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: RABGAP1L

Gene summary for RABGAP1L

Gene summary.

Gene information	Species	Human
	Gene symbol	RABGAP1L
	Gene ID	9910
	Gene name	RAB GTPase activating protein 1 like
	Gene Alias	HHL
	Cytomap	1q25.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q5R372

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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
9910	RABGAP1L	CCI_1	Human	Cervix	CC	7.46e-30	3.06e+00	0.528
9910	RABGAP1L	CCI_2	Human	Cervix	CC	5.17e-13	1.41e+00	0.5249
9910	RABGAP1L	CCI_3	Human	Cervix	CC	2.39e-36	1.94e+00	0.516
9910	RABGAP1L	HTA11_3410_2000001011	Human	Colorectum	AD	7.03e-20	-5.31e-01	0.0155
9910	RABGAP1L	HTA11_1938_2000001011	Human	Colorectum	AD	3.15e-04	4.80e-01	-0.0811
9910	RABGAP1L	HTA11_347_2000001011	Human	Colorectum	AD	5.48e-21	8.54e-01	-0.1954
9910	RABGAP1L	HTA11_411_2000001011	Human	Colorectum	SER	3.86e-07	9.07e-01	-0.2602
9910	RABGAP1L	HTA11_1391_2000001011	Human	Colorectum	AD	1.25e-02	4.74e-01	-0.059
9910	RABGAP1L	HTA11_866_3004761011	Human	Colorectum	AD	2.01e-05	-4.40e-01	0.096
9910	RABGAP1L	HTA11_8622_2000001021	Human	Colorectum	SER	3.00e-06	-4.02e-01	0.0528
9910	RABGAP1L	HTA11_10711_2000001011	Human	Colorectum	AD	1.65e-03	-4.61e-01	0.0338
9910	RABGAP1L	HTA11_7696_3000711011	Human	Colorectum	AD	3.98e-03	-3.43e-01	0.0674
9910	RABGAP1L	HTA11_99999965062_69753	Human	Colorectum	MSI-H	5.68e-16	1.06e+00	0.3487
9910	RABGAP1L	HTA11_99999973899_84307	Human	Colorectum	MSS	4.34e-02	-4.97e-01	0.2585
9910	RABGAP1L	HTA11_99999974143_84620	Human	Colorectum	MSS	2.99e-15	-4.14e-01	0.3005
9910	RABGAP1L	F007	Human	Colorectum	FAP	1.42e-04	-2.90e-01	0.1176
9910	RABGAP1L	A001-C-207	Human	Colorectum	FAP	7.34e-04	-3.14e-01	0.1278
9910	RABGAP1L	A015-C-203	Human	Colorectum	FAP	1.50e-31	-5.22e-01	-0.1294
9910	RABGAP1L	A015-C-204	Human	Colorectum	FAP	5.45e-08	-3.53e-01	-0.0228
9910	RABGAP1L	A014-C-040	Human	Colorectum	FAP	4.02e-05	-3.22e-01	-0.1184

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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

