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: SVIL

Gene summary for SVIL

Gene summary.

Gene information	Species	Human
	Gene symbol	SVIL
	Gene ID	6840
	Gene name	supervillin
	Gene Alias	MFM10
	Cytomap	10p11.23
	Gene Type	protein-coding
	GO ID	GO:0000910
	UniProtAcc	O95425

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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
6840	SVIL	CA_HPV_1	Human	Cervix	CC	1.60e-04	-2.80e-01	0.0264
6840	SVIL	CA_HPV_3	Human	Cervix	CC	5.31e-16	4.54e-01	0.0414
6840	SVIL	CCI_1	Human	Cervix	CC	6.99e-08	1.45e+00	0.528
6840	SVIL	CCI_2	Human	Cervix	CC	9.73e-16	2.21e+00	0.5249
6840	SVIL	CCI_3	Human	Cervix	CC	2.90e-09	1.28e+00	0.516
6840	SVIL	sample3	Human	Cervix	CC	8.16e-04	1.09e-01	0.1387
6840	SVIL	HTA11_3410_2000001011	Human	Colorectum	AD	9.47e-24	-6.87e-01	0.0155
6840	SVIL	HTA11_2487_2000001011	Human	Colorectum	SER	3.29e-02	-3.44e-01	-0.1808
6840	SVIL	HTA11_2951_2000001011	Human	Colorectum	AD	3.02e-04	-8.22e-01	0.0216
6840	SVIL	HTA11_347_2000001011	Human	Colorectum	AD	1.76e-11	5.75e-01	-0.1954
6840	SVIL	HTA11_3361_2000001011	Human	Colorectum	AD	1.75e-05	-5.00e-01	-0.1207
6840	SVIL	HTA11_9341_2000001011	Human	Colorectum	SER	3.11e-06	-6.27e-01	-0.00410000000000005
6840	SVIL	HTA11_866_3004761011	Human	Colorectum	AD	4.05e-12	-6.72e-01	0.096
6840	SVIL	HTA11_4255_2000001011	Human	Colorectum	SER	1.07e-03	-5.71e-01	0.0446
6840	SVIL	HTA11_8622_2000001021	Human	Colorectum	SER	1.41e-07	-7.78e-01	0.0528
6840	SVIL	HTA11_6818_2000001011	Human	Colorectum	AD	1.14e-03	-4.23e-01	0.0112
6840	SVIL	HTA11_7469_2000001011	Human	Colorectum	AD	2.14e-03	-4.88e-01	-0.0124
6840	SVIL	HTA11_99999970781_79442	Human	Colorectum	MSS	8.01e-29	-5.96e-01	0.294
6840	SVIL	HTA11_99999971662_82457	Human	Colorectum	MSS	3.09e-55	-1.02e+00	0.3859
6840	SVIL	HTA11_99999973899_84307	Human	Colorectum	MSS	2.62e-03	-6.70e-01	0.2585

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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
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:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:003297010	Cervix	CC	regulation of actin filament-based process	96/2311	397/18723	4.00e-11	8.54e-09	96
GO:190290310	Cervix	CC	regulation of supramolecular fiber organization	92/2311	383/18723	1.49e-10	2.48e-08	92
GO:003295610	Cervix	CC	regulation of actin cytoskeleton organization	86/2311	358/18723	5.90e-10	7.51e-08	86
GO:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:011005310	Cervix	CC	regulation of actin filament organization	67/2311	278/18723	4.01e-08	2.54e-06	67
GO:005125810	Cervix	CC	protein polymerization	70/2311	297/18723	5.20e-08	3.11e-06	70
GO:003227110	Cervix	CC	regulation of protein polymerization	57/2311	233/18723	2.37e-07	1.03e-05	57
GO:00081549	Cervix	CC	actin polymerization or depolymerization	51/2311	218/18723	4.05e-06	1.05e-04	51
GO:00457876	Cervix	CC	positive regulation of cell cycle	66/2311	313/18723	7.78e-06	1.81e-04	66
GO:00300419	Cervix	CC	actin filament polymerization	45/2311	191/18723	1.20e-05	2.54e-04	45
GO:00325359	Cervix	CC	regulation of cellular component size	76/2311	383/18723	1.66e-05	3.21e-04	76
GO:19029048	Cervix	CC	negative regulation of supramolecular fiber organization	40/2311	167/18723	2.39e-05	4.17e-04	40
GO:00313339	Cervix	CC	negative regulation of protein-containing complex assembly	35/2311	141/18723	3.41e-05	5.55e-04	35
GO:00308339	Cervix	CC	regulation of actin filament polymerization	40/2311	172/18723	4.90e-05	7.40e-04	40
GO:002241110	Cervix	CC	cellular component disassembly	83/2311	443/18723	6.04e-05	8.68e-04	83
GO:00106399	Cervix	CC	negative regulation of organelle organization	68/2311	348/18723	7.40e-05	1.03e-03	68
GO:00900685	Cervix	CC	positive regulation of cell cycle process	50/2311	236/18723	8.25e-05	1.11e-03	50
GO:00080649	Cervix	CC	regulation of actin polymerization or depolymerization	42/2311	188/18723	8.60e-05	1.15e-03	42
GO:00605375	Cervix	CC	muscle tissue development	76/2311	403/18723	9.76e-05	1.27e-03	76

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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

SVIL

SNV

Missense_Mutation

novel

c.2392N>A

p.Glu798Lys

p.E798K

O95425

protein_coding

deleterious(0)

benign(0.437)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

SVIL

SNV

Missense_Mutation

rs767857736

c.5821G>T

p.Ala1941Ser

p.A1941S

O95425

protein_coding

deleterious(0)

possibly_damaging(0.593)

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

SVIL

SNV

Missense_Mutation

c.2546G>A

p.Arg849His

p.R849H

O95425

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-A8-A08X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

SVIL

SNV

Missense_Mutation

c.6439G>C

p.Asp2147His

p.D2147H

O95425

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SVIL

SNV

Missense_Mutation

novel

c.3195N>T

p.Gln1065His

p.Q1065H

O95425

protein_coding

tolerated_low_confidence(0.19)

benign(0.336)

TCGA-AC-A8OP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SVIL

SNV

Missense_Mutation

novel

c.4578N>A

p.His1526Gln

p.H1526Q

O95425

protein_coding

tolerated(0.31)

benign(0.017)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SVIL

SNV

Missense_Mutation

rs745851162

c.2753N>T

p.Ser918Leu

p.S918L

O95425

protein_coding

tolerated_low_confidence(0.11)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SVIL

SNV

Missense_Mutation

novel

c.4166A>G

p.Glu1389Gly

p.E1389G

O95425

protein_coding

deleterious(0)

probably_damaging(0.968)

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

SVIL

SNV

Missense_Mutation

rs777510006

c.2684N>A

p.Arg895His

p.R895H

O95425

protein_coding

tolerated_low_confidence(0.6)

benign(0.003)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

SVIL

SNV

Missense_Mutation

novel

c.6376G>A

p.Glu2126Lys

p.E2126K

O95425

protein_coding

deleterious(0.05)

benign(0.118)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

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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