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: WASF1

Gene summary for WASF1

Gene summary.

Gene information	Species	Human
	Gene symbol	WASF1
	Gene ID	8936
	Gene name	WASP family member 1
	Gene Alias	NEDALVS
	Cytomap	6q21
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q92558

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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
8936	WASF1	LZE4T	Human	Esophagus	ESCC	6.04e-09	4.05e-01	0.0811
8936	WASF1	P2T-E	Human	Esophagus	ESCC	7.33e-10	1.57e-01	0.1177
8936	WASF1	P4T-E	Human	Esophagus	ESCC	3.85e-16	3.15e-01	0.1323
8936	WASF1	P5T-E	Human	Esophagus	ESCC	6.33e-04	-3.88e-03	0.1327
8936	WASF1	P8T-E	Human	Esophagus	ESCC	3.29e-04	8.46e-02	0.0889
8936	WASF1	P9T-E	Human	Esophagus	ESCC	1.01e-09	2.37e-01	0.1131
8936	WASF1	P10T-E	Human	Esophagus	ESCC	2.35e-45	8.25e-01	0.116
8936	WASF1	P11T-E	Human	Esophagus	ESCC	8.60e-07	2.31e-01	0.1426
8936	WASF1	P12T-E	Human	Esophagus	ESCC	3.88e-18	3.21e-01	0.1122
8936	WASF1	P15T-E	Human	Esophagus	ESCC	6.53e-11	3.57e-01	0.1149
8936	WASF1	P16T-E	Human	Esophagus	ESCC	1.35e-16	2.82e-01	0.1153
8936	WASF1	P20T-E	Human	Esophagus	ESCC	1.44e-04	8.18e-02	0.1124
8936	WASF1	P21T-E	Human	Esophagus	ESCC	8.33e-07	1.01e-01	0.1617
8936	WASF1	P22T-E	Human	Esophagus	ESCC	6.22e-09	3.37e-02	0.1236
8936	WASF1	P24T-E	Human	Esophagus	ESCC	1.79e-02	5.57e-02	0.1287
8936	WASF1	P26T-E	Human	Esophagus	ESCC	1.10e-09	2.20e-01	0.1276
8936	WASF1	P27T-E	Human	Esophagus	ESCC	9.32e-16	2.49e-01	0.1055
8936	WASF1	P28T-E	Human	Esophagus	ESCC	1.28e-03	7.44e-02	0.1149
8936	WASF1	P30T-E	Human	Esophagus	ESCC	6.19e-31	1.29e+00	0.137
8936	WASF1	P31T-E	Human	Esophagus	ESCC	2.04e-04	1.84e-01	0.1251

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

∗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:00166019	Esophagus	ESCC	Rac protein signal transduction	33/8552	42/18723	1.35e-05	1.23e-04	33
GO:003083819	Esophagus	ESCC	positive regulation of actin filament polymerization	66/8552	99/18723	1.96e-05	1.72e-04	66
GO:000815420	Esophagus	ESCC	actin polymerization or depolymerization	130/8552	218/18723	2.19e-05	1.88e-04	130
GO:00991114	Esophagus	ESCC	microtubule-based transport	115/8552	190/18723	2.54e-05	2.15e-04	115
GO:005165411	Esophagus	ESCC	establishment of mitochondrion localization	24/8552	29/18723	4.50e-05	3.55e-04	24
GO:000689818	Esophagus	ESCC	receptor-mediated endocytosis	142/8552	244/18723	5.22e-05	4.05e-04	142
GO:0030041110	Esophagus	ESCC	actin filament polymerization	114/8552	191/18723	6.46e-05	4.92e-04	114
GO:000806419	Esophagus	ESCC	regulation of actin polymerization or depolymerization	112/8552	188/18723	8.31e-05	6.06e-04	112
GO:199009017	Esophagus	ESCC	cellular response to nerve growth factor stimulus	38/8552	53/18723	1.10e-04	7.69e-04	38
GO:003083218	Esophagus	ESCC	regulation of actin filament length	112/8552	189/18723	1.13e-04	7.85e-04	112
GO:003083320	Esophagus	ESCC	regulation of actin filament polymerization	103/8552	172/18723	1.19e-04	8.15e-04	103
GO:00705848	Esophagus	ESCC	mitochondrion morphogenesis	18/8552	21/18723	1.81e-04	1.16e-03	18
GO:199008916	Esophagus	ESCC	response to nerve growth factor	39/8552	56/18723	2.44e-04	1.51e-03	39
GO:00346431	Esophagus	ESCC	establishment of mitochondrion localization, microtubule-mediated	21/8552	26/18723	2.69e-04	1.63e-03	21
GO:00474971	Esophagus	ESCC	mitochondrion transport along microtubule	21/8552	26/18723	2.69e-04	1.63e-03	21
GO:00516463	Esophagus	ESCC	mitochondrion localization	35/8552	50/18723	4.33e-04	2.44e-03	35
GO:003431415	Esophagus	ESCC	Arp2/3 complex-mediated actin nucleation	28/8552	39/18723	8.57e-04	4.40e-03	28
GO:006056010	Esophagus	ESCC	developmental growth involved in morphogenesis	131/8552	234/18723	9.28e-04	4.73e-03	131
GO:00726735	Esophagus	ESCC	lamellipodium morphogenesis	14/8552	17/18723	2.22e-03	9.78e-03	14
GO:00343156	Esophagus	ESCC	regulation of Arp2/3 complex-mediated actin nucleation	16/8552	21/18723	4.47e-03	1.76e-02	16

