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: WRN

Gene summary for WRN

Gene summary.

Gene information	Species	Human
	Gene symbol	WRN
	Gene ID	7486
	Gene name	WRN RecQ like helicase
	Gene Alias	RECQ3
	Cytomap	8p12
	Gene Type	protein-coding
	GO ID	GO:0000723
	UniProtAcc	Q14191

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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
7486	WRN	CCI_2	Human	Cervix	CC	4.58e-05	9.44e-01	0.5249
7486	WRN	CCI_3	Human	Cervix	CC	2.40e-10	7.16e-01	0.516
7486	WRN	HTA12-23-1	Human	Pancreas	PDAC	1.24e-03	4.83e-01	0.3405
7486	WRN	HTA12-25-1	Human	Pancreas	PDAC	2.95e-02	3.27e-01	0.313
7486	WRN	HTA12-26-1	Human	Pancreas	PDAC	2.64e-12	6.07e-01	0.3728
7486	WRN	HTA12-29-1	Human	Pancreas	PDAC	2.20e-26	6.13e-01	0.3722
7486	WRN	048752_1579-all-cells	Human	Prostate	BPH	2.12e-22	5.43e-01	0.1008
7486	WRN	052095_1628-all-cells	Human	Prostate	BPH	8.93e-21	5.34e-01	0.1032
7486	WRN	052097_1595-all-cells	Human	Prostate	BPH	4.63e-20	5.95e-01	0.0972
7486	WRN	052099_1652-all-cells	Human	Prostate	BPH	3.74e-09	4.32e-01	0.1038

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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
Prostate		BPH: Benign Prostatic Hyperplasia

∗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:000697910	Cervix	CC	response to oxidative stress	102/2311	446/18723	2.99e-10	4.36e-08	102
GO:007149610	Cervix	CC	cellular response to external stimulus	78/2311	320/18723	1.82e-09	1.98e-07	78
GO:00345048	Cervix	CC	protein localization to nucleus	68/2311	290/18723	9.91e-08	5.25e-06	68
GO:00075689	Cervix	CC	aging	75/2311	339/18723	2.75e-07	1.13e-05	75
GO:00316689	Cervix	CC	cellular response to extracellular stimulus	59/2311	246/18723	3.03e-07	1.24e-05	59
GO:003166710	Cervix	CC	response to nutrient levels	92/2311	474/18723	5.80e-06	1.42e-04	92
GO:00712148	Cervix	CC	cellular response to abiotic stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:01040048	Cervix	CC	cellular response to environmental stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:00092678	Cervix	CC	cellular response to starvation	39/2311	156/18723	1.04e-05	2.32e-04	39
GO:00425948	Cervix	CC	response to starvation	46/2311	197/18723	1.24e-05	2.59e-04	46
GO:00316698	Cervix	CC	cellular response to nutrient levels	49/2311	215/18723	1.32e-05	2.68e-04	49
GO:00075695	Cervix	CC	cell aging	34/2311	132/18723	1.92e-05	3.53e-04	34
GO:00714798	Cervix	CC	cellular response to ionizing radiation	22/2311	72/18723	3.47e-05	5.60e-04	22
GO:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86
GO:00714786	Cervix	CC	cellular response to radiation	41/2311	186/18723	1.41e-04	1.71e-03	41
GO:00102126	Cervix	CC	response to ionizing radiation	34/2311	148/18723	2.23e-04	2.53e-03	34
GO:00094112	Cervix	CC	response to UV	33/2311	149/18723	5.51e-04	5.29e-03	33
GO:00510528	Cervix	CC	regulation of DNA metabolic process	65/2311	359/18723	9.25e-04	7.84e-03	65
GO:00062602	Cervix	CC	DNA replication	48/2311	260/18723	2.70e-03	1.85e-02	48
GO:00323923	Cervix	CC	DNA geometric change	21/2311	90/18723	2.71e-03	1.85e-02	21

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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

WRN

SNV

Missense_Mutation

novel

c.1940N>T

p.Ser647Leu

p.S647L

Q14191

protein_coding

tolerated(0.09)

benign(0.022)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

WRN

SNV

Missense_Mutation

novel

c.749N>G

p.Met250Arg

p.M250R

Q14191

protein_coding

deleterious(0)

benign(0.124)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

WRN

SNV

Missense_Mutation

novel

c.2260C>G

p.Leu754Val

p.L754V

Q14191

protein_coding

deleterious(0)

possibly_damaging(0.77)

TCGA-AC-A2B8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

chemo

WRN

SNV

Missense_Mutation

novel

c.1335N>C

p.Glu445Asp

p.E445D

Q14191

protein_coding

tolerated(0.1)

benign(0.216)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WRN

SNV

Missense_Mutation

novel

c.1416N>C

p.Glu472Asp

p.E472D

Q14191

protein_coding

tolerated(0.21)

benign(0.174)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WRN

SNV

Missense_Mutation

c.1475N>A

p.Ser492Tyr

p.S492Y

Q14191

protein_coding

deleterious(0)

possibly_damaging(0.744)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WRN

SNV

Missense_Mutation

rs752650803

c.1988N>T

p.Thr663Met

p.T663M

Q14191

protein_coding

deleterious(0)

probably_damaging(0.912)

TCGA-D8-A1Y3-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicine+cyclophosphamide

WRN

SNV

Missense_Mutation

c.2122N>G

p.Ser708Ala

p.S708A

Q14191

protein_coding

deleterious(0.01)

possibly_damaging(0.681)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WRN

deletion

Frame_Shift_Del

rs778872619

c.3376delN

p.Ser1128ValfsTer34

p.S1128Vfs*34

Q14191

protein_coding

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

WRN

SNV

Missense_Mutation

rs756575284

c.197N>T

p.Ser66Leu

p.S66L

Q14191

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

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
7486	WRN	CLINICALLY ACTIONABLE, DNA REPAIR, ENZYME		NSC-7387	CHEMBL119878
7486	WRN	CLINICALLY ACTIONABLE, DNA REPAIR, ENZYME		GNF-PF-4459	CHEMBL585502
7486	WRN	CLINICALLY ACTIONABLE, DNA REPAIR, ENZYME		SJ000001516	CHEMBL592316
7486	WRN	CLINICALLY ACTIONABLE, DNA REPAIR, ENZYME		NSC-11437	CHEMBL1814509
7486	WRN	CLINICALLY ACTIONABLE, DNA REPAIR, ENZYME		TCMDC-123916	CHEMBL493863
7486	WRN	CLINICALLY ACTIONABLE, DNA REPAIR, ENZYME		NSC-720622	CHEMBL1287980
7486	WRN	CLINICALLY ACTIONABLE, DNA REPAIR, ENZYME		UREA	UREA	17312972
7486	WRN	CLINICALLY ACTIONABLE, DNA REPAIR, ENZYME		NSC-348401	CHEMBL515505
7486	WRN	CLINICALLY ACTIONABLE, DNA REPAIR, ENZYME		QUERCETIN DIHYDRATE	QUERCETIN DIHYDRATE
7486	WRN	CLINICALLY ACTIONABLE, DNA REPAIR, ENZYME		NANAOMYCIN	NANAOMYCIN

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