22	1.26e-20	9.69e-21	68
hsa0019017	Breast	Precancer	Oxidative phosphorylation	59/684	134/8465	6.15e-30	3.24e-28	2.48e-28	59
hsa0471419	Breast	Precancer	Thermogenesis	68/684	232/8465	4.40e-22	1.26e-20	9.69e-21	68
hsa0019023	Breast	IDC	Oxidative phosphorylation	62/867	134/8465	4.78e-27	2.59e-25	1.94e-25	62
hsa0471424	Breast	IDC	Thermogenesis	75/867	232/8465	8.41e-21	3.04e-19	2.27e-19	75
hsa0019033	Breast	IDC	Oxidative phosphorylation	62/867	134/8465	4.78e-27	2.59e-25	1.94e-25	62
hsa0471434	Breast	IDC	Thermogenesis	75/867	232/8465	8.41e-21	3.04e-19	2.27e-19	75
hsa0019043	Breast	DCIS	Oxidative phosphorylation	61/846	134/8465	9.84e-27	5.30e-25	3.90e-25	61
hsa0471443	Breast	DCIS	Thermogenesis	74/846	232/8465	8.72e-21	3.13e-19	2.30e-19	74
hsa0019053	Breast	DCIS	Oxidative phosphorylation	61/846	134/8465	9.84e-27	5.30e-25	3.90e-25	61
hsa0471453	Breast	DCIS	Thermogenesis	74/846	232/8465	8.72e-21	3.13e-19	2.30e-19	74
hsa0019018	Cervix	CC	Oxidative phosphorylation	64/1267	134/8465	1.25e-19	8.07e-18	4.77e-18	64
hsa0471420	Cervix	CC	Thermogenesis	76/1267	232/8465	4.29e-12	1.16e-10	6.85e-11	76
hsa0019019	Cervix	CC	Oxidative phosphorylation	64/1267	134/8465	1.25e-19	8.07e-18	4.77e-18	64
hsa04714110	Cervix	CC	Thermogenesis	76/1267	232/8465	4.29e-12	1.16e-10	6.85e-11	76
hsa00190	Colorectum	AD	Oxidative phosphorylation	86/2092	134/8465	2.47e-22	2.76e-20	1.76e-20	86
hsa04714	Colorectum	AD	Thermogenesis	120/2092	232/8465	2.76e-19	1.16e-17	7.37e-18	120
hsa001901	Colorectum	AD	Oxidative phosphorylation	86/2092	134/8465	2.47e-22	2.76e-20	1.76e-20	86
hsa047141	Colorectum	AD	Thermogenesis	120/2092	232/8465	2.76e-19	1.16e-17	7.37e-18	120

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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

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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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