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: WAC

Gene summary for WAC

Gene summary.

Gene information	Species	Human
	Gene symbol	WAC
	Gene ID	51322
	Gene name	WW domain containing adaptor with coiled-coil
	Gene Alias	BM-016
	Cytomap	10p12.1
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	Q9BTA9

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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
51322	WAC	CA_HPV_1	Human	Cervix	CC	1.14e-06	-6.65e-02	0.0264
51322	WAC	CCI_1	Human	Cervix	CC	1.16e-04	8.37e-01	0.528
51322	WAC	CCI_2	Human	Cervix	CC	1.16e-07	1.19e+00	0.5249
51322	WAC	CCI_3	Human	Cervix	CC	1.36e-08	8.37e-01	0.516
51322	WAC	L1	Human	Cervix	CC	2.71e-03	-2.29e-01	0.0802
51322	WAC	HTA11_3410_2000001011	Human	Colorectum	AD	1.13e-21	-6.27e-01	0.0155
51322	WAC	HTA11_1938_2000001011	Human	Colorectum	AD	6.84e-04	4.80e-01	-0.0811
51322	WAC	HTA11_347_2000001011	Human	Colorectum	AD	4.17e-05	3.81e-01	-0.1954
51322	WAC	HTA11_99999965062_69753	Human	Colorectum	MSI-H	2.63e-04	8.29e-01	0.3487
51322	WAC	HTA11_99999965104_69814	Human	Colorectum	MSS	5.25e-08	5.98e-01	0.281
51322	WAC	HTA11_99999974143_84620	Human	Colorectum	MSS	6.48e-06	-4.08e-01	0.3005
51322	WAC	A001-C-207	Human	Colorectum	FAP	2.54e-04	-1.50e-01	0.1278
51322	WAC	A015-C-203	Human	Colorectum	FAP	4.61e-34	-3.28e-01	-0.1294
51322	WAC	A015-C-204	Human	Colorectum	FAP	1.28e-07	-2.69e-01	-0.0228
51322	WAC	A014-C-040	Human	Colorectum	FAP	1.45e-06	-3.98e-01	-0.1184
51322	WAC	A002-C-201	Human	Colorectum	FAP	4.30e-14	-2.96e-01	0.0324
51322	WAC	A002-C-203	Human	Colorectum	FAP	1.22e-03	-1.48e-01	0.2786
51322	WAC	A001-C-119	Human	Colorectum	FAP	2.35e-05	-2.70e-01	-0.1557
51322	WAC	A001-C-108	Human	Colorectum	FAP	7.60e-15	-2.23e-01	-0.0272
51322	WAC	A002-C-205	Human	Colorectum	FAP	1.13e-27	-3.87e-01	-0.1236

