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: VKORC1L1

Gene summary for VKORC1L1

Gene summary.

Gene information	Species	Human
	Gene symbol	VKORC1L1
	Gene ID	154807
	Gene name	vitamin K epoxide reductase complex subunit 1 like 1
	Gene Alias	VKORC1L1
	Cytomap	7q11.21
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q8N0U8

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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
154807	VKORC1L1	HCC1_Meng	Human	Liver	HCC	1.15e-70	3.29e-02	0.0246
154807	VKORC1L1	HCC2_Meng	Human	Liver	HCC	3.62e-31	7.54e-02	0.0107
154807	VKORC1L1	cirrhotic2	Human	Liver	Cirrhotic	3.13e-02	-6.98e-02	0.0201
154807	VKORC1L1	HCC1	Human	Liver	HCC	2.11e-06	3.38e+00	0.5336
154807	VKORC1L1	HCC2	Human	Liver	HCC	1.69e-12	2.47e+00	0.5341
154807	VKORC1L1	HCC5	Human	Liver	HCC	1.01e-02	9.25e-01	0.4932
154807	VKORC1L1	Pt13.a	Human	Liver	HCC	4.62e-02	-1.45e-01	0.021
154807	VKORC1L1	S015	Human	Liver	HCC	1.11e-02	4.11e-01	0.2375
154807	VKORC1L1	S027	Human	Liver	HCC	1.51e-26	2.82e+00	0.2446
154807	VKORC1L1	S028	Human	Liver	HCC	2.07e-48	3.08e+00	0.2503
154807	VKORC1L1	S029	Human	Liver	HCC	5.66e-45	2.99e+00	0.2581
154807	VKORC1L1	TD9	Human	Lung	IAC	1.79e-03	2.89e-01	0.088
154807	VKORC1L1	RNA-P17T-P17T-2	Human	Lung	IAC	3.58e-04	4.02e-01	0.3371
154807	VKORC1L1	RNA-P17T-P17T-4	Human	Lung	IAC	1.54e-04	5.95e-01	0.343
154807	VKORC1L1	RNA-P17T-P17T-6	Human	Lung	IAC	7.74e-03	2.06e-01	0.3385
154807	VKORC1L1	RNA-P25T1-P25T1-1	Human	Lung	AIS	3.88e-05	3.62e-01	-0.2116
154807	VKORC1L1	RNA-P25T1-P25T1-4	Human	Lung	AIS	4.84e-02	2.76e-01	-0.2119
154807	VKORC1L1	RNA-P6T2-P6T2-1	Human	Lung	IAC	5.41e-13	4.68e-01	-0.0166
154807	VKORC1L1	RNA-P6T2-P6T2-2	Human	Lung	IAC	2.66e-13	3.72e-01	-0.0132
154807	VKORC1L1	RNA-P6T2-P6T2-3	Human	Lung	IAC	2.20e-20	5.05e-01	-0.013

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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
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
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:000697910	Cervix	CC	response to oxidative stress	102/2311	446/18723	2.99e-10	4.36e-08	102
GO:006219710	Cervix	CC	cellular response to chemical stress	76/2311	337/18723	1.01e-07	5.25e-06	76
GO:003459910	Cervix	CC	cellular response to oxidative stress	63/2311	288/18723	3.58e-06	9.50e-05	63
GO:0006979111	Esophagus	ESCC	response to oxidative stress	303/8552	446/18723	7.15e-22	1.30e-19	303
GO:0062197111	Esophagus	ESCC	cellular response to chemical stress	234/8552	337/18723	5.37e-19	5.97e-17	234
GO:0034599111	Esophagus	ESCC	cellular response to oxidative stress	197/8552	288/18723	3.76e-15	2.15e-13	197
GO:190166112	Esophagus	ESCC	quinone metabolic process	34/8552	40/18723	3.00e-07	4.27e-06	34
GO:00067661	Esophagus	ESCC	vitamin metabolic process	67/8552	106/18723	2.03e-04	1.28e-03	67
GO:00421805	Esophagus	ESCC	cellular ketone metabolic process	120/8552	211/18723	6.70e-04	3.55e-03	120
GO:00069797	Liver	NAFLD	response to oxidative stress	78/1882	446/18723	7.85e-07	4.29e-05	78
GO:00621977	Liver	NAFLD	cellular response to chemical stress	54/1882	337/18723	3.83e-04	5.73e-03	54
GO:00345997	Liver	NAFLD	cellular response to oxidative stress	46/1882	288/18723	1.07e-03	1.25e-02	46
GO:00421803	Liver	NAFLD	cellular ketone metabolic process	35/1882	211/18723	2.09e-03	2.06e-02	35
GO:000697912	Liver	Cirrhotic	response to oxidative stress	196/4634	446/18723	2.80e-19	5.86e-17	196
GO:006219712	Liver	Cirrhotic	cellular response to chemical stress	147/4634	337/18723	1.84e-14	1.72e-12	147
GO:003459912	Liver	Cirrhotic	cellular response to oxidative stress	127/4634	288/18723	4.29e-13	3.32e-11	127
GO:004218011	Liver	Cirrhotic	cellular ketone metabolic process	80/4634	211/18723	1.40e-05	1.95e-04	80
GO:19016612	Liver	Cirrhotic	quinone metabolic process	18/4634	40/18723	4.11e-03	2.20e-02	18
GO:000697922	Liver	HCC	response to oxidative stress	281/7958	446/18723	9.75e-19	1.24e-16	281
GO:006219722	Liver	HCC	cellular response to chemical stress	216/7958	337/18723	6.86e-16	5.44e-14	216

