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: WDFY1

Gene summary for WDFY1

Gene summary.

Gene information	Species	Human
	Gene symbol	WDFY1
	Gene ID	57590
	Gene name	WD repeat and FYVE domain containing 1
	Gene Alias	FENS-1
	Cytomap	2q36.1
	Gene Type	protein-coding
	GO ID	GO:0002221
	UniProtAcc	A0A024R488

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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
57590	WDFY1	LZE4T	Human	Esophagus	ESCC	3.27e-09	2.72e-01	0.0811
57590	WDFY1	LZE7T	Human	Esophagus	ESCC	8.23e-06	1.94e-01	0.0667
57590	WDFY1	LZE20T	Human	Esophagus	ESCC	1.26e-04	1.36e-01	0.0662
57590	WDFY1	LZE24T	Human	Esophagus	ESCC	2.57e-10	3.31e-01	0.0596
57590	WDFY1	P1T-E	Human	Esophagus	ESCC	1.72e-04	2.58e-01	0.0875
57590	WDFY1	P2T-E	Human	Esophagus	ESCC	2.24e-17	4.35e-01	0.1177
57590	WDFY1	P4T-E	Human	Esophagus	ESCC	2.08e-16	3.03e-01	0.1323
57590	WDFY1	P5T-E	Human	Esophagus	ESCC	3.26e-11	3.47e-01	0.1327
57590	WDFY1	P8T-E	Human	Esophagus	ESCC	6.55e-11	2.81e-01	0.0889
57590	WDFY1	P9T-E	Human	Esophagus	ESCC	5.58e-08	2.42e-01	0.1131
57590	WDFY1	P10T-E	Human	Esophagus	ESCC	3.90e-28	5.25e-01	0.116
57590	WDFY1	P11T-E	Human	Esophagus	ESCC	6.66e-13	5.24e-01	0.1426
57590	WDFY1	P12T-E	Human	Esophagus	ESCC	2.74e-25	5.67e-01	0.1122
57590	WDFY1	P15T-E	Human	Esophagus	ESCC	7.62e-28	6.29e-01	0.1149
57590	WDFY1	P16T-E	Human	Esophagus	ESCC	2.92e-22	4.13e-01	0.1153
57590	WDFY1	P17T-E	Human	Esophagus	ESCC	5.38e-05	3.70e-01	0.1278
57590	WDFY1	P20T-E	Human	Esophagus	ESCC	9.78e-17	4.06e-01	0.1124
57590	WDFY1	P21T-E	Human	Esophagus	ESCC	1.73e-16	3.24e-01	0.1617
57590	WDFY1	P22T-E	Human	Esophagus	ESCC	3.92e-11	2.52e-01	0.1236
57590	WDFY1	P23T-E	Human	Esophagus	ESCC	1.28e-13	3.34e-01	0.108

