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: RALGPS2

Gene summary for RALGPS2

Gene summary.

Gene information	Species	Human
	Gene symbol	RALGPS2
	Gene ID	55103
	Gene name	Ral GEF with PH domain and SH3 binding motif 2
	Gene Alias	dJ595C2.1
	Cytomap	1q25.2
	Gene Type	protein-coding
	GO ID	GO:0007154
	UniProtAcc	Q86X27

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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
55103	RALGPS2	HTA11_3410_2000001011	Human	Colorectum	AD	1.63e-16	-6.12e-01	0.0155
55103	RALGPS2	HTA11_3361_2000001011	Human	Colorectum	AD	1.83e-02	-4.51e-01	-0.1207
55103	RALGPS2	HTA11_866_2000001011	Human	Colorectum	AD	3.96e-02	-3.25e-01	-0.1001
55103	RALGPS2	HTA11_546_2000001011	Human	Colorectum	AD	2.17e-02	-4.40e-01	-0.0842
55103	RALGPS2	HTA11_866_3004761011	Human	Colorectum	AD	3.47e-09	-5.18e-01	0.096
55103	RALGPS2	HTA11_10711_2000001011	Human	Colorectum	AD	1.84e-02	-4.55e-01	0.0338
55103	RALGPS2	HTA11_7696_3000711011	Human	Colorectum	AD	3.60e-11	-4.66e-01	0.0674
55103	RALGPS2	HTA11_99999970781_79442	Human	Colorectum	MSS	3.36e-12	-5.30e-01	0.294
55103	RALGPS2	HTA11_99999971662_82457	Human	Colorectum	MSS	1.20e-02	-2.79e-01	0.3859
55103	RALGPS2	HTA11_99999973899_84307	Human	Colorectum	MSS	3.75e-06	-6.60e-01	0.2585
55103	RALGPS2	HTA11_99999974143_84620	Human	Colorectum	MSS	5.80e-19	-5.87e-01	0.3005
55103	RALGPS2	A002-C-010	Human	Colorectum	FAP	3.37e-02	-1.56e-01	0.242
55103	RALGPS2	A015-C-203	Human	Colorectum	FAP	1.84e-25	-2.83e-01	-0.1294
55103	RALGPS2	A015-C-204	Human	Colorectum	FAP	9.99e-03	-4.27e-02	-0.0228
55103	RALGPS2	A014-C-040	Human	Colorectum	FAP	3.88e-03	-2.36e-01	-0.1184
55103	RALGPS2	A002-C-201	Human	Colorectum	FAP	3.18e-11	-2.86e-01	0.0324
55103	RALGPS2	A002-C-203	Human	Colorectum	FAP	4.66e-02	-1.75e-01	0.2786
55103	RALGPS2	A001-C-119	Human	Colorectum	FAP	1.95e-04	-2.71e-01	-0.1557
55103	RALGPS2	A001-C-108	Human	Colorectum	FAP	1.70e-13	-7.23e-02	-0.0272
55103	RALGPS2	A002-C-205	Human	Colorectum	FAP	2.57e-19	-2.60e-01	-0.1236

