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: RNF13

Gene summary for RNF13

Gene summary.

Gene information	Species	Human
	Gene symbol	RNF13
	Gene ID	11342
	Gene name	ring finger protein 13
	Gene Alias	DEE73
	Cytomap	3q25.1
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	O43567

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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
11342	RNF13	CA_HPV_1	Human	Cervix	CC	2.99e-02	2.92e-02	0.0264
11342	RNF13	CA_HPV_3	Human	Cervix	CC	9.59e-04	1.81e-01	0.0414
11342	RNF13	CCI_2	Human	Cervix	CC	2.72e-15	1.82e+00	0.5249
11342	RNF13	CCI_3	Human	Cervix	CC	4.36e-13	1.14e+00	0.516
11342	RNF13	L1	Human	Cervix	CC	1.87e-02	6.87e-02	0.0802
11342	RNF13	HTA11_3410_2000001011	Human	Colorectum	AD	4.89e-22	-5.79e-01	0.0155
11342	RNF13	HTA11_2487_2000001011	Human	Colorectum	SER	1.22e-08	-5.30e-01	-0.1808
11342	RNF13	HTA11_1938_2000001011	Human	Colorectum	AD	1.50e-06	-5.38e-01	-0.0811
11342	RNF13	HTA11_78_2000001011	Human	Colorectum	AD	6.36e-03	-3.77e-01	-0.1088
11342	RNF13	HTA11_347_2000001011	Human	Colorectum	AD	8.09e-09	-4.30e-01	-0.1954
11342	RNF13	HTA11_3361_2000001011	Human	Colorectum	AD	1.08e-09	-5.77e-01	-0.1207
11342	RNF13	HTA11_83_2000001011	Human	Colorectum	SER	2.65e-07	-5.74e-01	-0.1526
11342	RNF13	HTA11_696_2000001011	Human	Colorectum	AD	1.04e-23	-5.38e-01	-0.1464
11342	RNF13	HTA11_866_2000001011	Human	Colorectum	AD	1.41e-22	-5.36e-01	-0.1001
11342	RNF13	HTA11_1391_2000001011	Human	Colorectum	AD	2.46e-11	-5.20e-01	-0.059
11342	RNF13	HTA11_2992_2000001011	Human	Colorectum	SER	4.12e-02	-5.61e-01	-0.1706
11342	RNF13	HTA11_546_2000001011	Human	Colorectum	AD	5.37e-06	-5.72e-01	-0.0842
11342	RNF13	HTA11_7862_2000001011	Human	Colorectum	AD	1.04e-02	-5.27e-01	-0.0179
11342	RNF13	HTA11_866_3004761011	Human	Colorectum	AD	2.84e-14	-5.39e-01	0.096
11342	RNF13	HTA11_8622_2000001021	Human	Colorectum	SER	2.29e-02	-5.42e-01	0.0528

