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: VAPB

Gene summary for VAPB

Gene summary.

Gene information	Species	Human
	Gene symbol	VAPB
	Gene ID	9217
	Gene name	VAMP associated protein B and C
	Gene Alias	ALS8
	Cytomap	20q13.32
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	O95292

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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
9217	VAPB	LZE4T	Human	Esophagus	ESCC	1.38e-10	2.95e-01	0.0811
9217	VAPB	LZE7T	Human	Esophagus	ESCC	1.39e-09	2.32e-01	0.0667
9217	VAPB	LZE20T	Human	Esophagus	ESCC	3.54e-09	2.68e-01	0.0662
9217	VAPB	LZE24T	Human	Esophagus	ESCC	4.02e-19	3.65e-01	0.0596
9217	VAPB	P1T-E	Human	Esophagus	ESCC	1.42e-11	4.53e-01	0.0875
9217	VAPB	P2T-E	Human	Esophagus	ESCC	9.55e-31	6.58e-01	0.1177
9217	VAPB	P4T-E	Human	Esophagus	ESCC	1.09e-15	2.19e-01	0.1323
9217	VAPB	P5T-E	Human	Esophagus	ESCC	1.47e-11	2.71e-01	0.1327
9217	VAPB	P8T-E	Human	Esophagus	ESCC	9.68e-15	1.87e-01	0.0889
9217	VAPB	P9T-E	Human	Esophagus	ESCC	1.08e-06	2.59e-01	0.1131
9217	VAPB	P10T-E	Human	Esophagus	ESCC	6.82e-73	1.17e+00	0.116
9217	VAPB	P11T-E	Human	Esophagus	ESCC	4.05e-17	6.44e-01	0.1426
9217	VAPB	P12T-E	Human	Esophagus	ESCC	1.93e-29	7.18e-01	0.1122
9217	VAPB	P15T-E	Human	Esophagus	ESCC	1.90e-40	7.63e-01	0.1149
9217	VAPB	P16T-E	Human	Esophagus	ESCC	1.67e-48	8.53e-01	0.1153
9217	VAPB	P17T-E	Human	Esophagus	ESCC	3.80e-08	4.19e-01	0.1278
9217	VAPB	P19T-E	Human	Esophagus	ESCC	5.14e-06	7.10e-01	0.1662
9217	VAPB	P20T-E	Human	Esophagus	ESCC	7.82e-38	7.07e-01	0.1124
9217	VAPB	P21T-E	Human	Esophagus	ESCC	1.25e-24	5.94e-01	0.1617
9217	VAPB	P22T-E	Human	Esophagus	ESCC	1.55e-23	4.34e-01	0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:004819318	Esophagus	ESCC	Golgi vesicle transport	231/8552	296/18723	1.82e-30	9.63e-28	231
GO:0016032111	Esophagus	ESCC	viral process	301/8552	415/18723	3.34e-29	1.32e-26	301
GO:0034976111	Esophagus	ESCC	response to endoplasmic reticulum stress	192/8552	256/18723	7.15e-22	1.30e-19	192
GO:0019058111	Esophagus	ESCC	viral life cycle	226/8552	317/18723	1.17e-20	1.76e-18	226
GO:001605014	Esophagus	ESCC	vesicle organization	211/8552	300/18723	2.85e-18	2.87e-16	211
GO:0035966111	Esophagus	ESCC	response to topologically incorrect protein	125/8552	159/18723	1.44e-17	1.27e-15	125
GO:0006986111	Esophagus	ESCC	response to unfolded protein	107/8552	137/18723	7.01e-15	3.87e-13	107
GO:000688815	Esophagus	ESCC	endoplasmic reticulum to Golgi vesicle-mediated transport	102/8552	130/18723	1.73e-14	9.22e-13	102
GO:0019079111	Esophagus	ESCC	viral genome replication	102/8552	131/18723	4.31e-14	2.19e-12	102
GO:0035967111	Esophagus	ESCC	cellular response to topologically incorrect protein	90/8552	116/18723	1.94e-12	8.11e-11	90
GO:0050792111	Esophagus	ESCC	regulation of viral process	119/8552	164/18723	2.19e-12	9.03e-11	119
GO:0006900111	Esophagus	ESCC	vesicle budding from membrane	54/8552	61/18723	2.66e-12	1.07e-10	54
GO:1903900111	Esophagus	ESCC	regulation of viral life cycle	106/8552	148/18723	1.26e-10	3.72e-09	106
GO:0044403111	Esophagus	ESCC	biological process involved in symbiotic interaction	186/8552	290/18723	1.43e-10	4.16e-09	186
GO:0034620111	Esophagus	ESCC	cellular response to unfolded protein	74/8552	96/18723	3.10e-10	8.66e-09	74
GO:0045069110	Esophagus	ESCC	regulation of viral genome replication	67/8552	85/18723	3.81e-10	1.04e-08	67
GO:0051701111	Esophagus	ESCC	biological process involved in interaction with host	135/8552	203/18723	1.49e-09	3.49e-08	135
GO:003096818	Esophagus	ESCC	endoplasmic reticulum unfolded protein response	59/8552	74/18723	1.90e-09	4.36e-08	59
GO:0048524110	Esophagus	ESCC	positive regulation of viral process	52/8552	65/18723	1.41e-08	2.77e-07	52
GO:000702914	Esophagus	ESCC	endoplasmic reticulum organization	65/8552	87/18723	3.28e-08	6.08e-07	65

