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: ZNF451

Gene summary for ZNF451

Gene summary.

Gene information	Species	Human
	Gene symbol	ZNF451
	Gene ID	26036
	Gene name	zinc finger protein 451
	Gene Alias	COASTER
	Cytomap	6p12.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q96JY2

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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
26036	ZNF451	P128T-E	Human	Esophagus	ESCC	1.83e-19	6.85e-01	0.1241
26036	ZNF451	P130T-E	Human	Esophagus	ESCC	2.27e-64	1.09e+00	0.1676
26036	ZNF451	NAFLD1	Human	Liver	NAFLD	7.74e-04	5.39e-01	-0.04
26036	ZNF451	S43	Human	Liver	Cirrhotic	5.07e-03	-7.67e-02	-0.0187
26036	ZNF451	HCC1_Meng	Human	Liver	HCC	6.96e-44	3.77e-03	0.0246
26036	ZNF451	HCC2_Meng	Human	Liver	HCC	1.88e-22	8.52e-02	0.0107
26036	ZNF451	HCC1	Human	Liver	HCC	2.17e-09	4.62e+00	0.5336
26036	ZNF451	HCC2	Human	Liver	HCC	2.45e-05	3.19e+00	0.5341
26036	ZNF451	Pt13.b	Human	Liver	HCC	3.98e-10	1.71e-01	0.0251
26036	ZNF451	S014	Human	Liver	HCC	9.13e-05	4.81e-01	0.2254
26036	ZNF451	S015	Human	Liver	HCC	4.09e-06	5.15e-01	0.2375
26036	ZNF451	S016	Human	Liver	HCC	1.18e-07	5.14e-01	0.2243
26036	ZNF451	S027	Human	Liver	HCC	6.50e-03	5.14e-01	0.2446
26036	ZNF451	S028	Human	Liver	HCC	4.37e-11	5.98e-01	0.2503
26036	ZNF451	S029	Human	Liver	HCC	2.13e-02	4.79e-01	0.2581
26036	ZNF451	RNA-P17T-P17T-6	Human	Lung	IAC	1.72e-04	6.14e-01	0.3385
26036	ZNF451	RNA-P17T-P17T-8	Human	Lung	IAC	1.69e-06	6.84e-01	0.3329
26036	ZNF451	RNA-P25T1-P25T1-1	Human	Lung	AIS	1.57e-03	2.81e-01	-0.2116
26036	ZNF451	RNA-P25T1-P25T1-4	Human	Lung	AIS	5.09e-09	5.26e-01	-0.2119
26036	ZNF451	RNA-P6T2-P6T2-1	Human	Lung	IAC	1.44e-04	3.02e-01	-0.0166

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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
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
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:001657015	Esophagus	ESCC	histone modification	323/8552	463/18723	2.61e-26	7.88e-24	323
GO:001820514	Esophagus	ESCC	peptidyl-lysine modification	259/8552	376/18723	3.90e-20	5.26e-18	259
GO:001839413	Esophagus	ESCC	peptidyl-lysine acetylation	123/8552	169/18723	6.58e-13	2.94e-11	123
GO:004354313	Esophagus	ESCC	protein acylation	165/8552	243/18723	1.69e-12	7.14e-11	165
GO:000647313	Esophagus	ESCC	protein acetylation	140/8552	201/18723	4.37e-12	1.69e-10	140
GO:001839313	Esophagus	ESCC	internal peptidyl-lysine acetylation	114/8552	158/18723	1.16e-11	4.24e-10	114
GO:000647513	Esophagus	ESCC	internal protein amino acid acetylation	115/8552	160/18723	1.43e-11	5.08e-10	115
GO:00165735	Esophagus	ESCC	histone acetylation	110/8552	152/18723	1.95e-11	6.81e-10	110
GO:003105614	Esophagus	ESCC	regulation of histone modification	106/8552	152/18723	1.52e-09	3.55e-08	106
GO:00715599	Esophagus	ESCC	response to transforming growth factor beta	157/8552	256/18723	2.95e-07	4.23e-06	157
GO:00063673	Esophagus	ESCC	transcription initiation from RNA polymerase II promoter	56/8552	77/18723	1.30e-06	1.59e-05	56
GO:00715609	Esophagus	ESCC	cellular response to transforming growth factor beta stimulus	151/8552	250/18723	1.78e-06	2.10e-05	151
GO:000635211	Esophagus	ESCC	DNA-templated transcription, initiation	86/8552	130/18723	1.88e-06	2.19e-05	86
GO:001692512	Esophagus	ESCC	protein sumoylation	41/8552	53/18723	2.49e-06	2.86e-05	41
GO:00071799	Esophagus	ESCC	transforming growth factor beta receptor signaling pathway	121/8552	198/18723	8.26e-06	8.03e-05	121
GO:00439662	Esophagus	ESCC	histone H3 acetylation	43/8552	61/18723	7.57e-05	5.67e-04	43
GO:20007564	Esophagus	ESCC	regulation of peptidyl-lysine acetylation	43/8552	63/18723	2.43e-04	1.50e-03	43
GO:000717810	Esophagus	ESCC	transmembrane receptor protein serine/threonine kinase signaling pathway	195/8552	355/18723	2.58e-04	1.58e-03	195
GO:00602603	Esophagus	ESCC	regulation of transcription initiation from RNA polymerase II promoter	25/8552	33/18723	4.30e-04	2.43e-03	25
GO:200014212	Esophagus	ESCC	regulation of DNA-templated transcription, initiation	29/8552	40/18723	5.32e-04	2.93e-03	29

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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

ZNF451

SNV

Missense_Mutation

rs750718545

c.2891N>A

p.Arg964His

p.R964H

Q9Y4E5

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-B6-A1KI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZNF451

SNV

Missense_Mutation

novel

c.992N>T

p.Thr331Ile

p.T331I

Q9Y4E5

protein_coding

deleterious(0)

possibly_damaging(0.845)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ZNF451

SNV

Missense_Mutation

novel

c.1715N>T

p.Pro572Leu

p.P572L

Q9Y4E5

protein_coding

deleterious(0.02)

benign(0.322)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ZNF451

SNV

Missense_Mutation

c.2824N>C

p.Phe942Leu

p.F942L

Q9Y4E5

protein_coding

deleterious(0)

probably_damaging(0.971)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZNF451

SNV

Missense_Mutation

c.1215N>A

p.Ser405Arg

p.S405R

Q9Y4E5

protein_coding

tolerated(0.14)

benign(0.06)

TCGA-D8-A1JE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamicin

ZNF451

SNV

Missense_Mutation

c.877N>T

p.Pro293Ser

p.P293S

Q9Y4E5

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-E9-A1RH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

ZNF451

insertion

Frame_Shift_Ins

novel

c.1829_1830insAGGCAGAAGAGCC

p.Cys611GlyfsTer6

p.C611Gfs*6

Q9Y4E5

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZNF451

SNV

Missense_Mutation

novel

c.2642A>G

p.Tyr881Cys

p.Y881C

Q9Y4E5

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.635)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

ZNF451

SNV

Missense_Mutation

c.899N>T

p.Ala300Val

p.A300V

Q9Y4E5

protein_coding

tolerated(0.12)

probably_damaging(0.971)

TCGA-A6-6141-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

5-fu

ZNF451

SNV

Missense_Mutation

novel

c.1910N>C

p.Ser637Thr

p.S637T

Q9Y4E5

protein_coding

tolerated(0.31)

benign(0.084)

TCGA-AA-3845-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

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

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