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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
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
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:00335234	Esophagus	ESCC	histone H2B ubiquitination	12/8552	12/18723	8.21e-05	6.01e-04	12
GO:00319294	Esophagus	ESCC	TOR signaling	79/8552	126/18723	8.57e-05	6.21e-04	79
GO:004477312	Esophagus	ESCC	mitotic DNA damage checkpoint	54/8552	81/18723	1.09e-04	7.64e-04	54
GO:0045861111	Esophagus	ESCC	negative regulation of proteolysis	195/8552	351/18723	1.13e-04	7.85e-04	195
GO:003157116	Esophagus	ESCC	mitotic G1 DNA damage checkpoint	24/8552	30/18723	1.27e-04	8.67e-04	24
GO:00447745	Esophagus	ESCC	mitotic DNA integrity checkpoint	56/8552	85/18723	1.34e-04	9.09e-04	56
GO:1903051110	Esophagus	ESCC	negative regulation of proteolysis involved in cellular protein catabolic process	44/8552	64/18723	1.59e-04	1.05e-03	44
GO:004481915	Esophagus	ESCC	mitotic G1/S transition checkpoint	24/8552	31/18723	3.19e-04	1.89e-03	24
GO:00162394	Esophagus	ESCC	positive regulation of macroautophagy	41/8552	63/18723	1.48e-03	6.99e-03	41
GO:00320061	Esophagus	ESCC	regulation of TOR signaling	63/8552	104/18723	1.55e-03	7.29e-03	63
GO:19017999	Esophagus	ESCC	negative regulation of proteasomal protein catabolic process	33/8552	49/18723	1.80e-03	8.26e-03	33
GO:200004513	Esophagus	ESCC	regulation of G1/S transition of mitotic cell cycle	82/8552	142/18723	2.49e-03	1.08e-02	82
GO:190280613	Esophagus	ESCC	regulation of cell cycle G1/S phase transition	95/8552	168/18723	2.91e-03	1.22e-02	95
GO:00320082	Esophagus	ESCC	positive regulation of TOR signaling	31/8552	47/18723	4.01e-03	1.62e-02	31
GO:00098967	Liver	NAFLD	positive regulation of catabolic process	108/1882	492/18723	2.68e-15	3.14e-12	108
GO:00431617	Liver	NAFLD	proteasome-mediated ubiquitin-dependent protein catabolic process	91/1882	412/18723	3.00e-13	1.75e-10	91
GO:00313317	Liver	NAFLD	positive regulation of cellular catabolic process	92/1882	427/18723	1.01e-12	4.91e-10	92
GO:00104987	Liver	NAFLD	proteasomal protein catabolic process	101/1882	490/18723	1.35e-12	6.09e-10	101
GO:00421767	Liver	NAFLD	regulation of protein catabolic process	83/1882	391/18723	2.94e-11	1.01e-08	83
GO:00165703	Liver	NAFLD	histone modification	90/1882	463/18723	5.74e-10	1.28e-07	90

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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

WAC

SNV

Missense_Mutation

c.306C>G

p.His102Gln

p.H102Q

Q9BTA9

protein_coding

tolerated(0.13)

benign(0.063)

TCGA-A2-A3XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

WAC

SNV

Missense_Mutation

c.1142N>C

p.Val381Ala

p.V381A

Q9BTA9

protein_coding

deleterious(0.03)

possibly_damaging(0.503)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WAC

SNV

Missense_Mutation

novel

c.1798N>A

p.Glu600Lys

p.E600K

Q9BTA9

protein_coding

tolerated(0.09)

probably_damaging(0.972)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WAC

SNV

Missense_Mutation

novel

c.16A>G

p.Arg6Gly

p.R6G

Q9BTA9

protein_coding

deleterious(0.04)

benign(0)

TCGA-AQ-A7U7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Targeted Molecular therapy

rituximab

WAC

SNV

Missense_Mutation

rs200723559

c.1586N>G

p.Asn529Ser

p.N529S

Q9BTA9

protein_coding

tolerated(0.13)

possibly_damaging(0.584)

TCGA-BH-A0E0-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

WAC

SNV

Missense_Mutation

rs750794271

c.376N>C

p.Asp126His

p.D126H

Q9BTA9

protein_coding

deleterious(0.01)

probably_damaging(0.995)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WAC

SNV

Missense_Mutation

c.1887N>C

p.Leu629Phe

p.L629F

Q9BTA9

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

WAC

SNV

Missense_Mutation

c.1595C>A

p.Ser532Tyr

p.S532Y

Q9BTA9

protein_coding

tolerated(1)

possibly_damaging(0.598)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

WAC

insertion

Frame_Shift_Ins

novel

c.1537_1538insT

p.Arg513LeufsTer8

p.R513Lfs*8

Q9BTA9

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

WAC

insertion

Frame_Shift_Ins

novel

c.1538_1539insAGGGAGAATTATTAATCATATCCCCTCACCCCACCAA

p.Ser514GlyfsTer19

p.S514Gfs*19

Q9BTA9

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

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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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