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05014210	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa05022210	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa0501438	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0502238	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa0501414	Liver	Cirrhotic	Amyotrophic lateral sclerosis	187/2530	364/8465	1.56e-18	6.50e-17	4.01e-17	187
hsa0502214	Liver	Cirrhotic	Pathways of neurodegeneration - multiple diseases	217/2530	476/8465	7.30e-14	2.03e-12	1.25e-12	217
hsa049792	Liver	Cirrhotic	Cholesterol metabolism	30/2530	51/8465	1.59e-05	1.39e-04	8.60e-05	30
hsa0501415	Liver	Cirrhotic	Amyotrophic lateral sclerosis	187/2530	364/8465	1.56e-18	6.50e-17	4.01e-17	187
hsa0502215	Liver	Cirrhotic	Pathways of neurodegeneration - multiple diseases	217/2530	476/8465	7.30e-14	2.03e-12	1.25e-12	217
hsa049793	Liver	Cirrhotic	Cholesterol metabolism	30/2530	51/8465	1.59e-05	1.39e-04	8.60e-05	30
hsa0501422	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa0502222	Liver	HCC	Pathways of neurodegeneration - multiple diseases	298/4020	476/8465	6.59e-12	1.30e-10	7.22e-11	298
hsa049794	Liver	HCC	Cholesterol metabolism	41/4020	51/8465	1.33e-06	1.35e-05	7.49e-06	41
hsa0501432	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa0502232	Liver	HCC	Pathways of neurodegeneration - multiple diseases	298/4020	476/8465	6.59e-12	1.30e-10	7.22e-11	298
hsa049795	Liver	HCC	Cholesterol metabolism	41/4020	51/8465	1.33e-06	1.35e-05	7.49e-06	41
hsa0501428	Oral cavity	OSCC	Amyotrophic lateral sclerosis	246/3704	364/8465	6.65e-21	1.11e-18	5.67e-19	246
hsa0502228	Oral cavity	OSCC	Pathways of neurodegeneration - multiple diseases	292/3704	476/8465	1.60e-15	4.47e-14	2.28e-14	292
hsa05014112	Oral cavity	OSCC	Amyotrophic lateral sclerosis	246/3704	364/8465	6.65e-21	1.11e-18	5.67e-19	246
hsa05022112	Oral cavity	OSCC	Pathways of neurodegeneration - multiple diseases	292/3704	476/8465	1.60e-15	4.47e-14	2.28e-14	292

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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

VAPB

SNV

Missense_Mutation

c.441G>C

p.Lys147Asn

p.K147N

O95292

protein_coding

tolerated(0.08)

probably_damaging(0.994)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

VAPB

SNV

Missense_Mutation

novel

c.88N>G

p.Leu30Val

p.L30V

O95292

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AC-A6IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

VAPB

insertion

Nonsense_Mutation

novel

c.385_386insCAATGCATGGTTAGGTCTCAGTGGACTTTCTCTGTTCCC

p.Asn129delinsThrMetHisGlyTerValSerValAspPheLeuCysSerHis

p.N129delinsTMHG*VSVDFLCSH

O95292

protein_coding

TCGA-A2-A0EM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

VAPB

SNV

Missense_Mutation

novel

c.142N>T

p.Ala48Ser

p.A48S

O95292

protein_coding

deleterious(0)

possibly_damaging(0.729)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

VAPB

SNV

Missense_Mutation

novel

c.404N>C

p.Val135Ala

p.V135A

O95292

protein_coding

tolerated(0.25)

benign(0.003)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

VAPB

SNV

Missense_Mutation

c.487N>A

p.Asp163Asn

p.D163N

O95292

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-QG-A5Z2-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

VAPB

SNV

Missense_Mutation

novel

c.340N>A

p.Leu114Ile

p.L114I

O95292

protein_coding

tolerated(0.12)

probably_damaging(0.99)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

VAPB

SNV

Missense_Mutation

novel

c.329A>C

p.Lys110Thr

p.K110T

O95292

protein_coding

tolerated(0.05)

probably_damaging(0.998)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

VAPB

SNV

Missense_Mutation

rs149215094

c.700N>A

p.Val234Ile

p.V234I

O95292

protein_coding

tolerated(0.88)

benign(0.003)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

VAPB

SNV

Missense_Mutation

c.151N>G

p.Arg51Gly

p.R51G

O95292

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid 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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