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: WASF2

Gene summary for WASF2

Gene summary.

Gene information	Species	Human
	Gene symbol	WASF2
	Gene ID	10163
	Gene name	WASP family member 2
	Gene Alias	IMD2
	Cytomap	1p36.11
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q9Y6W5

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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
10163	WASF2	HTA11_3410_2000001011	Human	Colorectum	AD	6.23e-09	4.23e-01	0.0155
10163	WASF2	HTA11_2487_2000001011	Human	Colorectum	SER	2.78e-18	9.50e-01	-0.1808
10163	WASF2	HTA11_1938_2000001011	Human	Colorectum	AD	3.10e-24	1.08e+00	-0.0811
10163	WASF2	HTA11_78_2000001011	Human	Colorectum	AD	5.20e-08	7.20e-01	-0.1088
10163	WASF2	HTA11_347_2000001011	Human	Colorectum	AD	8.31e-31	9.92e-01	-0.1954
10163	WASF2	HTA11_411_2000001011	Human	Colorectum	SER	1.33e-14	1.71e+00	-0.2602
10163	WASF2	HTA11_2112_2000001011	Human	Colorectum	SER	4.92e-13	1.17e+00	-0.2196
10163	WASF2	HTA11_3361_2000001011	Human	Colorectum	AD	3.99e-07	6.57e-01	-0.1207
10163	WASF2	HTA11_83_2000001011	Human	Colorectum	SER	7.47e-07	6.84e-01	-0.1526
10163	WASF2	HTA11_696_2000001011	Human	Colorectum	AD	7.02e-26	1.02e+00	-0.1464
10163	WASF2	HTA11_866_2000001011	Human	Colorectum	AD	1.60e-17	7.72e-01	-0.1001
10163	WASF2	HTA11_1391_2000001011	Human	Colorectum	AD	3.87e-17	9.68e-01	-0.059
10163	WASF2	HTA11_5212_2000001011	Human	Colorectum	AD	1.01e-03	6.45e-01	-0.2061
10163	WASF2	HTA11_546_2000001011	Human	Colorectum	AD	1.31e-06	6.87e-01	-0.0842
10163	WASF2	HTA11_866_3004761011	Human	Colorectum	AD	7.94e-08	4.55e-01	0.096
10163	WASF2	HTA11_4255_2000001011	Human	Colorectum	SER	5.09e-08	8.63e-01	0.0446
10163	WASF2	HTA11_9408_2000001011	Human	Colorectum	AD	1.84e-12	1.29e+00	0.0451
10163	WASF2	HTA11_8622_2000001021	Human	Colorectum	SER	1.70e-03	6.20e-01	0.0528
10163	WASF2	HTA11_7663_2000001011	Human	Colorectum	SER	9.41e-06	8.44e-01	0.0131
10163	WASF2	HTA11_10623_2000001011	Human	Colorectum	AD	6.93e-13	9.84e-01	-0.0177

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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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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
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:003083316	Prostate	BPH	regulation of actin filament polymerization	57/3107	172/18723	7.52e-08	1.92e-06	57
GO:003083210	Prostate	BPH	regulation of actin filament length	61/3107	189/18723	7.89e-08	2.00e-06	61
GO:00343149	Prostate	BPH	Arp2/3 complex-mediated actin nucleation	21/3107	39/18723	1.13e-07	2.72e-06	21
GO:005149218	Prostate	BPH	regulation of stress fiber assembly	36/3107	91/18723	1.43e-07	3.36e-06	36
GO:190290410	Prostate	BPH	negative regulation of supramolecular fiber organization	55/3107	167/18723	1.60e-07	3.63e-06	55
GO:19027439	Prostate	BPH	regulation of lamellipodium organization	23/3107	54/18723	5.78e-06	8.47e-05	23
GO:00975819	Prostate	BPH	lamellipodium organization	32/3107	90/18723	1.01e-05	1.41e-04	32
GO:00450106	Prostate	BPH	actin nucleation	22/3107	52/18723	1.05e-05	1.44e-04	22
GO:005149410	Prostate	BPH	negative regulation of cytoskeleton organization	49/3107	163/18723	1.32e-05	1.74e-04	49
GO:19027459	Prostate	BPH	positive regulation of lamellipodium organization	17/3107	37/18723	2.89e-05	3.34e-04	17
GO:00508087	Prostate	BPH	synapse organization	103/3107	426/18723	3.19e-05	3.61e-04	103
GO:00991736	Prostate	BPH	postsynapse organization	49/3107	168/18723	3.20e-05	3.61e-04	49
GO:001063916	Prostate	BPH	negative regulation of organelle organization	87/3107	348/18723	3.56e-05	3.90e-04	87
GO:00105928	Prostate	BPH	positive regulation of lamellipodium assembly	14/3107	29/18723	7.48e-05	7.24e-04	14
GO:00300489	Prostate	BPH	actin filament-based movement	38/3107	127/18723	1.31e-04	1.18e-03	38
GO:00604919	Prostate	BPH	regulation of cell projection assembly	51/3107	188/18723	1.73e-04	1.48e-03	51
GO:00105918	Prostate	BPH	regulation of lamellipodium assembly	17/3107	42/18723	2.01e-04	1.64e-03	17
GO:012003210	Prostate	BPH	regulation of plasma membrane bounded cell projection assembly	50/3107	186/18723	2.53e-04	2.00e-03	50
GO:20006012	Prostate	BPH	positive regulation of Arp2/3 complex-mediated actin nucleation	7/3107	10/18723	2.59e-04	2.04e-03	7
GO:00514976	Prostate	BPH	negative regulation of stress fiber assembly	14/3107	32/18723	2.77e-04	2.16e-03	14

