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: WTAP

Gene summary for WTAP

Gene summary.

Gene information	Species	Human
	Gene symbol	WTAP
	Gene ID	9589
	Gene name	WT1 associated protein
	Gene Alias	Mum2
	Cytomap	6q25.3
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	Q15007

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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
9589	WTAP	GSM4909285	Human	Breast	IDC	4.20e-09	-4.47e-01	0.21
9589	WTAP	GSM4909286	Human	Breast	IDC	2.78e-08	-2.13e-01	0.1081
9589	WTAP	GSM4909288	Human	Breast	IDC	1.46e-03	-4.52e-01	0.0988
9589	WTAP	GSM4909291	Human	Breast	IDC	1.46e-14	-6.05e-01	0.1753
9589	WTAP	GSM4909292	Human	Breast	IDC	2.24e-05	-7.57e-01	0.1236
9589	WTAP	GSM4909293	Human	Breast	IDC	7.75e-04	-2.96e-01	0.1581
9589	WTAP	GSM4909294	Human	Breast	IDC	3.32e-12	-5.67e-01	0.2022
9589	WTAP	GSM4909296	Human	Breast	IDC	3.72e-36	-7.32e-01	0.1524
9589	WTAP	GSM4909297	Human	Breast	IDC	9.34e-19	-3.45e-01	0.1517
9589	WTAP	GSM4909298	Human	Breast	IDC	4.93e-07	-3.86e-01	0.1551
9589	WTAP	GSM4909299	Human	Breast	IDC	3.74e-04	-3.22e-01	0.035
9589	WTAP	GSM4909301	Human	Breast	IDC	5.13e-08	-4.64e-01	0.1577
9589	WTAP	GSM4909302	Human	Breast	IDC	5.26e-25	-5.93e-01	0.1545
9589	WTAP	GSM4909304	Human	Breast	IDC	2.32e-06	-4.15e-01	0.1636
9589	WTAP	GSM4909305	Human	Breast	IDC	4.28e-02	-2.33e-01	0.0436
9589	WTAP	GSM4909306	Human	Breast	IDC	4.09e-10	-4.35e-01	0.1564
9589	WTAP	GSM4909307	Human	Breast	IDC	2.37e-17	-5.72e-01	0.1569
9589	WTAP	GSM4909308	Human	Breast	IDC	8.16e-11	-4.18e-01	0.158
9589	WTAP	GSM4909309	Human	Breast	IDC	1.21e-13	-4.67e-01	0.0483
9589	WTAP	GSM4909311	Human	Breast	IDC	1.47e-40	-7.04e-01	0.1534

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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:000838024	Breast	DCIS	RNA splicing	73/1390	434/18723	3.05e-11	5.08e-09	73
GO:004348424	Breast	DCIS	regulation of RNA splicing	36/1390	148/18723	1.40e-10	1.69e-08	36
GO:000037524	Breast	DCIS	RNA splicing, via transesterification reactions	58/1390	324/18723	2.89e-10	3.34e-08	58
GO:000037724	Breast	DCIS	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	57/1390	320/18723	5.01e-10	5.35e-08	57
GO:000039824	Breast	DCIS	mRNA splicing, via spliceosome	57/1390	320/18723	5.01e-10	5.35e-08	57
GO:004802424	Breast	DCIS	regulation of mRNA splicing, via spliceosome	23/1390	101/18723	1.02e-06	4.04e-05	23
GO:005068423	Breast	DCIS	regulation of mRNA processing	24/1390	137/18723	6.71e-05	1.33e-03	24
GO:190331123	Breast	DCIS	regulation of mRNA metabolic process	40/1390	288/18723	9.26e-05	1.71e-03	40
GO:000038123	Breast	DCIS	regulation of alternative mRNA splicing, via spliceosome	13/1390	60/18723	3.78e-04	5.27e-03	13
GO:000038023	Breast	DCIS	alternative mRNA splicing, via spliceosome	15/1390	77/18723	4.70e-04	6.20e-03	15
GO:000838016	Endometrium	AEH	RNA splicing	111/2100	434/18723	2.42e-17	1.12e-14	111
GO:004348416	Endometrium	AEH	regulation of RNA splicing	55/2100	148/18723	1.28e-16	5.49e-14	55
GO:000037515	Endometrium	AEH	RNA splicing, via transesterification reactions	88/2100	324/18723	1.11e-15	3.91e-13	88
GO:000037715	Endometrium	AEH	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	87/2100	320/18723	1.51e-15	4.78e-13	87
GO:000039815	Endometrium	AEH	mRNA splicing, via spliceosome	87/2100	320/18723	1.51e-15	4.78e-13	87
GO:004802416	Endometrium	AEH	regulation of mRNA splicing, via spliceosome	40/2100	101/18723	1.56e-13	4.27e-11	40
GO:190331110	Endometrium	AEH	regulation of mRNA metabolic process	77/2100	288/18723	1.69e-13	4.40e-11	77
GO:005068410	Endometrium	AEH	regulation of mRNA processing	42/2100	137/18723	6.05e-10	5.67e-08	42
GO:00003809	Endometrium	AEH	alternative mRNA splicing, via spliceosome	26/2100	77/18723	1.28e-07	5.97e-06	26
GO:00003819	Endometrium	AEH	regulation of alternative mRNA splicing, via spliceosome	20/2100	60/18723	4.46e-06	1.17e-04	20

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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

WTAP

SNV

Missense_Mutation

c.152N>C

p.Asp51Ala

p.D51A

Q15007

protein_coding

tolerated(0.07)

possibly_damaging(0.78)

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

WTAP

SNV

Missense_Mutation

c.236G>A

p.Arg79Gln

p.R79Q

Q15007

protein_coding

deleterious(0.04)

benign(0.38)

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

WTAP

SNV

Missense_Mutation

rs375840138

c.1001N>T

p.Ala334Val

p.A334V

Q15007

protein_coding

tolerated_low_confidence(0.33)

benign(0)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

WTAP

SNV

Missense_Mutation

c.485N>C

p.Arg162Pro

p.R162P

Q15007

protein_coding

deleterious(0)

possibly_damaging(0.899)

TCGA-D8-A1XB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

WTAP

SNV

Missense_Mutation

rs369657864

c.932A>G

p.Asn311Ser

p.N311S

Q15007

protein_coding

tolerated_low_confidence(0.51)

benign(0.025)

TCGA-XX-A89A-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WTAP

insertion

Nonsense_Mutation

novel

c.573_574insCCAACTGCACTCCAGCCTGGGCTACAGAGTGAGACTCCATCCTAA

p.Lys191_Lys192insProThrAlaLeuGlnProGlyLeuGlnSerGluThrProSerTer

p.K191_K192insPTALQPGLQSETPS*

Q15007

protein_coding

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

WTAP

insertion

Frame_Shift_Ins

novel

c.929_930insCTTGCTTTGTGGCAGGCAC

p.Asn311LeufsTer7

p.N311Lfs*7

Q15007

protein_coding

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WTAP

insertion

Frame_Shift_Ins

novel

c.931_932insAAGAAACATTTTTCAATGTT

p.Asn311LysfsTer26

p.N311Kfs*26

Q15007

protein_coding

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WTAP

SNV

Missense_Mutation

novel

c.1082A>G

p.Asp361Gly

p.D361G

Q15007

protein_coding

deleterious_low_confidence(0.01)

benign(0.084)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WTAP

SNV

Missense_Mutation

c.448N>C

p.Asp150His

p.D150H

Q15007

protein_coding

deleterious(0.03)

probably_damaging(0.98)

TCGA-DG-A2KK-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

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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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