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: WDR45B

Gene summary for WDR45B

Gene summary.

Gene information	Species	Human
	Gene symbol	WDR45B
	Gene ID	56270
	Gene name	WD repeat domain 45B
	Gene Alias	NEDSBAS
	Cytomap	17q25.3
	Gene Type	protein-coding
	GO ID	GO:0000045
	UniProtAcc	A0A024R8U4

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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
56270	WDR45B	GSM4909282	Human	Breast	IDC	2.26e-07	4.22e-01	-0.0288
56270	WDR45B	GSM4909293	Human	Breast	IDC	1.96e-04	2.79e-01	0.1581
56270	WDR45B	GSM4909294	Human	Breast	IDC	4.04e-03	-1.93e-01	0.2022
56270	WDR45B	GSM4909296	Human	Breast	IDC	6.07e-15	-3.46e-01	0.1524
56270	WDR45B	GSM4909297	Human	Breast	IDC	1.18e-12	-2.87e-01	0.1517
56270	WDR45B	GSM4909309	Human	Breast	IDC	1.90e-02	-2.08e-01	0.0483
56270	WDR45B	GSM4909311	Human	Breast	IDC	7.33e-25	-3.30e-01	0.1534
56270	WDR45B	GSM4909312	Human	Breast	IDC	3.77e-13	-2.24e-01	0.1552
56270	WDR45B	GSM4909319	Human	Breast	IDC	6.62e-29	-2.86e-01	0.1563
56270	WDR45B	GSM4909320	Human	Breast	IDC	4.19e-09	2.37e-01	0.1575
56270	WDR45B	GSM4909321	Human	Breast	IDC	4.94e-10	-5.86e-02	0.1559
56270	WDR45B	ctrl6	Human	Breast	Precancer	1.30e-05	5.05e-01	-0.0061
56270	WDR45B	brca3	Human	Breast	Precancer	6.01e-03	3.23e-01	-0.0263
56270	WDR45B	NCCBC14	Human	Breast	DCIS	4.77e-06	-1.96e-01	0.2021
56270	WDR45B	NCCBC3	Human	Breast	DCIS	3.93e-05	-2.06e-01	0.1198
56270	WDR45B	NCCBC5	Human	Breast	DCIS	1.28e-11	-1.61e-01	0.2046
56270	WDR45B	P1	Human	Breast	IDC	4.96e-17	-2.97e-01	0.1527
56270	WDR45B	P2	Human	Breast	IDC	8.96e-09	4.39e-01	0.21
56270	WDR45B	DCIS2	Human	Breast	DCIS	8.48e-46	1.45e-01	0.0085
56270	WDR45B	LZE2T	Human	Esophagus	ESCC	2.23e-03	4.72e-01	0.082

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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
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
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:00004226	Breast	Precancer	autophagy of mitochondrion	14/1080	81/18723	2.01e-04	3.16e-03	14
GO:00617266	Breast	Precancer	mitochondrion disassembly	14/1080	81/18723	2.01e-04	3.16e-03	14
GO:00316679	Breast	Precancer	response to nutrient levels	47/1080	474/18723	2.09e-04	3.27e-03	47
GO:00224119	Breast	Precancer	cellular component disassembly	44/1080	443/18723	3.17e-04	4.51e-03	44
GO:00714969	Breast	Precancer	cellular response to external stimulus	33/1080	320/18723	9.01e-04	1.03e-02	33
GO:00316688	Breast	Precancer	cellular response to extracellular stimulus	27/1080	246/18723	1.02e-03	1.13e-02	27
GO:00092677	Breast	Precancer	cellular response to starvation	19/1080	156/18723	1.65e-03	1.67e-02	19
GO:00425947	Breast	Precancer	response to starvation	22/1080	197/18723	2.30e-03	2.15e-02	22
GO:19030085	Breast	Precancer	organelle disassembly	15/1080	114/18723	2.31e-03	2.15e-02	15
GO:00316697	Breast	Precancer	cellular response to nutrient levels	22/1080	215/18723	6.58e-03	4.53e-02	22
GO:003166714	Breast	IDC	response to nutrient levels	62/1434	474/18723	2.33e-05	5.57e-04	62
GO:007149614	Breast	IDC	cellular response to external stimulus	45/1434	320/18723	5.40e-05	1.15e-03	45
GO:003166814	Breast	IDC	cellular response to extracellular stimulus	35/1434	246/18723	2.79e-04	4.26e-03	35
GO:000042212	Breast	IDC	autophagy of mitochondrion	15/1434	81/18723	1.13e-03	1.23e-02	15
GO:006172612	Breast	IDC	mitochondrion disassembly	15/1434	81/18723	1.13e-03	1.23e-02	15
GO:003166914	Breast	IDC	cellular response to nutrient levels	28/1434	215/18723	4.02e-03	3.25e-02	28
GO:190300812	Breast	IDC	organelle disassembly	17/1434	114/18723	5.99e-03	4.31e-02	17
GO:007149623	Breast	DCIS	cellular response to external stimulus	45/1390	320/18723	2.55e-05	5.87e-04	45
GO:003166723	Breast	DCIS	response to nutrient levels	58/1390	474/18723	1.16e-04	2.03e-03	58
GO:003166822	Breast	DCIS	cellular response to extracellular stimulus	35/1390	246/18723	1.54e-04	2.59e-03	35

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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

WDR45B

SNV

Missense_Mutation

c.923T>G

p.Val308Gly

p.V308G

Q5MNZ6

protein_coding

deleterious(0)

possibly_damaging(0.832)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

WDR45B

SNV

Missense_Mutation

novel

c.734T>A

p.Ile245Asn

p.I245N

Q5MNZ6

protein_coding

deleterious(0)

benign(0.24)

TCGA-BH-A0BM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

WDR45B

insertion

Nonsense_Mutation

novel

c.777_778insTCTTAACCCTGTAGCCAACACCGGGTGATTAGATGCTCACCCCAAGACCGTCA

p.Glu260SerfsTer2

p.E260Sfs*2

Q5MNZ6

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

WDR45B

insertion

Frame_Shift_Ins

novel

c.731_732insACTACAAATTCCTGTT

p.Ile245LeufsTer21

p.I245Lfs*21

Q5MNZ6

protein_coding

TCGA-BH-A0BM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

WDR45B

SNV

Missense_Mutation

novel

c.866N>G

p.Phe289Cys

p.F289C

Q5MNZ6

protein_coding

deleterious(0)

possibly_damaging(0.818)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WDR45B

SNV

Missense_Mutation

novel

c.322N>T

p.Arg108Trp

p.R108W

Q5MNZ6

protein_coding

deleterious(0)

probably_damaging(0.958)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WDR45B

SNV

Missense_Mutation

c.77N>T

p.Ala26Val

p.A26V

Q5MNZ6

protein_coding

deleterious(0.04)

benign(0.092)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WDR45B

SNV

Missense_Mutation

rs780142007

c.1024G>A

p.Asp342Asn

p.D342N

Q5MNZ6

protein_coding

deleterious(0.04)

benign(0.017)

TCGA-C5-A2LX-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WDR45B

SNV

Missense_Mutation

c.249N>A

p.Met83Ile

p.M83I

Q5MNZ6

protein_coding

tolerated(0.23)

benign(0)

TCGA-EA-A3HR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

WDR45B

SNV

Missense_Mutation

novel

c.887N>T

p.Pro296Leu

p.P296L

Q5MNZ6

protein_coding

tolerated(0.05)

benign(0.084)

TCGA-VS-A9UD-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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