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:0007265	Colorectum	AD	Ras protein signal transduction	104/3918	337/18723	1.01e-05	2.35e-04	104
GO:0051056	Colorectum	AD	regulation of small GTPase mediated signal transduction	94/3918	302/18723	1.81e-05	3.76e-04	94
GO:0046578	Colorectum	AD	regulation of Ras protein signal transduction	56/3918	189/18723	2.85e-03	2.14e-02	56
GO:00072651	Colorectum	MSS	Ras protein signal transduction	91/3467	337/18723	7.20e-05	1.21e-03	91
GO:00510561	Colorectum	MSS	regulation of small GTPase mediated signal transduction	82/3467	302/18723	1.31e-04	1.99e-03	82
GO:00510562	Colorectum	FAP	regulation of small GTPase mediated signal transduction	78/2622	302/18723	3.25e-08	2.85e-06	78
GO:00072652	Colorectum	FAP	Ras protein signal transduction	80/2622	337/18723	9.61e-07	4.33e-05	80
GO:00465781	Colorectum	FAP	regulation of Ras protein signal transduction	47/2622	189/18723	4.67e-05	9.60e-04	47
GO:00510563	Colorectum	CRC	regulation of small GTPase mediated signal transduction	69/2078	302/18723	3.34e-09	9.08e-07	69
GO:00072653	Colorectum	CRC	Ras protein signal transduction	70/2078	337/18723	1.49e-07	1.66e-05	70
GO:00465782	Colorectum	CRC	regulation of Ras protein signal transduction	43/2078	189/18723	3.26e-06	1.47e-04	43
GO:000726510	Esophagus	ESCC	Ras protein signal transduction	201/8552	337/18723	1.44e-07	2.30e-06	201
GO:00465789	Esophagus	ESCC	regulation of Ras protein signal transduction	106/8552	189/18723	2.49e-03	1.08e-02	106
GO:005105610	Esophagus	ESCC	regulation of small GTPase mediated signal transduction	157/8552	302/18723	1.55e-02	4.98e-02	157
GO:00072654	Liver	NAFLD	Ras protein signal transduction	66/1882	337/18723	8.43e-08	7.09e-06	66
GO:00510564	Liver	NAFLD	regulation of small GTPase mediated signal transduction	56/1882	302/18723	4.62e-06	1.75e-04	56
GO:00465783	Liver	NAFLD	regulation of Ras protein signal transduction	38/1882	189/18723	2.42e-05	6.61e-04	38
GO:000726511	Liver	Cirrhotic	Ras protein signal transduction	119/4634	337/18723	8.16e-06	1.22e-04	119
GO:000726521	Liver	HCC	Ras protein signal transduction	187/7958	337/18723	8.89e-07	1.35e-05	187
GO:004657811	Liver	HCC	regulation of Ras protein signal transduction	100/7958	189/18723	2.42e-03	1.18e-02	100

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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

RALGPS2

SNV

Missense_Mutation

c.585N>C

p.Met195Ile

p.M195I

Q86X27

protein_coding

tolerated(0.05)

possibly_damaging(0.471)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RALGPS2

SNV

Missense_Mutation

rs569583893

c.980C>T

p.Pro327Leu

p.P327L

Q86X27

protein_coding

deleterious(0.05)

benign(0.043)

TCGA-E2-A15M-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

RALGPS2

deletion

Frame_Shift_Del

novel

c.1246delA

p.Arg416GlyfsTer11

p.R416Gfs*11

Q86X27

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

RALGPS2

SNV

Missense_Mutation

novel

c.696N>A

p.Met232Ile

p.M232I

Q86X27

protein_coding

deleterious(0.02)

possibly_damaging(0.719)

TCGA-C5-A8YQ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

RALGPS2

SNV

Missense_Mutation

c.641N>T

p.Ser214Leu

p.S214L

Q86X27

protein_coding

tolerated(0.36)

benign(0.09)

TCGA-DS-A0VN-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RALGPS2

SNV

Missense_Mutation

rs748539541

c.130G>A

p.Asp44Asn

p.D44N

Q86X27

protein_coding

tolerated(0.06)

possibly_damaging(0.694)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RALGPS2

SNV

Missense_Mutation

rs762927733

c.1637C>T

p.Ser546Leu

p.S546L

Q86X27

protein_coding

deleterious(0.03)

benign(0.07)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RALGPS2

SNV

Missense_Mutation

c.244N>C

p.Glu82Gln

p.E82Q

Q86X27

protein_coding

deleterious(0.01)

probably_damaging(0.963)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RALGPS2

SNV

Missense_Mutation

c.1159N>A

p.Glu387Lys

p.E387K

Q86X27

protein_coding

tolerated(0.77)

benign(0.13)

TCGA-IR-A3LI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RALGPS2

SNV

Missense_Mutation

rs762927733

c.1637N>T

p.Ser546Leu

p.S546L

Q86X27

protein_coding

deleterious(0.03)

benign(0.07)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

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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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