∗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:00430877	Cervix	CC	regulation of GTPase activity	79/2311	348/18723	4.21e-08	2.60e-06	79
GO:00435476	Cervix	CC	positive regulation of GTPase activity	53/2311	255/18723	8.72e-05	1.16e-03	53
GO:0043087	Colorectum	AD	regulation of GTPase activity	110/3918	348/18723	1.64e-06	5.03e-05	110
GO:0043547	Colorectum	AD	positive regulation of GTPase activity	75/3918	255/18723	7.95e-04	7.91e-03	75
GO:00430871	Colorectum	SER	regulation of GTPase activity	77/2897	348/18723	5.90e-04	8.07e-03	77
GO:00430872	Colorectum	MSS	regulation of GTPase activity	101/3467	348/18723	1.00e-06	3.46e-05	101
GO:00435471	Colorectum	MSS	positive regulation of GTPase activity	68/3467	255/18723	7.97e-04	8.38e-03	68
GO:00430873	Colorectum	FAP	regulation of GTPase activity	85/2622	348/18723	1.20e-07	7.68e-06	85
GO:00435472	Colorectum	FAP	positive regulation of GTPase activity	61/2622	255/18723	1.39e-05	3.73e-04	61
GO:0090630	Colorectum	FAP	activation of GTPase activity	27/2622	115/18723	4.23e-03	2.90e-02	27
GO:00430874	Colorectum	CRC	regulation of GTPase activity	69/2078	348/18723	1.11e-06	6.69e-05	69
GO:00435473	Colorectum	CRC	positive regulation of GTPase activity	49/2078	255/18723	8.67e-05	1.77e-03	49
GO:00430878	Endometrium	AEH	regulation of GTPase activity	66/2100	348/18723	1.26e-05	2.77e-04	66
GO:00435477	Endometrium	AEH	positive regulation of GTPase activity	48/2100	255/18723	2.18e-04	2.67e-03	48
GO:00906304	Endometrium	AEH	activation of GTPase activity	22/2100	115/18723	8.42e-03	4.60e-02	22
GO:004308712	Endometrium	EEC	regulation of GTPase activity	67/2168	348/18723	1.84e-05	3.43e-04	67
GO:004354712	Endometrium	EEC	positive regulation of GTPase activity	50/2168	255/18723	1.26e-04	1.66e-03	50
GO:009063012	Endometrium	EEC	activation of GTPase activity	23/2168	115/18723	6.04e-03	3.57e-02	23
GO:004308715	Esophagus	ESCC	regulation of GTPase activity	183/8552	348/18723	5.34e-03	2.00e-02	183
GO:00430875	Liver	NAFLD	regulation of GTPase activity	62/1882	348/18723	5.65e-06	2.03e-04	62

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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

RABGAP1L

SNV

Missense_Mutation

c.536N>A

p.Ser179Tyr

p.S179Y

Q5R372

protein_coding

tolerated(0.47)

possibly_damaging(0.703)

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

RABGAP1L

SNV

Missense_Mutation

novel

c.56C>A

p.Thr19Lys

p.T19K

Q5R372

protein_coding

deleterious(0)

benign(0.196)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

RABGAP1L

SNV

Missense_Mutation

c.1144G>C

p.Glu382Gln

p.E382Q

Q5R372

protein_coding

deleterious(0.01)

probably_damaging(0.982)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RABGAP1L

SNV

Missense_Mutation

novel

c.871T>A

p.Phe291Ile

p.F291I

Q5R372

protein_coding

deleterious(0)

probably_damaging(0.924)

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RABGAP1L

SNV

Missense_Mutation

novel

c.1154A>G

p.Lys385Arg

p.K385R

Q5R372

protein_coding

tolerated(0.22)

probably_damaging(1)

TCGA-AR-A5QN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

taxotere

RABGAP1L

SNV

Missense_Mutation

novel

c.56N>A

p.Thr19Lys

p.T19K

Q5R372

protein_coding

deleterious(0)

benign(0.196)

TCGA-B6-A1KF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RABGAP1L

SNV

Missense_Mutation

c.872N>C

p.Phe291Ser

p.F291S

Q5R372

protein_coding

deleterious(0)

probably_damaging(0.944)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

RABGAP1L

insertion

Nonsense_Mutation

novel

c.1152_1153insTCATAGCTCTTTCCCATGGATTCCTAT

p.Pro384_Lys385insSerTerLeuPheProMetAspSerTyr

p.P384_K385insS*LFPMDSY

Q5R372

protein_coding

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RABGAP1L

insertion

In_Frame_Ins

novel

c.869_870insTAC

p.Asn290_Phe291insThr

p.N290_F291insT

Q5R372

protein_coding

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RABGAP1L

insertion

Frame_Shift_Ins

novel

c.634_635insCAGACTGGGACAGACTGCCTCCTCAAGTGGGTCCCCC

p.Ser212ThrfsTer36

p.S212Tfs*36

Q5R372

protein_coding

TCGA-AO-A124-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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
9910	RABGAP1L	NA		ethanol	ALCOHOL

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