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: VIM

Gene summary for VIM

Gene summary.

Gene information	Species	Human
	Gene symbol	VIM
	Gene ID	7431
	Gene name	vimentin
	Gene Alias	VIM
	Cytomap	10p13
	Gene Type	protein-coding
	GO ID	GO:0001654
	UniProtAcc	P08670

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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
7431	VIM	GSM4909281	Human	Breast	IDC	2.52e-46	1.02e+00	0.21
7431	VIM	GSM4909285	Human	Breast	IDC	1.17e-70	1.12e+00	0.21
7431	VIM	GSM4909286	Human	Breast	IDC	2.72e-68	1.04e+00	0.1081
7431	VIM	GSM4909287	Human	Breast	IDC	3.96e-02	3.75e-01	0.2057
7431	VIM	GSM4909290	Human	Breast	IDC	4.93e-07	-4.84e-01	0.2096
7431	VIM	GSM4909293	Human	Breast	IDC	1.42e-04	-3.92e-01	0.1581
7431	VIM	GSM4909294	Human	Breast	IDC	1.30e-07	-3.66e-01	0.2022
7431	VIM	GSM4909295	Human	Breast	IDC	3.61e-04	5.43e-01	0.0898
7431	VIM	GSM4909296	Human	Breast	IDC	5.33e-13	-5.37e-01	0.1524
7431	VIM	GSM4909297	Human	Breast	IDC	1.01e-02	3.75e-04	0.1517
7431	VIM	GSM4909298	Human	Breast	IDC	3.88e-03	2.78e-02	0.1551
7431	VIM	GSM4909299	Human	Breast	IDC	8.43e-21	6.93e-01	0.035
7431	VIM	GSM4909301	Human	Breast	IDC	4.45e-15	-5.36e-01	0.1577
7431	VIM	GSM4909304	Human	Breast	IDC	1.96e-15	-5.28e-01	0.1636
7431	VIM	GSM4909307	Human	Breast	IDC	1.01e-02	-3.20e-01	0.1569
7431	VIM	GSM4909308	Human	Breast	IDC	4.81e-09	-4.89e-01	0.158
7431	VIM	GSM4909311	Human	Breast	IDC	7.66e-18	-5.34e-01	0.1534
7431	VIM	GSM4909312	Human	Breast	IDC	3.27e-25	-5.95e-01	0.1552
7431	VIM	GSM4909315	Human	Breast	IDC	1.61e-37	9.49e-01	0.21
7431	VIM	GSM4909319	Human	Breast	IDC	6.17e-21	-5.41e-01	0.1563

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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
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:00457279	Breast	Precancer	positive regulation of translation	32/1080	136/18723	5.89e-12	9.27e-10	32
GO:00342509	Breast	Precancer	positive regulation of cellular amide metabolic process	33/1080	162/18723	1.72e-10	1.77e-08	33
GO:19033118	Breast	Precancer	regulation of mRNA metabolic process	38/1080	288/18723	1.63e-06	5.97e-05	38
GO:00022378	Breast	Precancer	response to molecule of bacterial origin	43/1080	363/18723	6.05e-06	1.72e-04	43
GO:00324968	Breast	Precancer	response to lipopolysaccharide	41/1080	343/18723	7.94e-06	2.17e-04	41
GO:00064028	Breast	Precancer	mRNA catabolic process	31/1080	232/18723	1.12e-05	2.93e-04	31
GO:00064018	Breast	Precancer	RNA catabolic process	34/1080	278/18723	2.88e-05	6.39e-04	34
GO:0045104	Breast	Precancer	intermediate filament cytoskeleton organization	11/1080	51/18723	1.26e-04	2.22e-03	11
GO:0045103	Breast	Precancer	intermediate filament-based process	11/1080	52/18723	1.52e-04	2.60e-03	11
GO:00346558	Breast	Precancer	nucleobase-containing compound catabolic process	42/1080	407/18723	1.91e-04	3.06e-03	42
GO:00420633	Breast	Precancer	gliogenesis	33/1080	301/18723	3.06e-04	4.40e-03	33
GO:00467007	Breast	Precancer	heterocycle catabolic process	44/1080	445/18723	3.49e-04	4.88e-03	44
GO:00712227	Breast	Precancer	cellular response to lipopolysaccharide	25/1080	209/18723	4.41e-04	5.85e-03	25
GO:00442708	Breast	Precancer	cellular nitrogen compound catabolic process	44/1080	451/18723	4.64e-04	6.12e-03	44
GO:00712167	Breast	Precancer	cellular response to biotic stimulus	28/1080	246/18723	4.67e-04	6.14e-03	28
GO:00194397	Breast	Precancer	aromatic compound catabolic process	44/1080	467/18723	9.55e-04	1.07e-02	44
GO:00712197	Breast	Precancer	cellular response to molecule of bacterial origin	25/1080	221/18723	1.00e-03	1.12e-02	25
GO:00100013	Breast	Precancer	glial cell differentiation	25/1080	225/18723	1.29e-03	1.37e-02	25
GO:19013617	Breast	Precancer	organic cyclic compound catabolic process	45/1080	495/18723	1.73e-03	1.74e-02	45

