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: ATP5IF1

Gene summary for ATP5IF1

Gene summary.

Gene information	Species	Human
	Gene symbol	ATP5IF1
	Gene ID	93974
	Gene name	ATP synthase inhibitory factor subunit 1
	Gene Alias	ATPI
	Cytomap	1p35.3
	Gene Type	protein-coding
	GO ID	GO:0000422
	UniProtAcc	Q9UII2

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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
93974	ATP5IF1	Dong_P3	Human	Prostate	Tumor	2.34e-16	-5.82e-01	0.0278
93974	ATP5IF1	Dong_P4	Human	Prostate	Tumor	1.26e-04	-5.82e-01	0.0292
93974	ATP5IF1	Dong_P5	Human	Prostate	Tumor	3.21e-26	5.57e-01	0.053
93974	ATP5IF1	Dong_P6	Human	Prostate	Tumor	6.90e-09	5.40e-01	0.0371
93974	ATP5IF1	P7	Human	Prostate	Tumor	3.06e-05	-5.82e-01	-0.1025
93974	ATP5IF1	P9	Human	Prostate	Tumor	2.35e-11	-5.82e-01	-0.0285
93974	ATP5IF1	P10	Human	Prostate	Tumor	1.16e-12	-5.82e-01	-0.0902
93974	ATP5IF1	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	2.55e-09	-5.82e-01	0.1633
93974	ATP5IF1	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	8.39e-14	-5.82e-01	0.1608
93974	ATP5IF1	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	1.28e-07	-5.82e-01	0.1604
93974	ATP5IF1	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	2.46e-08	-5.82e-01	0.1621
93974	ATP5IF1	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	1.60e-03	-5.82e-01	0.1619
93974	ATP5IF1	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	7.15e-10	-5.82e-01	0.1602
93974	ATP5IF1	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	5.34e-04	-5.82e-01	0.1608
93974	ATP5IF1	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	4.03e-16	-5.82e-01	0.1575
93974	ATP5IF1	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	7.22e-18	-5.82e-01	0.1545
93974	ATP5IF1	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	2.00e-13	-5.82e-01	0.1569
93974	ATP5IF1	P1_S1_AK	Human	Skin	AK	1.88e-11	3.44e-01	-0.3399
93974	ATP5IF1	P2_S3_AK	Human	Skin	AK	3.08e-18	4.23e-01	-0.3287
93974	ATP5IF1	P2_S4_SCCIS	Human	Skin	SCCIS	1.86e-05	3.63e-01	-0.3043

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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:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00068398	Breast	Precancer	mitochondrial transport	45/1080	254/18723	1.37e-11	1.88e-09	45
GO:00458629	Breast	Precancer	positive regulation of proteolysis	51/1080	372/18723	7.77e-09	5.70e-07	51
GO:00086378	Breast	Precancer	apoptotic mitochondrial changes	23/1080	107/18723	3.44e-08	2.12e-06	23
GO:00513468	Breast	Precancer	negative regulation of hydrolase activity	50/1080	379/18723	3.85e-08	2.34e-06	50
GO:00518816	Breast	Precancer	regulation of mitochondrial membrane potential	18/1080	74/18723	1.45e-07	7.82e-06	18
GO:00022629	Breast	Precancer	myeloid cell homeostasis	27/1080	157/18723	3.10e-07	1.49e-05	27
GO:19033629	Breast	Precancer	regulation of cellular protein catabolic process	36/1080	255/18723	6.03e-07	2.55e-05	36
GO:00341019	Breast	Precancer	erythrocyte homeostasis	23/1080	129/18723	1.20e-06	4.60e-05	23
GO:00421769	Breast	Precancer	regulation of protein catabolic process	47/1080	391/18723	1.50e-06	5.58e-05	47
GO:00300999	Breast	Precancer	myeloid cell differentiation	45/1080	381/18723	4.00e-06	1.25e-04	45
GO:19030509	Breast	Precancer	regulation of proteolysis involved in cellular protein catabolic process	31/1080	221/18723	4.10e-06	1.27e-04	31
GO:00705858	Breast	Precancer	protein localization to mitochondrion	21/1080	125/18723	9.07e-06	2.42e-04	21
GO:00070066	Breast	Precancer	mitochondrial membrane organization	20/1080	116/18723	9.88e-06	2.61e-04	20
GO:00726558	Breast	Precancer	establishment of protein localization to mitochondrion	20/1080	120/18723	1.66e-05	4.03e-04	20
GO:00905595	Breast	Precancer	regulation of membrane permeability	15/1080	78/18723	3.35e-05	7.29e-04	15
GO:00725938	Breast	Precancer	reactive oxygen species metabolic process	30/1080	239/18723	5.13e-05	1.07e-03	30
GO:00469025	Breast	Precancer	regulation of mitochondrial membrane permeability	13/1080	63/18723	5.13e-05	1.07e-03	13
GO:00506736	Breast	Precancer	epithelial cell proliferation	46/1080	437/18723	6.02e-05	1.23e-03	46

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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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