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: ATP5F1EP2

Gene summary for ATP5F1EP2

Gene summary.

Gene information	Species	Human
	Gene symbol	ATP5F1EP2
	Gene ID	432369
	Gene name	ATP synthase F1 subunit epsilon pseudogene 2
	Gene Alias	ATP5EP2
	Cytomap	13q12.2
	Gene Type	pseudo
	GO ID	GO:0006091
	UniProtAcc	NA

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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
432369	ATP5F1EP2	HTA11_3410_2000001011	Human	Colorectum	AD	8.85e-17	3.29e-01	0.0155
432369	ATP5F1EP2	HTA11_2487_2000001011	Human	Colorectum	SER	6.14e-31	6.92e-01	-0.1808
432369	ATP5F1EP2	HTA11_2951_2000001011	Human	Colorectum	AD	6.82e-15	6.95e-01	0.0216
432369	ATP5F1EP2	HTA11_1938_2000001011	Human	Colorectum	AD	7.67e-28	8.24e-01	-0.0811
432369	ATP5F1EP2	HTA11_78_2000001011	Human	Colorectum	AD	8.35e-11	2.63e-01	-0.1088
432369	ATP5F1EP2	HTA11_347_2000001011	Human	Colorectum	AD	1.56e-54	9.16e-01	-0.1954
432369	ATP5F1EP2	HTA11_411_2000001011	Human	Colorectum	SER	3.12e-22	1.07e+00	-0.2602
432369	ATP5F1EP2	HTA11_2112_2000001011	Human	Colorectum	SER	2.67e-18	9.22e-01	-0.2196
432369	ATP5F1EP2	HTA11_3361_2000001011	Human	Colorectum	AD	1.63e-41	9.15e-01	-0.1207
432369	ATP5F1EP2	HTA11_83_2000001011	Human	Colorectum	SER	1.34e-31	1.01e+00	-0.1526
432369	ATP5F1EP2	HTA11_696_2000001011	Human	Colorectum	AD	9.08e-52	8.73e-01	-0.1464
432369	ATP5F1EP2	HTA11_866_2000001011	Human	Colorectum	AD	1.28e-34	6.29e-01	-0.1001
432369	ATP5F1EP2	HTA11_1391_2000001011	Human	Colorectum	AD	2.14e-46	1.04e+00	-0.059
432369	ATP5F1EP2	HTA11_2992_2000001011	Human	Colorectum	SER	4.22e-23	9.71e-01	-0.1706
432369	ATP5F1EP2	HTA11_5212_2000001011	Human	Colorectum	AD	2.59e-17	6.19e-01	-0.2061
432369	ATP5F1EP2	HTA11_5216_2000001011	Human	Colorectum	SER	1.51e-11	6.52e-01	-0.1462
432369	ATP5F1EP2	HTA11_546_2000001011	Human	Colorectum	AD	1.19e-22	7.26e-01	-0.0842
432369	ATP5F1EP2	HTA11_9341_2000001011	Human	Colorectum	SER	1.35e-12	6.31e-01	-0.00410000000000005
432369	ATP5F1EP2	HTA11_7862_2000001011	Human	Colorectum	AD	3.18e-15	5.71e-01	-0.0179
432369	ATP5F1EP2	HTA11_866_3004761011	Human	Colorectum	AD	1.32e-44	8.09e-01	0.096

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

∗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:00159801	Colorectum	SER	energy derivation by oxidation of organic compounds	119/2897	318/18723	5.28e-22	4.62e-19	119
GO:00068391	Colorectum	SER	mitochondrial transport	87/2897	254/18723	7.91e-14	3.03e-11	87
GO:19026001	Colorectum	SER	proton transmembrane transport	60/2897	157/18723	3.12e-12	7.08e-10	60
GO:19905421	Colorectum	SER	mitochondrial transmembrane transport	42/2897	102/18723	3.65e-10	4.77e-08	42
GO:00061631	Colorectum	SER	purine nucleotide metabolic process	109/2897	396/18723	4.26e-10	5.44e-08	109
GO:00091501	Colorectum	SER	purine ribonucleotide metabolic process	103/2897	368/18723	4.69e-10	5.68e-08	103
GO:00725211	Colorectum	SER	purine-containing compound metabolic process	113/2897	416/18723	4.80e-10	5.68e-08	113
GO:00091441	Colorectum	SER	purine nucleoside triphosphate metabolic process	38/2897	88/18723	4.82e-10	5.68e-08	38
GO:00092591	Colorectum	SER	ribonucleotide metabolic process	104/2897	385/18723	3.27e-09	3.04e-07	104
GO:00091451	Colorectum	SER	purine nucleoside triphosphate biosynthetic process	31/2897	69/18723	5.91e-09	5.25e-07	31
GO:00196931	Colorectum	SER	ribose phosphate metabolic process	105/2897	396/18723	8.15e-09	7.14e-07	105
GO:00159851	Colorectum	SER	energy coupled proton transport, down electrochemical gradient	17/2897	26/18723	1.22e-08	9.74e-07	17
GO:00159861	Colorectum	SER	ATP synthesis coupled proton transport	17/2897	26/18723	1.22e-08	9.74e-07	17
GO:00092051	Colorectum	SER	purine ribonucleoside triphosphate metabolic process	34/2897	82/18723	1.37e-08	1.05e-06	34
GO:00067541	Colorectum	SER	ATP biosynthetic process	27/2897	57/18723	1.38e-08	1.05e-06	27
GO:00092061	Colorectum	SER	purine ribonucleoside triphosphate biosynthetic process	30/2897	68/18723	1.74e-08	1.28e-06	30
GO:00427761	Colorectum	SER	mitochondrial ATP synthesis coupled proton transport	14/2897	19/18723	2.35e-08	1.68e-06	14
GO:00091171	Colorectum	SER	nucleotide metabolic process	122/2897	489/18723	2.50e-08	1.76e-06	122
GO:00091411	Colorectum	SER	nucleoside triphosphate metabolic process	41/2897	112/18723	3.46e-08	2.31e-06	41
GO:00067531	Colorectum	SER	nucleoside phosphate metabolic process	122/2897	497/18723	6.64e-08	4.33e-06	122

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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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