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: EVI5

Gene summary for EVI5

Gene summary.

Gene information	Species	Human
	Gene symbol	EVI5
	Gene ID	7813
	Gene name	ecotropic viral integration site 5
	Gene Alias	EVI-5
	Cytomap	1p22.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	O60447

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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
7813	EVI5	CCI_1	Human	Cervix	CC	6.51e-04	8.29e-01	0.528
7813	EVI5	CCI_2	Human	Cervix	CC	4.60e-02	5.70e-01	0.5249
7813	EVI5	HTA11_3410_2000001011	Human	Colorectum	AD	9.98e-22	-6.49e-01	0.0155
7813	EVI5	HTA11_3361_2000001011	Human	Colorectum	AD	1.97e-02	-5.03e-01	-0.1207
7813	EVI5	HTA11_83_2000001011	Human	Colorectum	SER	4.64e-07	-2.41e-01	-0.1526
7813	EVI5	HTA11_696_2000001011	Human	Colorectum	AD	2.18e-02	-2.54e-01	-0.1464
7813	EVI5	HTA11_5212_2000001011	Human	Colorectum	AD	2.40e-04	-4.57e-01	-0.2061
7813	EVI5	HTA11_5216_2000001011	Human	Colorectum	SER	1.45e-02	-6.02e-01	-0.1462
7813	EVI5	HTA11_9341_2000001011	Human	Colorectum	SER	9.63e-04	-6.55e-01	-0.00410000000000005
7813	EVI5	HTA11_866_3004761011	Human	Colorectum	AD	6.27e-10	-6.16e-01	0.096
7813	EVI5	HTA11_8622_2000001021	Human	Colorectum	SER	1.02e-07	-7.47e-01	0.0528
7813	EVI5	HTA11_10711_2000001011	Human	Colorectum	AD	2.52e-05	-4.90e-01	0.0338
7813	EVI5	HTA11_7696_3000711011	Human	Colorectum	AD	4.84e-08	-4.78e-01	0.0674
7813	EVI5	HTA11_6818_2000001021	Human	Colorectum	AD	3.17e-04	-4.44e-01	0.0588
7813	EVI5	HTA11_99999970781_79442	Human	Colorectum	MSS	4.97e-27	-5.72e-01	0.294
7813	EVI5	HTA11_99999971662_82457	Human	Colorectum	MSS	8.37e-03	-3.32e-01	0.3859
7813	EVI5	HTA11_99999973899_84307	Human	Colorectum	MSS	9.37e-10	-6.94e-01	0.2585
7813	EVI5	HTA11_99999974143_84620	Human	Colorectum	MSS	3.72e-26	-6.80e-01	0.3005
7813	EVI5	A001-C-207	Human	Colorectum	FAP	2.56e-05	-3.73e-01	0.1278
7813	EVI5	A015-C-203	Human	Colorectum	FAP	4.82e-33	-5.30e-01	-0.1294

