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	A015-C-204	Human	Colorectum	FAP	5.03e-08	-4.12e-01	-0.0228
7813	EVI5	A014-C-040	Human	Colorectum	FAP	9.32e-09	-6.33e-01	-0.1184
7813	EVI5	A002-C-201	Human	Colorectum	FAP	2.51e-15	-3.83e-01	0.0324
7813	EVI5	A001-C-119	Human	Colorectum	FAP	2.44e-09	-5.01e-01	-0.1557
7813	EVI5	A001-C-108	Human	Colorectum	FAP	8.52e-17	-3.68e-01	-0.0272
7813	EVI5	A002-C-205	Human	Colorectum	FAP	9.28e-25	-4.08e-01	-0.1236
7813	EVI5	A015-C-005	Human	Colorectum	FAP	3.55e-03	-2.62e-01	-0.0336
7813	EVI5	A015-C-006	Human	Colorectum	FAP	6.56e-21	-5.10e-01	-0.0994
7813	EVI5	A015-C-106	Human	Colorectum	FAP	6.23e-13	-3.76e-01	-0.0511
7813	EVI5	A002-C-114	Human	Colorectum	FAP	6.50e-24	-4.28e-01	-0.1561
7813	EVI5	A015-C-104	Human	Colorectum	FAP	1.77e-36	-6.23e-01	-0.1899
7813	EVI5	A001-C-014	Human	Colorectum	FAP	2.37e-17	-3.53e-01	0.0135
7813	EVI5	A002-C-016	Human	Colorectum	FAP	4.65e-24	-3.48e-01	0.0521
7813	EVI5	A015-C-002	Human	Colorectum	FAP	1.56e-14	-4.04e-01	-0.0763
7813	EVI5	A001-C-203	Human	Colorectum	FAP	1.15e-12	-3.56e-01	-0.0481
7813	EVI5	A002-C-116	Human	Colorectum	FAP	6.77e-39	-5.11e-01	-0.0452
7813	EVI5	A014-C-008	Human	Colorectum	FAP	1.95e-17	-3.37e-01	-0.191
7813	EVI5	A018-E-020	Human	Colorectum	FAP	2.74e-24	-4.64e-01	-0.2034
7813	EVI5	F034	Human	Colorectum	FAP	2.20e-25	-4.78e-01	-0.0665
7813	EVI5	F072B	Human	Colorectum	FAP	3.43e-02	-2.09e-01	0.257

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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:00430877	Cervix	CC	regulation of GTPase activity	79/2311	348/18723	4.21e-08	2.60e-06	79
GO:00435476	Cervix	CC	positive regulation of GTPase activity	53/2311	255/18723	8.72e-05	1.16e-03	53
GO:00161977	Cervix	CC	endosomal transport	48/2311	230/18723	1.65e-04	1.97e-03	48
GO:00164827	Cervix	CC	cytosolic transport	33/2311	168/18723	4.43e-03	2.70e-02	33
GO:0016197	Colorectum	AD	endosomal transport	90/3918	230/18723	1.88e-10	1.73e-08	90
GO:0016482	Colorectum	AD	cytosolic transport	68/3918	168/18723	6.00e-09	3.72e-07	68
GO:0043087	Colorectum	AD	regulation of GTPase activity	110/3918	348/18723	1.64e-06	5.03e-05	110
GO:0042147	Colorectum	AD	retrograde transport, endosome to Golgi	37/3918	91/18723	1.46e-05	3.14e-04	37
GO:0043547	Colorectum	AD	positive regulation of GTPase activity	75/3918	255/18723	7.95e-04	7.91e-03	75
GO:00161971	Colorectum	SER	endosomal transport	61/2897	230/18723	1.03e-05	3.35e-04	61
GO:00164821	Colorectum	SER	cytosolic transport	46/2897	168/18723	5.20e-05	1.25e-03	46
GO:00430871	Colorectum	SER	regulation of GTPase activity	77/2897	348/18723	5.90e-04	8.07e-03	77
GO:00161972	Colorectum	MSS	endosomal transport	79/3467	230/18723	7.04e-09	4.39e-07	79
GO:00164822	Colorectum	MSS	cytosolic transport	59/3467	168/18723	2.29e-07	9.79e-06	59
GO:00430872	Colorectum	MSS	regulation of GTPase activity	101/3467	348/18723	1.00e-06	3.46e-05	101
GO:00421471	Colorectum	MSS	retrograde transport, endosome to Golgi	33/3467	91/18723	4.78e-05	8.71e-04	33
GO:00435471	Colorectum	MSS	positive regulation of GTPase activity	68/3467	255/18723	7.97e-04	8.38e-03	68
GO:00430873	Colorectum	FAP	regulation of GTPase activity	85/2622	348/18723	1.20e-07	7.68e-06	85
GO:00164823	Colorectum	FAP	cytosolic transport	47/2622	168/18723	1.58e-06	6.72e-05	47
GO:00435472	Colorectum	FAP	positive regulation of GTPase activity	61/2622	255/18723	1.39e-05	3.73e-04	61

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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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