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: WWP1

Gene summary for WWP1

Gene summary.

Gene information	Species	Human
	Gene symbol	WWP1
	Gene ID	11059
	Gene name	WW domain containing E3 ubiquitin protein ligase 1
	Gene Alias	AIP5
	Cytomap	8q21.3
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	Q9H0M0

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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
11059	WWP1	GSM4909290	Human	Breast	IDC	3.28e-07	3.90e-01	0.2096
11059	WWP1	GSM4909293	Human	Breast	IDC	8.15e-05	2.41e-01	0.1581
11059	WWP1	GSM4909297	Human	Breast	IDC	1.00e-02	3.07e-01	0.1517
11059	WWP1	GSM4909298	Human	Breast	IDC	2.71e-12	3.68e-01	0.1551
11059	WWP1	GSM4909304	Human	Breast	IDC	2.88e-28	6.35e-01	0.1636
11059	WWP1	GSM4909306	Human	Breast	IDC	1.46e-17	4.85e-01	0.1564
11059	WWP1	GSM4909308	Human	Breast	IDC	1.48e-03	2.17e-01	0.158
11059	WWP1	GSM4909311	Human	Breast	IDC	1.20e-05	1.71e-02	0.1534
11059	WWP1	GSM4909317	Human	Breast	IDC	3.73e-07	3.59e-01	0.1355
11059	WWP1	GSM4909319	Human	Breast	IDC	1.01e-06	-1.41e-02	0.1563
11059	WWP1	M1	Human	Breast	IDC	3.13e-10	4.91e-01	0.1577
11059	WWP1	NCCBC2	Human	Breast	DCIS	7.94e-05	6.14e-01	0.1554
11059	WWP1	DCIS2	Human	Breast	DCIS	1.06e-37	1.77e-01	0.0085
11059	WWP1	CCI_2	Human	Cervix	CC	6.20e-09	1.17e+00	0.5249
11059	WWP1	CCI_3	Human	Cervix	CC	4.72e-08	7.21e-01	0.516
11059	WWP1	HTA11_3410_2000001011	Human	Colorectum	AD	1.43e-20	-4.41e-01	0.0155
11059	WWP1	HTA11_2487_2000001011	Human	Colorectum	SER	1.76e-07	-4.80e-01	-0.1808
11059	WWP1	HTA11_3361_2000001011	Human	Colorectum	AD	1.17e-07	-6.02e-01	-0.1207
11059	WWP1	HTA11_83_2000001011	Human	Colorectum	SER	2.05e-04	-3.67e-01	-0.1526
11059	WWP1	HTA11_696_2000001011	Human	Colorectum	AD	1.66e-07	-4.31e-01	-0.1464

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:004217620	Oral cavity	OSCC	regulation of protein catabolic process	254/7305	391/18723	1.07e-25	3.22e-23	254
GO:001905820	Oral cavity	OSCC	viral life cycle	208/7305	317/18723	4.59e-22	1.00e-19	208
GO:004573220	Oral cavity	OSCC	positive regulation of protein catabolic process	150/7305	231/18723	1.06e-15	7.64e-14	150
GO:000020910	Oral cavity	OSCC	protein polyubiquitination	150/7305	236/18723	1.59e-14	9.27e-13	150
GO:004440320	Oral cavity	OSCC	biological process involved in symbiotic interaction	173/7305	290/18723	6.80e-13	3.19e-11	173
GO:005170120	Oral cavity	OSCC	biological process involved in interaction with host	125/7305	203/18723	5.60e-11	1.74e-09	125
GO:005212620	Oral cavity	OSCC	movement in host environment	106/7305	175/18723	5.84e-09	1.26e-07	106
GO:004440920	Oral cavity	OSCC	entry into host	86/7305	151/18723	5.74e-06	6.37e-05	86
GO:004671820	Oral cavity	OSCC	viral entry into host cell	81/7305	144/18723	1.98e-05	1.89e-04	81
GO:001603233	Oral cavity	NEOLP	viral process	101/2005	415/18723	1.08e-15	5.85e-13	101
GO:000989633	Oral cavity	NEOLP	positive regulation of catabolic process	111/2005	492/18723	1.19e-14	4.72e-12	111
GO:004217634	Oral cavity	NEOLP	regulation of protein catabolic process	92/2005	391/18723	1.77e-13	5.27e-11	92
GO:001905834	Oral cavity	NEOLP	viral life cycle	77/2005	317/18723	3.13e-12	5.82e-10	77
GO:001049831	Oral cavity	NEOLP	proteasomal protein catabolic process	103/2005	490/18723	1.08e-11	1.65e-09	103
GO:004316131	Oral cavity	NEOLP	proteasome-mediated ubiquitin-dependent protein catabolic process	89/2005	412/18723	6.27e-11	7.44e-09	89
GO:004573233	Oral cavity	NEOLP	positive regulation of protein catabolic process	58/2005	231/18723	3.80e-10	3.18e-08	58
GO:004440333	Oral cavity	NEOLP	biological process involved in symbiotic interaction	64/2005	290/18723	1.28e-08	6.01e-07	64
GO:000020931	Oral cavity	NEOLP	protein polyubiquitination	53/2005	236/18723	1.22e-07	4.38e-06	53
GO:005170133	Oral cavity	NEOLP	biological process involved in interaction with host	47/2005	203/18723	2.42e-07	7.85e-06	47
GO:004671832	Oral cavity	NEOLP	viral entry into host cell	36/2005	144/18723	8.75e-07	2.37e-05	36

