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:0046034	Colorectum	AD	ATP metabolic process	142/3918	277/18723	2.64e-29	8.26e-26	142
GO:0006091	Colorectum	AD	generation of precursor metabolites and energy	209/3918	490/18723	3.17e-28	6.61e-25	209
GO:0009060	Colorectum	AD	aerobic respiration	108/3918	189/18723	9.14e-28	1.43e-24	108
GO:0045333	Colorectum	AD	cellular respiration	119/3918	230/18723	3.21e-25	4.02e-22	119
GO:0006119	Colorectum	AD	oxidative phosphorylation	83/3918	141/18723	7.95e-23	8.30e-20	83
GO:0015980	Colorectum	AD	energy derivation by oxidation of organic compounds	143/3918	318/18723	2.78e-22	2.49e-19	143
GO:0009150	Colorectum	AD	purine ribonucleotide metabolic process	142/3918	368/18723	4.29e-15	1.17e-12	142
GO:0006163	Colorectum	AD	purine nucleotide metabolic process	149/3918	396/18723	1.08e-14	2.80e-12	149
GO:0072521	Colorectum	AD	purine-containing compound metabolic process	153/3918	416/18723	4.34e-14	1.01e-11	153
GO:0009259	Colorectum	AD	ribonucleotide metabolic process	144/3918	385/18723	5.25e-14	1.13e-11	144
GO:0019693	Colorectum	AD	ribose phosphate metabolic process	145/3918	396/18723	3.01e-13	5.71e-11	145
GO:0006839	Colorectum	AD	mitochondrial transport	102/3918	254/18723	1.87e-12	3.08e-10	102
GO:0009117	Colorectum	AD	nucleotide metabolic process	168/3918	489/18723	2.20e-12	3.36e-10	168
GO:0006753	Colorectum	AD	nucleoside phosphate metabolic process	169/3918	497/18723	4.99e-12	6.98e-10	169
GO:1902600	Colorectum	AD	proton transmembrane transport	66/3918	157/18723	1.59e-09	1.17e-07	66
GO:0009144	Colorectum	AD	purine nucleoside triphosphate metabolic process	43/3918	88/18723	5.05e-09	3.19e-07	43
GO:1990542	Colorectum	AD	mitochondrial transmembrane transport	47/3918	102/18723	1.09e-08	6.52e-07	47
GO:0009205	Colorectum	AD	purine ribonucleoside triphosphate metabolic process	39/3918	82/18723	6.58e-08	3.40e-06	39
GO:0009141	Colorectum	AD	nucleoside triphosphate metabolic process	48/3918	112/18723	1.27e-07	6.02e-06	48
GO:0006754	Colorectum	AD	ATP biosynthetic process	30/3918	57/18723	1.27e-07	6.02e-06	30

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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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