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa012405	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0124012	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa01240	Liver	Cirrhotic	Biosynthesis of cofactors	66/2530	153/8465	3.11e-04	1.99e-03	1.23e-03	66
hsa012401	Liver	Cirrhotic	Biosynthesis of cofactors	66/2530	153/8465	3.11e-04	1.99e-03	1.23e-03	66
hsa012402	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa012403	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa012404	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa00130	Oral cavity	OSCC	Ubiquinone and other terpenoid-quinone biosynthesis	9/3704	11/8465	1.19e-02	2.62e-02	1.33e-02	9
hsa0124011	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa001301	Oral cavity	OSCC	Ubiquinone and other terpenoid-quinone biosynthesis	9/3704	11/8465	1.19e-02	2.62e-02	1.33e-02	9
hsa001302	Oral cavity	LP	Ubiquinone and other terpenoid-quinone biosynthesis	8/2418	11/8465	3.03e-03	1.29e-02	8.35e-03	8
hsa0124021	Oral cavity	LP	Biosynthesis of cofactors	57/2418	153/8465	1.17e-02	3.91e-02	2.52e-02	57
hsa001303	Oral cavity	LP	Ubiquinone and other terpenoid-quinone biosynthesis	8/2418	11/8465	3.03e-03	1.29e-02	8.35e-03	8
hsa0124031	Oral cavity	LP	Biosynthesis of cofactors	57/2418	153/8465	1.17e-02	3.91e-02	2.52e-02	57

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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

VKORC1L1

SNV

Missense_Mutation

novel

c.127N>A

p.Asp43Asn

p.D43N

Q8N0U8

protein_coding

tolerated(0.07)

probably_damaging(0.918)

TCGA-C5-A2LV-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

VKORC1L1

SNV

Missense_Mutation

c.319N>T

p.Arg107Cys

p.R107C

Q8N0U8

protein_coding

deleterious_low_confidence(0.01)

benign(0)

TCGA-JW-A5VI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

topotecan

VKORC1L1

SNV

Missense_Mutation

c.395N>T

p.Ala132Val

p.A132V

Q8N0U8

protein_coding

deleterious_low_confidence(0)

benign(0.06)

TCGA-AZ-4313-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

VKORC1L1

SNV

Missense_Mutation

c.281N>A

p.Ser94Tyr

p.S94Y

Q8N0U8

protein_coding

deleterious_low_confidence(0)

benign(0.022)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

VKORC1L1

SNV

Missense_Mutation

c.365C>T

p.Thr122Met

p.T122M

Q8N0U8

protein_coding

tolerated_low_confidence(0.07)

probably_damaging(0.974)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

VKORC1L1

SNV

Missense_Mutation

novel

c.209N>A

p.Arg70His

p.R70H

Q8N0U8

protein_coding

tolerated_low_confidence(0.14)

probably_damaging(0.916)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

VKORC1L1

SNV

Missense_Mutation

c.304C>A

p.Leu102Met

p.L102M

Q8N0U8

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.96)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

VKORC1L1

SNV

Missense_Mutation

novel

c.355N>A

p.Gln119Lys

p.Q119K

Q8N0U8

protein_coding

tolerated_low_confidence(0.79)

probably_damaging(0.98)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

VKORC1L1

SNV

Missense_Mutation

novel

c.164N>T

p.Trp55Leu

p.W55L

Q8N0U8

protein_coding

tolerated(0.67)

benign(0.355)

TCGA-DD-AAE2-01

Liver

liver hepatocellular carcinoma

Male

<65

I/II

Unknown

VKORC1L1

SNV

Missense_Mutation

novel

c.10N>T

p.Pro4Ser

p.P4S

Q8N0U8

protein_coding

deleterious_low_confidence(0.01)

benign(0.033)

TCGA-56-8305-01

Lung

lung squamous cell carcinoma

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
154807	VKORC1L1	DRUGGABLE GENOME, ENZYME		MENADIONE	MENADIONE
154807	VKORC1L1	DRUGGABLE GENOME, ENZYME		MENADIONE	MENADIONE
154807	VKORC1L1	DRUGGABLE GENOME, ENZYME		warfarin	WARFARIN	29054760
154807	VKORC1L1	DRUGGABLE GENOME, ENZYME		WARFARIN	WARFARIN
154807	VKORC1L1	DRUGGABLE GENOME, ENZYME		WARFARIN	WARFARIN

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