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414416	Breast	DCIS	Endocytosis	37/846	251/8465	9.92e-03	4.40e-02	3.24e-02	37
hsa0414417	Breast	DCIS	Endocytosis	37/846	251/8465	9.92e-03	4.40e-02	3.24e-02	37
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0414418	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0414419	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa04144	Colorectum	AD	Endocytosis	111/2092	251/8465	5.95e-12	1.42e-10	9.08e-11	111
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041441	Colorectum	AD	Endocytosis	111/2092	251/8465	5.95e-12	1.42e-10	9.08e-11	111
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041442	Colorectum	SER	Endocytosis	81/1580	251/8465	1.14e-07	2.36e-06	1.71e-06	81
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041443	Colorectum	SER	Endocytosis	81/1580	251/8465	1.14e-07	2.36e-06	1.71e-06	81
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041444	Colorectum	MSS	Endocytosis	102/1875	251/8465	1.85e-11	4.43e-10	2.71e-10	102
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041445	Colorectum	MSS	Endocytosis	102/1875	251/8465	1.85e-11	4.43e-10	2.71e-10	102
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041446	Colorectum	FAP	Endocytosis	78/1404	251/8465	6.20e-09	2.96e-07	1.80e-07	78
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51

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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

WWP1

SNV

Missense_Mutation

c.2008C>T

p.His670Tyr

p.H670Y

Q9H0M0

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-A8-A093-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

WWP1

SNV

Missense_Mutation

c.1549N>T

p.His517Tyr

p.H517Y

Q9H0M0

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WWP1

SNV

Missense_Mutation

c.67N>T

p.Thr23Ser

p.T23S

Q9H0M0

protein_coding

tolerated(0.1)

benign(0.05)

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WWP1

SNV

Missense_Mutation

c.1073N>T

p.Arg358Ile

p.R358I

Q9H0M0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WWP1

SNV

Missense_Mutation

rs746179892

c.1783N>T

p.Arg595Cys

p.R595C

Q9H0M0

protein_coding

deleterious(0.01)

benign(0.116)

TCGA-EW-A1PH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

WWP1

SNV

Missense_Mutation

c.1960C>G

p.Leu654Val

p.L654V

Q9H0M0

protein_coding

deleterious(0)

probably_damaging(0.922)

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

WWP1

SNV

Missense_Mutation

novel

c.631N>C

p.Asp211His

p.D211H

Q9H0M0

protein_coding

tolerated(0.16)

possibly_damaging(0.491)

TCGA-LL-A6FP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

WWP1

insertion

In_Frame_Ins

novel

c.1945_1946insATTTCCAGTGTATTTGTA

p.Thr648_Ile649insAsnPheGlnCysIleCys

p.T648_I649insNFQCIC

Q9H0M0

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WWP1

insertion

In_Frame_Ins

novel

c.1024_1025insAACTATTACATA

p.Gln342_Ser343insLeuLeuHisLys

p.Q342_S343insLLHK

Q9H0M0

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

WWP1

insertion

Frame_Shift_Ins

novel

c.1026_1027insATTTTAATTTTTTGCCCCGTGTT

p.Ser343IlefsTer114

p.S343Ifs*114

Q9H0M0

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive 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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