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa05100	Colorectum	AD	Bacterial invasion of epithelial cells	44/2092	77/8465	1.13e-09	2.22e-08	1.42e-08	44
hsa04520	Colorectum	AD	Adherens junction	50/2092	93/8465	1.52e-09	2.83e-08	1.81e-08	50
hsa04666	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa05135	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa051311	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa051001	Colorectum	AD	Bacterial invasion of epithelial cells	44/2092	77/8465	1.13e-09	2.22e-08	1.42e-08	44
hsa045201	Colorectum	AD	Adherens junction	50/2092	93/8465	1.52e-09	2.83e-08	1.81e-08	50
hsa046661	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa051301	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa051351	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa051312	Colorectum	SER	Shigellosis	87/1580	247/8465	3.07e-10	7.27e-09	5.28e-09	87
hsa051002	Colorectum	SER	Bacterial invasion of epithelial cells	36/1580	77/8465	1.56e-08	3.45e-07	2.50e-07	36
hsa046662	Colorectum	SER	Fc gamma R-mediated phagocytosis	39/1580	97/8465	5.84e-07	9.70e-06	7.04e-06	39
hsa045202	Colorectum	SER	Adherens junction	37/1580	93/8465	1.54e-06	2.35e-05	1.71e-05	37
hsa051302	Colorectum	SER	Pathogenic Escherichia coli infection	60/1580	197/8465	3.63e-05	4.31e-04	3.13e-04	60
hsa051352	Colorectum	SER	Yersinia infection	43/1580	137/8465	2.15e-04	2.10e-03	1.52e-03	43

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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

WASF2

SNV

Missense_Mutation

novel

c.324G>T

p.Gln108His

p.Q108H

Q9Y6W5

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WASF2

SNV

Missense_Mutation

c.208G>C

p.Glu70Gln

p.E70Q

Q9Y6W5

protein_coding

deleterious(0.01)

benign(0.077)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WASF2

SNV

Missense_Mutation

c.786N>G

p.Phe262Leu

p.F262L

Q9Y6W5

protein_coding

tolerated(0.25)

benign(0.173)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WASF2

insertion

In_Frame_Ins

novel

c.703_704insGACTGAGGTGGGAGGATCGCTTGAGCCTGGGAGGTT

p.Ile235delinsArgLeuArgTrpGluAspArgLeuSerLeuGlyGlyPhe

p.I235delinsRLRWEDRLSLGGF

Q9Y6W5

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WASF2

SNV

Missense_Mutation

novel

c.1423C>T

p.Arg475Cys

p.R475C

Q9Y6W5

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WASF2

SNV

Missense_Mutation

c.1438G>A

p.Glu480Lys

p.E480K

Q9Y6W5

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-MY-A5BD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WASF2

SNV

Missense_Mutation

c.468N>G

p.Phe156Leu

p.F156L

Q9Y6W5

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-UC-A7PF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

WASF2

SNV

Missense_Mutation

c.584A>C

p.Lys195Thr

p.K195T

Q9Y6W5

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AA-3855-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

WASF2

SNV

Missense_Mutation

novel

c.263A>G

p.Glu88Gly

p.E88G

Q9Y6W5

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

WASF2

SNV

Missense_Mutation

novel

c.612N>T

p.Glu204Asp

p.E204D

Q9Y6W5

protein_coding

deleterious(0.05)

probably_damaging(0.978)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

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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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