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: VPS13C

Gene summary for VPS13C

Gene summary.

Gene information	Species	Human
	Gene symbol	VPS13C
	Gene ID	54832
	Gene name	vacuolar protein sorting 13 homolog C
	Gene Alias	PARK23
	Cytomap	15q22.2
	Gene Type	protein-coding
	GO ID	GO:0000422
	UniProtAcc	Q709C8

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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
54832	VPS13C	052097_1595-all-cells	Human	Prostate	BPH	5.15e-18	4.66e-01	0.0972
54832	VPS13C	052099_1652-all-cells	Human	Prostate	BPH	9.33e-11	3.40e-01	0.1038
54832	VPS13C	Dong_P1	Human	Prostate	Tumor	1.63e-11	1.03e-01	0.035
54832	VPS13C	Dong_P3	Human	Prostate	Tumor	8.71e-17	1.93e-01	0.0278
54832	VPS13C	Dong_P4	Human	Prostate	Tumor	8.50e-10	2.95e-01	0.0292
54832	VPS13C	Dong_P5	Human	Prostate	Tumor	1.43e-11	-4.00e-02	0.053
54832	VPS13C	GSM5353215_PA_AUG_PB_1B_S2	Human	Prostate	Tumor	8.92e-03	6.45e-01	0.1557
54832	VPS13C	GSM5353216_PA_PB1A_Pool_1_3_S50_L002	Human	Prostate	Tumor	1.35e-05	7.71e-01	0.159
54832	VPS13C	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	2.31e-27	9.99e-01	0.1633
54832	VPS13C	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	2.22e-20	7.74e-01	0.1608
54832	VPS13C	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	2.70e-08	6.30e-01	0.1604
54832	VPS13C	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	1.29e-10	6.57e-01	0.1621
54832	VPS13C	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	4.65e-10	7.72e-01	0.1619
54832	VPS13C	GSM5353226_PA_PR5196-2_Pool_1_2_3_S54_L002	Human	Prostate	Tumor	3.47e-06	7.79e-01	0.159
54832	VPS13C	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	2.89e-06	5.32e-01	0.1602
54832	VPS13C	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	8.87e-03	5.03e-01	0.1608
54832	VPS13C	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	4.38e-06	4.12e-01	0.1575
54832	VPS13C	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	3.55e-04	3.48e-01	0.1545
54832	VPS13C	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	1.98e-05	4.03e-01	0.1569
54832	VPS13C	male-WTA	Human	Thyroid	PTC	2.34e-29	2.95e-01	0.1037

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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
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:0072594	Colorectum	AD	establishment of protein localization to organelle	148/3918	422/18723	7.95e-12	1.04e-09	148
GO:0048193	Colorectum	AD	Golgi vesicle transport	109/3918	296/18723	1.80e-10	1.68e-08	109
GO:0022411	Colorectum	AD	cellular component disassembly	147/3918	443/18723	8.53e-10	6.76e-08	147
GO:0010506	Colorectum	AD	regulation of autophagy	111/3918	317/18723	3.57e-09	2.35e-07	111
GO:0016482	Colorectum	AD	cytosolic transport	68/3918	168/18723	6.00e-09	3.72e-07	68
GO:0016236	Colorectum	AD	macroautophagy	103/3918	291/18723	6.76e-09	4.15e-07	103
GO:0006605	Colorectum	AD	protein targeting	105/3918	314/18723	1.39e-07	6.44e-06	105
GO:0032868	Colorectum	AD	response to insulin	91/3918	264/18723	2.02e-07	8.48e-06	91
GO:0006892	Colorectum	AD	post-Golgi vesicle-mediated transport	45/3918	104/18723	2.22e-07	9.26e-06	45
GO:0010821	Colorectum	AD	regulation of mitochondrion organization	57/3918	144/18723	2.43e-07	9.92e-06	57
GO:0007034	Colorectum	AD	vacuolar transport	60/3918	157/18723	4.97e-07	1.85e-05	60
GO:1903008	Colorectum	AD	organelle disassembly	46/3918	114/18723	1.81e-06	5.48e-05	46
GO:0043434	Colorectum	AD	response to peptide hormone	126/3918	414/18723	2.70e-06	7.86e-05	126
GO:1903146	Colorectum	AD	regulation of autophagy of mitochondrion	19/3918	33/18723	4.52e-06	1.21e-04	19
GO:0000422	Colorectum	AD	autophagy of mitochondrion	35/3918	81/18723	4.94e-06	1.29e-04	35
GO:0061726	Colorectum	AD	mitochondrion disassembly	35/3918	81/18723	4.94e-06	1.29e-04	35
GO:0061912	Colorectum	AD	selective autophagy	29/3918	68/18723	4.20e-05	7.39e-04	29
GO:0016241	Colorectum	AD	regulation of macroautophagy	50/3918	141/18723	4.55e-05	7.92e-04	50
GO:0072665	Colorectum	AD	protein localization to vacuole	27/3918	67/18723	2.40e-04	3.04e-03	27
GO:0000423	Colorectum	AD	mitophagy	14/3918	28/18723	6.01e-04	6.33e-03	14

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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

VPS13C

SNV

Missense_Mutation

c.10711N>A

p.Val3571Ile

p.V3571I

Q709C8

protein_coding

tolerated(1)

benign(0.015)

TCGA-A2-A0EU-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

VPS13C

SNV

Missense_Mutation

c.4351N>A

p.Glu1451Lys

p.E1451K

Q709C8

protein_coding

tolerated(0.55)

benign(0.003)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

VPS13C

SNV

Missense_Mutation

rs150119821

c.11150C>A

p.Ala3717Asp

p.A3717D

Q709C8

protein_coding

tolerated(0.63)

benign(0)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

VPS13C

SNV

Missense_Mutation

c.2519C>A

p.Ala840Asp

p.A840D

Q709C8

protein_coding

tolerated(0.29)

benign(0)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

VPS13C

SNV

Missense_Mutation

novel

c.6325N>C

p.Ile2109Leu

p.I2109L

Q709C8

protein_coding

deleterious(0.03)

benign(0.015)

TCGA-A2-A3XX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

VPS13C

SNV

Missense_Mutation

novel

c.6324N>T

p.Met2108Ile

p.M2108I

Q709C8

protein_coding

tolerated(0.36)

benign(0.001)

TCGA-A2-A3XX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

VPS13C

SNV

Missense_Mutation

c.4537N>T

p.Ala1513Ser

p.A1513S

Q709C8

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

VPS13C

SNV

Missense_Mutation

c.436N>C

p.Asp146His

p.D146H

Q709C8

protein_coding

deleterious(0.02)

possibly_damaging(0.533)

TCGA-A8-A0A2-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

VPS13C

SNV

Missense_Mutation

c.7222G>C

p.Glu2408Gln

p.E2408Q

Q709C8

protein_coding

deleterious(0.01)

possibly_damaging(0.766)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

VPS13C

SNV

Missense_Mutation

novel

c.5620G>C

p.Asp1874His

p.D1874H

Q709C8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

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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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