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa05130211	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa05100211	Esophagus	ESCC	Bacterial invasion of epithelial cells	59/4205	77/8465	1.05e-06	6.76e-06	3.46e-06	59
hsa0452030	Esophagus	ESCC	Adherens junction	69/4205	93/8465	1.08e-06	6.83e-06	3.50e-06	69
hsa0466620	Esophagus	ESCC	Fc gamma R-mediated phagocytosis	63/4205	97/8465	1.63e-03	4.89e-03	2.50e-03	63
hsa0481028	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa052319	Esophagus	ESCC	Choline metabolism in cancer	61/4205	98/8465	7.97e-03	1.92e-02	9.84e-03	61
hsa05131310	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa05130310	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa05100310	Esophagus	ESCC	Bacterial invasion of epithelial cells	59/4205	77/8465	1.05e-06	6.76e-06	3.46e-06	59
hsa04520114	Esophagus	ESCC	Adherens junction	69/4205	93/8465	1.08e-06	6.83e-06	3.50e-06	69
hsa04666110	Esophagus	ESCC	Fc gamma R-mediated phagocytosis	63/4205	97/8465	1.63e-03	4.89e-03	2.50e-03	63
hsa04810112	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa0523114	Esophagus	ESCC	Choline metabolism in cancer	61/4205	98/8465	7.97e-03	1.92e-02	9.84e-03	61
hsa0513042	Liver	HCC	Pathogenic Escherichia coli infection	129/4020	197/8465	2.02e-07	2.50e-06	1.39e-06	129
hsa0452042	Liver	HCC	Adherens junction	68/4020	93/8465	3.99e-07	4.46e-06	2.48e-06	68
hsa0513142	Liver	HCC	Shigellosis	150/4020	247/8465	1.53e-05	1.04e-04	5.81e-05	150
hsa0481041	Liver	HCC	Regulation of actin cytoskeleton	134/4020	229/8465	4.48e-04	1.94e-03	1.08e-03	134
hsa0510022	Liver	HCC	Bacterial invasion of epithelial cells	51/4020	77/8465	6.67e-04	2.72e-03	1.52e-03	51
hsa0466610	Liver	HCC	Fc gamma R-mediated phagocytosis	58/4020	97/8465	9.65e-03	2.52e-02	1.40e-02	58

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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

WASF1

SNV

Missense_Mutation

c.692N>A

p.Pro231Gln

p.P231Q

Q92558

protein_coding

deleterious(0.01)

benign(0.401)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WASF1

SNV

Missense_Mutation

novel

c.664C>A

p.His222Asn

p.H222N

Q92558

protein_coding

deleterious(0.02)

benign(0.005)

TCGA-AC-A8OP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WASF1

SNV

Missense_Mutation

c.1384G>A

p.Ala462Thr

p.A462T

Q92558

protein_coding

tolerated_low_confidence(0.58)

benign(0.007)

TCGA-AO-A0J2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

WASF1

SNV

Missense_Mutation

c.766N>T

p.Pro256Ser

p.P256S

Q92558

protein_coding

deleterious(0.05)

probably_damaging(0.992)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

WASF1

SNV

Missense_Mutation

c.232G>C

p.Val78Leu

p.V78L

Q92558

protein_coding

deleterious(0)

benign(0.001)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

WASF1

SNV

Missense_Mutation

c.797N>C

p.Arg266Thr

p.R266T

Q92558

protein_coding

tolerated(0.27)

probably_damaging(0.95)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

WASF1

SNV

Missense_Mutation

c.250N>A

p.Asp84Asn

p.D84N

Q92558

protein_coding

deleterious(0)

probably_damaging(0.962)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

WASF1

SNV

Missense_Mutation

c.777N>C

p.Gln259His

p.Q259H

Q92558

protein_coding

tolerated(0.12)

probably_damaging(0.969)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

WASF1

SNV

Missense_Mutation

novel

c.319N>G

p.Gln107Glu

p.Q107E

Q92558

protein_coding

deleterious(0)

possibly_damaging(0.784)

TCGA-ZJ-AAXU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

WASF1

SNV

Missense_Mutation

c.1390N>T

p.Gly464Cys

p.G464C

Q92558

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.996)

TCGA-A6-6780-01

Colorectum

colon adenocarcinoma

Male

>=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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