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:190547513	Breast	IDC	regulation of protein localization to membrane	28/1434	175/18723	1.56e-04	2.71e-03	28
GO:00512712	Breast	IDC	negative regulation of cellular component movement	48/1434	367/18723	1.88e-04	3.12e-03	48
GO:20001462	Breast	IDC	negative regulation of cell motility	46/1434	359/18723	4.01e-04	5.60e-03	46
GO:00303362	Breast	IDC	negative regulation of cell migration	43/1434	344/18723	1.01e-03	1.13e-02	43
GO:00400132	Breast	IDC	negative regulation of locomotion	47/1434	391/18723	1.39e-03	1.43e-02	47
GO:00423912	Breast	IDC	regulation of membrane potential	49/1434	434/18723	4.04e-03	3.25e-02	49
GO:005127111	Breast	DCIS	negative regulation of cellular component movement	48/1390	367/18723	8.97e-05	1.69e-03	48
GO:200014611	Breast	DCIS	negative regulation of cell motility	46/1390	359/18723	2.01e-04	3.23e-03	46
GO:190547522	Breast	DCIS	regulation of protein localization to membrane	26/1390	175/18723	5.31e-04	6.88e-03	26
GO:003033611	Breast	DCIS	negative regulation of cell migration	43/1390	344/18723	5.41e-04	6.96e-03	43
GO:004001311	Breast	DCIS	negative regulation of locomotion	47/1390	391/18723	7.30e-04	8.69e-03	47
GO:00423911	Breast	DCIS	regulation of membrane potential	47/1390	434/18723	5.87e-03	4.20e-02	47
GO:1905475	Colorectum	AD	regulation of protein localization to membrane	73/3918	175/18723	3.37e-10	2.93e-08	73
GO:0106027	Colorectum	AD	neuron projection organization	36/3918	93/18723	6.58e-05	1.07e-03	36
GO:0031346	Colorectum	AD	positive regulation of cell projection organization	104/3918	353/18723	8.26e-05	1.30e-03	104
GO:0043954	Colorectum	AD	cellular component maintenance	26/3918	61/18723	1.04e-04	1.56e-03	26
GO:0097061	Colorectum	AD	dendritic spine organization	31/3918	84/18723	5.48e-04	5.83e-03	31
GO:0099173	Colorectum	AD	postsynapse organization	51/3918	168/18723	2.47e-03	1.90e-02	51
GO:0016358	Colorectum	AD	dendrite development	69/3918	243/18723	3.32e-03	2.42e-02	69
GO:0050808	Colorectum	AD	synapse organization	112/3918	426/18723	4.25e-03	2.92e-02	112

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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

rs369116353

c.2411N>T

p.Thr804Met

p.T804M

Q9ULU4

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.591)

TCGA-CN-5361-01

Oral cavity

head & neck squamous cell carcinoma

Male

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

novel

c.275C>T

p.Pro92Leu

p.P92L

Q9ULU4

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.973)

TCGA-CN-A63W-01

Oral cavity

head & neck squamous cell carcinoma

Female

<65

I/II

Chemotherapy

vectibix

ZMYND8

SNV

Missense_Mutation

c.2783N>T

p.Ser928Leu

p.S928L

Q9ULU4

protein_coding

tolerated(0.11)

benign(0)

TCGA-CR-7388-01

Oral cavity

head & neck squamous cell carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

ZMYND8

SNV

Missense_Mutation

novel

c.3656C>T

p.Thr1219Met

p.T1219M

Q9ULU4

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.73)

TCGA-CV-7236-01

Oral cavity

head & neck squamous cell carcinoma

Female

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

novel

c.2941N>A

p.Arg981Ser

p.R981S

Q9ULU4

protein_coding

deleterious(0.04)

probably_damaging(0.999)

TCGA-CV-7421-01

Oral cavity

head & neck squamous cell carcinoma

Male

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

c.1811T>C

p.Val604Ala

p.V604A

Q9ULU4

protein_coding

deleterious_low_confidence(0.02)

benign(0.283)

TCGA-BR-4362-01

Stomach

stomach adenocarcinoma

Female

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

c.3029N>T

p.Ala1010Val

p.A1010V

Q9ULU4

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-BR-4370-01

Stomach

stomach adenocarcinoma

Female

>=65

I/II

Unknown

ZMYND8

SNV

Missense_Mutation

rs373435522

c.2702N>T

p.Thr901Met

p.T901M

Q9ULU4

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.947)

TCGA-BR-8372-01

Stomach

stomach adenocarcinoma

Male

<65

III/IV

Chemotherapy

etoposide

ZMYND8

SNV

Missense_Mutation

c.853A>C

p.Lys285Gln

p.K285Q

Q9ULU4

protein_coding

deleterious(0.01)

probably_damaging(0.987)

TCGA-BR-8680-01

Stomach

stomach adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

ZMYND8

SNV

Missense_Mutation

rs150888885

c.1424N>T

p.Thr475Met

p.T475M

Q9ULU4

protein_coding

deleterious_low_confidence(0.05)

benign(0.408)

TCGA-D7-A6EV-01

Stomach

stomach 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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