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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
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
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:00310988	Cervix	CC	stress-activated protein kinase signaling cascade	58/2311	247/18723	8.02e-07	2.89e-05	58
GO:00703027	Cervix	CC	regulation of stress-activated protein kinase signaling cascade	46/2311	195/18723	9.35e-06	2.11e-04	46
GO:00703043	Cervix	CC	positive regulation of stress-activated protein kinase signaling cascade	27/2311	128/18723	3.49e-03	2.26e-02	27
GO:00518656	Cervix	CC	protein autoubiquitination	17/2311	73/18723	6.71e-03	3.70e-02	17
GO:0031098	Colorectum	AD	stress-activated protein kinase signaling cascade	74/3918	247/18723	4.80e-04	5.27e-03	74
GO:0051865	Colorectum	AD	protein autoubiquitination	28/3918	73/18723	4.87e-04	5.30e-03	28
GO:0070302	Colorectum	AD	regulation of stress-activated protein kinase signaling cascade	58/3918	195/18723	2.21e-03	1.74e-02	58
GO:00310981	Colorectum	SER	stress-activated protein kinase signaling cascade	54/2897	247/18723	4.65e-03	3.67e-02	54
GO:00310982	Colorectum	MSS	stress-activated protein kinase signaling cascade	67/3467	247/18723	5.28e-04	5.99e-03	67
GO:00518651	Colorectum	MSS	protein autoubiquitination	25/3467	73/18723	1.00e-03	1.00e-02	25
GO:00703021	Colorectum	MSS	regulation of stress-activated protein kinase signaling cascade	52/3467	195/18723	3.07e-03	2.34e-02	52
GO:00310983	Colorectum	FAP	stress-activated protein kinase signaling cascade	61/2622	247/18723	4.79e-06	1.57e-04	61
GO:00703022	Colorectum	FAP	regulation of stress-activated protein kinase signaling cascade	48/2622	195/18723	5.14e-05	1.04e-03	48
GO:00518652	Colorectum	FAP	protein autoubiquitination	22/2622	73/18723	2.88e-04	3.77e-03	22
GO:0070304	Colorectum	FAP	positive regulation of stress-activated protein kinase signaling cascade	31/2622	128/18723	1.35e-03	1.24e-02	31
GO:00310984	Colorectum	CRC	stress-activated protein kinase signaling cascade	51/2078	247/18723	8.35e-06	3.00e-04	51
GO:00703023	Colorectum	CRC	regulation of stress-activated protein kinase signaling cascade	41/2078	195/18723	3.99e-05	9.63e-04	41
GO:00518653	Colorectum	CRC	protein autoubiquitination	18/2078	73/18723	8.33e-04	1.04e-02	18
GO:00703041	Colorectum	CRC	positive regulation of stress-activated protein kinase signaling cascade	25/2078	128/18723	3.44e-03	2.92e-02	25
GO:000020916	Esophagus	HGIN	protein polyubiquitination	58/2587	236/18723	6.29e-06	1.97e-04	58

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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

RNF13

SNV

Missense_Mutation

c.32N>T

p.Ser11Leu

p.S11L

O43567

protein_coding

deleterious_low_confidence(0.03)

benign(0.007)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF13

SNV

Missense_Mutation

novel

c.11C>T

p.Ser4Phe

p.S4F

O43567

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.986)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

RNF13

SNV

Missense_Mutation

novel

c.755N>G

p.Lys252Arg

p.K252R

O43567

protein_coding

tolerated(0.13)

benign(0.057)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

RNF13

deletion

Frame_Shift_Del

c.494delN

p.Gly168AlafsTer5

p.G168Afs*5

O43567

protein_coding

TCGA-G4-6304-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

RNF13

SNV

Missense_Mutation

novel

c.226N>A

p.Ala76Thr

p.A76T

O43567

protein_coding

deleterious(0.03)

possibly_damaging(0.641)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RNF13

SNV

Missense_Mutation

novel

c.661G>T

p.Asp221Tyr

p.D221Y

O43567

protein_coding

deleterious(0)

possibly_damaging(0.468)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

RNF13

SNV

Missense_Mutation

rs751133228

c.670N>G

p.Lys224Glu

p.K224E

O43567

protein_coding

deleterious(0.03)

benign(0.212)

TCGA-AP-A3K1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

RNF13

SNV

Missense_Mutation

novel

c.617N>A

p.Phe206Tyr

p.F206Y

O43567

protein_coding

tolerated(0.62)

benign(0.031)

TCGA-BG-A222-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RNF13

SNV

Missense_Mutation

novel

c.1103N>G

p.Gln368Arg

p.Q368R

O43567

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.932)

TCGA-BG-A222-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RNF13

SNV

Missense_Mutation

c.977N>C

p.Leu326Ser

p.L326S

O43567

protein_coding

deleterious(0)

benign(0.05)

TCGA-BS-A0UJ-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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