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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
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
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:00022211	Liver	HCC	pattern recognition receptor signaling pathway	107/7958	172/18723	1.37e-07	2.58e-06	107
GO:0002224	Liver	HCC	toll-like receptor signaling pathway	67/7958	121/18723	2.87e-03	1.34e-02	67
GO:00622072	Liver	HCC	regulation of pattern recognition receptor signaling pathway	59/7958	105/18723	3.18e-03	1.47e-02	59
GO:00022214	Oral cavity	OSCC	pattern recognition receptor signaling pathway	95/7305	172/18723	1.11e-05	1.15e-04	95
GO:00622076	Oral cavity	OSCC	regulation of pattern recognition receptor signaling pathway	56/7305	105/18723	1.99e-03	9.23e-03	56
GO:00022243	Oral cavity	OSCC	toll-like receptor signaling pathway	63/7305	121/18723	2.36e-03	1.04e-02	63
GO:00027646	Oral cavity	OSCC	immune response-regulating signaling pathway	212/7305	468/18723	2.93e-03	1.27e-02	212
GO:00622087	Oral cavity	OSCC	positive regulation of pattern recognition receptor signaling pathway	26/7305	44/18723	5.49e-03	2.13e-02	26
GO:00341424	Oral cavity	OSCC	toll-like receptor 4 signaling pathway	25/7305	43/18723	8.52e-03	3.09e-02	25
GO:000276413	Oral cavity	EOLP	immune response-regulating signaling pathway	108/2218	468/18723	4.04e-12	7.34e-10	108
GO:000222113	Oral cavity	EOLP	pattern recognition receptor signaling pathway	45/2218	172/18723	1.82e-07	5.82e-06	45
GO:000222411	Oral cavity	EOLP	toll-like receptor signaling pathway	31/2218	121/18723	2.21e-05	3.37e-04	31
GO:006220713	Oral cavity	EOLP	regulation of pattern recognition receptor signaling pathway	28/2218	105/18723	2.46e-05	3.65e-04	28
GO:00341211	Oral cavity	EOLP	regulation of toll-like receptor signaling pathway	19/2218	75/18723	9.43e-04	7.15e-03	19
GO:006220813	Oral cavity	EOLP	positive regulation of pattern recognition receptor signaling pathway	13/2218	44/18723	1.30e-03	9.21e-03	13
GO:006220822	Oral cavity	NEOLP	positive regulation of pattern recognition receptor signaling pathway	14/2005	44/18723	1.28e-04	1.49e-03	14
GO:000222121	Oral cavity	NEOLP	pattern recognition receptor signaling pathway	35/2005	172/18723	1.38e-04	1.60e-03	35
GO:000276422	Oral cavity	NEOLP	immune response-regulating signaling pathway	74/2005	468/18723	3.90e-04	3.63e-03	74
GO:00022242	Oral cavity	NEOLP	toll-like receptor signaling pathway	24/2005	121/18723	2.08e-03	1.38e-02	24
GO:0034138	Oral cavity	NEOLP	toll-like receptor 3 signaling pathway	6/2005	16/18723	4.64e-03	2.56e-02	6

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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

WDFY1

SNV

Missense_Mutation

rs747629496

c.986N>A

p.Arg329His

p.R329H

Q8IWB7

protein_coding

deleterious(0.03)

probably_damaging(0.998)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WDFY1

SNV

Missense_Mutation

c.161G>A

p.Arg54Lys

p.R54K

Q8IWB7

protein_coding

deleterious(0.04)

possibly_damaging(0.815)

TCGA-AR-A1AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

WDFY1

SNV

Missense_Mutation

novel

c.955N>A

p.Gln319Lys

p.Q319K

Q8IWB7

protein_coding

tolerated(1)

benign(0)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

WDFY1

insertion

Frame_Shift_Ins

novel

c.528_529insATATATATATATGCGAAATTTAGAG

p.Gly177IlefsTer17

p.G177Ifs*17

Q8IWB7

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WDFY1

SNV

Missense_Mutation

c.938N>C

p.His313Pro

p.H313P

Q8IWB7

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WDFY1

SNV

Missense_Mutation

c.1186A>C

p.Thr396Pro

p.T396P

Q8IWB7

protein_coding

deleterious(0.02)

benign(0.221)

TCGA-G4-6304-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

WDFY1

SNV

Missense_Mutation

novel

c.796N>C

p.Ile266Leu

p.I266L

Q8IWB7

protein_coding

tolerated(0.76)

benign(0.021)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

WDFY1

SNV

Missense_Mutation

rs368104342

c.1067G>A

p.Arg356Gln

p.R356Q

Q8IWB7

protein_coding

tolerated(0.12)

probably_damaging(0.992)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

WDFY1

SNV

Missense_Mutation

novel

c.656C>A

p.Ser219Tyr

p.S219Y

Q8IWB7

protein_coding

tolerated(1)

possibly_damaging(0.857)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

WDFY1

SNV

Missense_Mutation

novel

c.242G>T

p.Arg81Ile

p.R81I

Q8IWB7

protein_coding

deleterious(0.01)

probably_damaging(0.986)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

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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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