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516918	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa0516919	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa0516922	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0516932	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0516941	Breast	DCIS	Epstein-Barr virus infection	46/846	202/8465	5.60e-08	1.13e-06	8.33e-07	46
hsa0516951	Breast	DCIS	Epstein-Barr virus infection	46/846	202/8465	5.60e-08	1.13e-06	8.33e-07	46
hsa0516920	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa05169110	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa0516924	Endometrium	AEH	Epstein-Barr virus infection	42/1197	202/8465	5.72e-03	3.05e-02	2.23e-02	42
hsa05169111	Endometrium	AEH	Epstein-Barr virus infection	42/1197	202/8465	5.72e-03	3.05e-02	2.23e-02	42
hsa0516925	Endometrium	EEC	Epstein-Barr virus infection	47/1237	202/8465	6.17e-04	4.41e-03	3.29e-03	47
hsa0516934	Endometrium	EEC	Epstein-Barr virus infection	47/1237	202/8465	6.17e-04	4.41e-03	3.29e-03	47
hsa0516930	Esophagus	HGIN	Epstein-Barr virus infection	55/1383	202/8465	5.13e-05	6.19e-04	4.92e-04	55
hsa05169114	Esophagus	HGIN	Epstein-Barr virus infection	55/1383	202/8465	5.13e-05	6.19e-04	4.92e-04	55
hsa05169210	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa0516937	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa0516914	Liver	Cirrhotic	Epstein-Barr virus infection	80/2530	202/8465	1.80e-03	8.33e-03	5.13e-03	80
hsa0516915	Liver	Cirrhotic	Epstein-Barr virus infection	80/2530	202/8465	1.80e-03	8.33e-03	5.13e-03	80
hsa0516921	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128
hsa0516931	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128

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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

VIM

SNV

Missense_Mutation

c.585N>C

p.Gln195His

p.Q195H

P08670

protein_coding

tolerated(0.54)

possibly_damaging(0.774)

TCGA-A7-A26H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

VIM

SNV

Missense_Mutation

c.661G>A

p.Glu221Lys

p.E221K

P08670

protein_coding

deleterious(0.01)

possibly_damaging(0.867)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

VIM

SNV

Missense_Mutation

novel

c.406G>C

p.Glu136Gln

p.E136Q

P08670

protein_coding

tolerated(0.28)

probably_damaging(0.954)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

VIM

SNV

Missense_Mutation

c.1349N>C

p.Arg450Thr

p.R450T

P08670

protein_coding

deleterious(0)

possibly_damaging(0.703)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

VIM

insertion

In_Frame_Ins

novel

c.577_578insGGGGCGGGGATGGCGGGGCTGTCC

p.Met193delinsArgGlyGlyAspGlyGlyAlaValLeu

p.M193delinsRGGDGGAVL

P08670

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

VIM

SNV

Missense_Mutation

c.459N>C

p.Glu153Asp

p.E153D

P08670

protein_coding

deleterious(0.01)

possibly_damaging(0.472)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

VIM

SNV

Missense_Mutation

rs376668602

c.1369N>A

p.Glu457Lys

p.E457K

P08670

protein_coding

deleterious(0)

possibly_damaging(0.877)

TCGA-VS-A8QC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

paclitaxel

VIM

SNV

Missense_Mutation

rs373859810

c.1230N>C

p.Arg410Ser

p.R410S

P08670

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AA-3950-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

VIM

SNV

Missense_Mutation

c.628N>A

p.Val210Ile

p.V210I

P08670

protein_coding

deleterious(0)

possibly_damaging(0.631)

TCGA-AA-A02K-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folinic

VIM

SNV

Missense_Mutation

c.211C>T

p.Arg71Trp

p.R71W

P08670

protein_coding

tolerated(0.1)

probably_damaging(0.93)

TCGA-AD-5900-01

Colorectum

colon adenocarcinoma

Male

>=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
7431	VIM	DRUGGABLE GENOME		ENU		3440878
7431	VIM	DRUGGABLE GENOME		GANGLIOSIDE GM2		7923401
7431	VIM	DRUGGABLE GENOME		CHEMBL2108045	PRITUMUMAB
7431	VIM	DRUGGABLE GENOME		GELDANAMYCIN	GELDANAMYCIN	16328963
7431	VIM	DRUGGABLE GENOME		DIMETHYL SULFOXIDE		6376521
7431	VIM	DRUGGABLE GENOME		IL-2	ALDESLEUKIN	7691937

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