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: ATP5ME

Gene summary for ATP5ME

Gene summary.

Gene information	Species	Human
	Gene symbol	ATP5ME
	Gene ID	521
	Gene name	ATP synthase membrane subunit e
	Gene Alias	ATP5I
	Cytomap	4p16.3
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	P56385

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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
521	ATP5ME	GSM4909281	Human	Breast	IDC	2.48e-11	3.75e-01	0.21
521	ATP5ME	GSM4909282	Human	Breast	IDC	1.13e-12	4.36e-01	-0.0288
521	ATP5ME	GSM4909285	Human	Breast	IDC	1.16e-15	-1.17e-01	0.21
521	ATP5ME	GSM4909286	Human	Breast	IDC	2.99e-16	-1.17e-01	0.1081
521	ATP5ME	GSM4909287	Human	Breast	IDC	1.75e-05	4.12e-01	0.2057
521	ATP5ME	GSM4909290	Human	Breast	IDC	3.41e-03	2.22e-01	0.2096
521	ATP5ME	GSM4909291	Human	Breast	IDC	1.34e-08	5.15e-01	0.1753
521	ATP5ME	GSM4909293	Human	Breast	IDC	1.15e-44	7.80e-01	0.1581
521	ATP5ME	GSM4909294	Human	Breast	IDC	7.16e-24	7.00e-01	0.2022
521	ATP5ME	GSM4909295	Human	Breast	IDC	3.81e-03	3.88e-01	0.0898
521	ATP5ME	GSM4909297	Human	Breast	IDC	2.07e-04	2.47e-01	0.1517
521	ATP5ME	GSM4909298	Human	Breast	IDC	1.14e-24	4.58e-01	0.1551
521	ATP5ME	GSM4909299	Human	Breast	IDC	4.58e-13	3.94e-01	0.035
521	ATP5ME	GSM4909300	Human	Breast	IDC	9.60e-03	3.74e-01	0.0334
521	ATP5ME	GSM4909301	Human	Breast	IDC	4.59e-49	8.65e-01	0.1577
521	ATP5ME	GSM4909303	Human	Breast	IDC	5.81e-08	6.37e-01	0.0438
521	ATP5ME	GSM4909304	Human	Breast	IDC	2.38e-55	8.84e-01	0.1636
521	ATP5ME	GSM4909305	Human	Breast	IDC	1.18e-05	1.65e-01	0.0436
521	ATP5ME	GSM4909306	Human	Breast	IDC	1.18e-23	6.37e-01	0.1564
521	ATP5ME	GSM4909308	Human	Breast	IDC	1.34e-11	-6.80e-02	0.158

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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
hsa0019024	Cervix	HSIL_HPV	Oxidative phosphorylation	25/459	134/8465	4.23e-08	1.55e-06	1.25e-06	25
hsa0471425	Cervix	HSIL_HPV	Thermogenesis	25/459	232/8465	7.63e-04	5.88e-03	4.76e-03	25
hsa0019034	Cervix	HSIL_HPV	Oxidative phosphorylation	25/459	134/8465	4.23e-08	1.55e-06	1.25e-06	25
hsa0471435	Cervix	HSIL_HPV	Thermogenesis	25/459	232/8465	7.63e-04	5.88e-03	4.76e-03	25

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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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