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: ZMYND8

Gene summary for ZMYND8

Gene summary.

Gene information	Species	Human
	Gene symbol	ZMYND8
	Gene ID	23613
	Gene name	zinc finger MYND-type containing 8
	Gene Alias	PRKCBP1
	Cytomap	20q13.12
	Gene Type	protein-coding
	GO ID	GO:0001941
	UniProtAcc	Q569J9

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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
23613	ZMYND8	GSM4909286	Human	Breast	IDC	3.12e-07	1.52e-01	0.1081
23613	ZMYND8	GSM4909292	Human	Breast	IDC	7.71e-05	7.31e-01	0.1236
23613	ZMYND8	GSM4909293	Human	Breast	IDC	4.29e-04	1.67e-01	0.1581
23613	ZMYND8	GSM4909298	Human	Breast	IDC	3.34e-02	1.67e-01	0.1551
23613	ZMYND8	GSM4909301	Human	Breast	IDC	1.57e-51	9.69e-01	0.1577
23613	ZMYND8	GSM4909304	Human	Breast	IDC	3.03e-04	3.09e-01	0.1636
23613	ZMYND8	GSM4909311	Human	Breast	IDC	8.46e-04	-5.37e-02	0.1534
23613	ZMYND8	GSM4909319	Human	Breast	IDC	2.29e-08	-1.02e-01	0.1563
23613	ZMYND8	GSM4909321	Human	Breast	IDC	2.44e-02	3.29e-02	0.1559
23613	ZMYND8	M1	Human	Breast	IDC	6.40e-25	8.07e-01	0.1577
23613	ZMYND8	NCCBC5	Human	Breast	DCIS	8.01e-04	5.37e-02	0.2046
23613	ZMYND8	P1	Human	Breast	IDC	4.41e-12	3.36e-01	0.1527
23613	ZMYND8	DCIS2	Human	Breast	DCIS	1.42e-28	1.15e-01	0.0085
23613	ZMYND8	HTA11_2487_2000001011	Human	Colorectum	SER	2.01e-03	5.14e-01	-0.1808
23613	ZMYND8	HTA11_1938_2000001011	Human	Colorectum	AD	1.61e-10	8.12e-01	-0.0811
23613	ZMYND8	HTA11_78_2000001011	Human	Colorectum	AD	4.91e-02	4.94e-01	-0.1088
23613	ZMYND8	HTA11_347_2000001011	Human	Colorectum	AD	8.03e-16	7.16e-01	-0.1954
23613	ZMYND8	HTA11_411_2000001011	Human	Colorectum	SER	9.88e-08	1.12e+00	-0.2602
23613	ZMYND8	HTA11_2112_2000001011	Human	Colorectum	SER	2.00e-02	6.93e-01	-0.2196
23613	ZMYND8	HTA11_696_2000001011	Human	Colorectum	AD	8.02e-10	6.82e-01	-0.1464

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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
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
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
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:20001464	Endometrium	AEH	negative regulation of cell motility	67/2100	359/18723	1.86e-05	3.77e-04	67
GO:00512714	Endometrium	AEH	negative regulation of cellular component movement	68/2100	367/18723	2.06e-05	4.11e-04	68
GO:00400134	Endometrium	AEH	negative regulation of locomotion	70/2100	391/18723	4.95e-05	8.05e-04	70
GO:00163588	Endometrium	AEH	dendrite development	46/2100	243/18723	2.56e-04	3.03e-03	46
GO:00313468	Endometrium	AEH	positive regulation of cell projection organization	61/2100	353/18723	3.91e-04	4.20e-03	61
GO:00439546	Endometrium	AEH	cellular component maintenance	16/2100	61/18723	8.71e-04	8.04e-03	16
GO:19054759	Endometrium	AEH	regulation of protein localization to membrane	34/2100	175/18723	9.62e-04	8.75e-03	34
GO:00508086	Endometrium	AEH	synapse organization	67/2100	426/18723	2.67e-03	1.94e-02	67
GO:01200329	Endometrium	AEH	regulation of plasma membrane bounded cell projection assembly	34/2100	186/18723	2.79e-03	2.01e-02	34
GO:00604918	Endometrium	AEH	regulation of cell projection assembly	34/2100	188/18723	3.33e-03	2.32e-02	34
GO:200014613	Endometrium	EEC	negative regulation of cell motility	71/2168	359/18723	3.98e-06	1.04e-04	71
GO:005127113	Endometrium	EEC	negative regulation of cellular component movement	72/2168	367/18723	4.59e-06	1.15e-04	72
GO:003033612	Endometrium	EEC	negative regulation of cell migration	67/2168	344/18723	1.24e-05	2.54e-04	67
GO:004001312	Endometrium	EEC	negative regulation of locomotion	74/2168	391/18723	1.28e-05	2.59e-04	74
GO:003134613	Endometrium	EEC	positive regulation of cell projection organization	61/2168	353/18723	8.82e-04	8.03e-03	61
GO:190547514	Endometrium	EEC	regulation of protein localization to membrane	34/2168	175/18723	1.66e-03	1.30e-02	34
GO:001635813	Endometrium	EEC	dendrite development	44/2168	243/18723	1.72e-03	1.34e-02	44
GO:012003214	Endometrium	EEC	regulation of plasma membrane bounded cell projection assembly	35/2168	186/18723	2.52e-03	1.84e-02	35
GO:006049114	Endometrium	EEC	regulation of cell projection assembly	35/2168	188/18723	3.02e-03	2.10e-02	35
GO:004395412	Endometrium	EEC	cellular component maintenance	15/2168	61/18723	3.41e-03	2.32e-02	15

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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

ZMYND8

SNV

Missense_Mutation

c.2435N>T

p.Pro812Leu

p.P812L

Q9ULU4

protein_coding

deleterious_low_confidence(0.02)

benign(0.046)

TCGA-A2-A0EV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

c.2783C>T

p.Ser928Leu

p.S928L

Q9ULU4

protein_coding

tolerated(0.11)

benign(0)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

c.1693C>T

p.Leu565Phe

p.L565F

Q9ULU4

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.975)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

novel

c.1625N>A

p.Arg542Gln

p.R542Q

Q9ULU4

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

novel

c.119N>T

p.Arg40Ile

p.R40I

Q9ULU4

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

rs767210378

c.2363N>T

p.Ala788Val

p.A788V

Q9ULU4

protein_coding

tolerated_low_confidence(0.08)

benign(0.087)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

novel

c.1949C>G

p.Ser650Cys

p.S650C

Q9ULU4

protein_coding

tolerated_low_confidence(0.09)

possibly_damaging(0.547)

TCGA-BH-A28O-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

ZMYND8

SNV

Missense_Mutation

rs143023321

c.1568N>T

p.Thr523Met

p.T523M

Q9ULU4

protein_coding

tolerated_low_confidence(0.28)

benign(0.005)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

c.2998N>A

p.Glu1000Lys

p.E1000K

Q9ULU4

protein_coding

tolerated(0.07)

probably_damaging(0.998)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

ZMYND8

SNV

Missense_Mutation

c.1542C>G

p.Phe514Leu

p.F514L

Q9ULU4

protein_coding

tolerated_low_confidence(0.2)

benign(0.061)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

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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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