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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
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:00161973	Colorectum	FAP	endosomal transport	56/2622	230/18723	1.79e-05	4.53e-04	56
GO:00421472	Colorectum	FAP	retrograde transport, endosome to Golgi	26/2622	91/18723	2.21e-04	3.14e-03	26
GO:0090630	Colorectum	FAP	activation of GTPase activity	27/2622	115/18723	4.23e-03	2.90e-02	27
GO:00164824	Colorectum	CRC	cytosolic transport	45/2078	168/18723	1.22e-08	2.52e-06	45
GO:00430874	Colorectum	CRC	regulation of GTPase activity	69/2078	348/18723	1.11e-06	6.69e-05	69
GO:00161974	Colorectum	CRC	endosomal transport	49/2078	230/18723	5.07e-06	2.05e-04	49
GO:00421473	Colorectum	CRC	retrograde transport, endosome to Golgi	24/2078	91/18723	3.88e-05	9.49e-04	24
GO:00435473	Colorectum	CRC	positive regulation of GTPase activity	49/2078	255/18723	8.67e-05	1.77e-03	49
GO:00430878	Endometrium	AEH	regulation of GTPase activity	66/2100	348/18723	1.26e-05	2.77e-04	66
GO:00435477	Endometrium	AEH	positive regulation of GTPase activity	48/2100	255/18723	2.18e-04	2.67e-03	48
GO:00906304	Endometrium	AEH	activation of GTPase activity	22/2100	115/18723	8.42e-03	4.60e-02	22
GO:004308712	Endometrium	EEC	regulation of GTPase activity	67/2168	348/18723	1.84e-05	3.43e-04	67
GO:004354712	Endometrium	EEC	positive regulation of GTPase activity	50/2168	255/18723	1.26e-04	1.66e-03	50
GO:009063012	Endometrium	EEC	activation of GTPase activity	23/2168	115/18723	6.04e-03	3.57e-02	23
GO:001619715	Esophagus	ESCC	endosomal transport	168/8552	230/18723	2.28e-17	1.93e-15	168
GO:001648210	Esophagus	ESCC	cytosolic transport	124/8552	168/18723	9.69e-14	4.69e-12	124
GO:00421477	Esophagus	ESCC	retrograde transport, endosome to Golgi	63/8552	91/18723	4.58e-06	4.87e-05	63
GO:004308715	Esophagus	ESCC	regulation of GTPase activity	183/8552	348/18723	5.34e-03	2.00e-02	183
GO:00430875	Liver	NAFLD	regulation of GTPase activity	62/1882	348/18723	5.65e-06	2.03e-04	62
GO:00164825	Liver	NAFLD	cytosolic transport	34/1882	168/18723	5.52e-05	1.25e-03	34

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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

EVI5

SNV

Missense_Mutation

c.663N>G

p.Ser221Arg

p.S221R

O60447

protein_coding

tolerated(0.06)

probably_damaging(0.962)

TCGA-A8-A092-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

EVI5

SNV

Missense_Mutation

novel

c.1155N>A

p.His385Gln

p.H385Q

O60447

protein_coding

tolerated(0.2)

probably_damaging(0.948)

TCGA-AC-A2BK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

EVI5

SNV

Missense_Mutation

c.365C>T

p.Ser122Leu

p.S122L

O60447

protein_coding

deleterious(0.02)

probably_damaging(0.945)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

EVI5

insertion

Frame_Shift_Ins

novel

c.2416_2417insTGCGTGTCACAGCAACACTCTGTCTCAA

p.Gln806LeufsTer32

p.Q806Lfs*32

O60447

protein_coding

TCGA-AC-A8OQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EVI5

insertion

Nonsense_Mutation

novel

c.1736_1737insATCCCTGGCCTCTACCCACTAGATGCCAGTAACGGCTCTCCTACCT

p.Ile580SerfsTer7

p.I580Sfs*7

O60447

protein_coding

TCGA-AN-A041-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

EVI5

deletion

Frame_Shift_Del

novel

c.902delA

p.His301LeufsTer25

p.H301Lfs*25

O60447

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

EVI5

SNV

Missense_Mutation

rs771345036

c.2003G>A

p.Ser668Asn

p.S668N

O60447

protein_coding

tolerated(0.27)

benign(0.018)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

EVI5

SNV

Missense_Mutation

novel

c.1425G>T

p.Glu475Asp

p.E475D

O60447

protein_coding

deleterious(0.03)

possibly_damaging(0.669)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

EVI5

SNV

Missense_Mutation

novel

c.675G>T

p.Glu225Asp

p.E225D

O60447

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

EVI5

SNV

Missense_Mutation

c.2441G>C

p.Arg814Thr

p.R814T

O60447

protein_coding

tolerated_low_confidence(0.6)

benign(0.017)

TCGA-EK-A2IP-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

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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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