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: EHMT1

Gene summary for EHMT1

Gene summary.

Gene information	Species	Human
	Gene symbol	EHMT1
	Gene ID	79813
	Gene name	euchromatic histone lysine methyltransferase 1
	Gene Alias	EHMT1-IT1
	Cytomap	9q34.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q9H9B1

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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
79813	EHMT1	CCI_1	Human	Cervix	CC	5.45e-05	5.82e-01	0.528
79813	EHMT1	CCI_2	Human	Cervix	CC	5.70e-08	6.77e-01	0.5249
79813	EHMT1	CCI_3	Human	Cervix	CC	1.52e-19	1.05e+00	0.516
79813	EHMT1	CCII_1	Human	Cervix	CC	1.55e-02	3.27e-01	0.3249
79813	EHMT1	HTA11_3410_2000001011	Human	Colorectum	AD	1.11e-22	-6.93e-01	0.0155
79813	EHMT1	HTA11_2487_2000001011	Human	Colorectum	SER	3.81e-08	-4.92e-01	-0.1808
79813	EHMT1	HTA11_78_2000001011	Human	Colorectum	AD	1.31e-03	-4.28e-01	-0.1088
79813	EHMT1	HTA11_3361_2000001011	Human	Colorectum	AD	6.67e-07	-6.01e-01	-0.1207
79813	EHMT1	HTA11_5212_2000001011	Human	Colorectum	AD	6.34e-03	-6.48e-01	-0.2061
79813	EHMT1	HTA11_5216_2000001011	Human	Colorectum	SER	1.15e-03	-7.10e-01	-0.1462
79813	EHMT1	HTA11_7862_2000001011	Human	Colorectum	AD	1.74e-05	-5.86e-01	-0.0179
79813	EHMT1	HTA11_866_3004761011	Human	Colorectum	AD	2.37e-07	-4.63e-01	0.096
79813	EHMT1	HTA11_8622_2000001021	Human	Colorectum	SER	6.23e-04	-6.63e-01	0.0528
79813	EHMT1	HTA11_99999970781_79442	Human	Colorectum	MSS	4.23e-12	-4.53e-01	0.294
79813	EHMT1	HTA11_99999974143_84620	Human	Colorectum	MSS	6.42e-13	-4.92e-01	0.3005
79813	EHMT1	A001-C-207	Human	Colorectum	FAP	7.81e-05	-1.82e-01	0.1278
79813	EHMT1	A015-C-203	Human	Colorectum	FAP	5.01e-33	-2.10e-01	-0.1294
79813	EHMT1	A015-C-204	Human	Colorectum	FAP	1.24e-04	-1.87e-01	-0.0228
79813	EHMT1	A014-C-040	Human	Colorectum	FAP	1.56e-03	-9.55e-02	-0.1184
79813	EHMT1	A002-C-201	Human	Colorectum	FAP	3.46e-13	-1.03e-01	0.0324

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:00063257	Cervix	CC	chromatin organization	78/2311	409/18723	5.40e-05	8.02e-04	78
GO:00165705	Cervix	CC	histone modification	84/2311	463/18723	1.70e-04	2.01e-03	84
GO:00459955	Cervix	CC	regulation of embryonic development	19/2311	64/18723	1.78e-04	2.09e-03	19
GO:00096369	Cervix	CC	response to toxic substance	52/2311	262/18723	3.34e-04	3.52e-03	52
GO:00349685	Cervix	CC	histone lysine methylation	27/2311	115/18723	6.61e-04	6.09e-03	27
GO:00165715	Cervix	CC	histone methylation	30/2311	141/18723	1.88e-03	1.39e-02	30
GO:00180224	Cervix	CC	peptidyl-lysine methylation	28/2311	131/18723	2.43e-03	1.71e-02	28
GO:00064795	Cervix	CC	protein methylation	36/2311	181/18723	2.46e-03	1.71e-02	36
GO:00082135	Cervix	CC	protein alkylation	36/2311	181/18723	2.46e-03	1.71e-02	36
GO:00182054	Cervix	CC	peptidyl-lysine modification	62/2311	376/18723	1.04e-02	4.97e-02	62
GO:0009636	Colorectum	AD	response to toxic substance	88/3918	262/18723	1.12e-06	3.72e-05	88
GO:0006325	Colorectum	AD	chromatin organization	119/3918	409/18723	4.85e-05	8.33e-04	119
GO:0045995	Colorectum	AD	regulation of embryonic development	24/3918	64/18723	1.72e-03	1.43e-02	24
GO:0120162	Colorectum	AD	positive regulation of cold-induced thermogenesis	32/3918	97/18723	3.74e-03	2.63e-02	32
GO:0106106	Colorectum	AD	cold-induced thermogenesis	43/3918	144/18723	7.05e-03	4.31e-02	43
GO:0120161	Colorectum	AD	regulation of cold-induced thermogenesis	43/3918	144/18723	7.05e-03	4.31e-02	43
GO:1990845	Colorectum	AD	adaptive thermogenesis	46/3918	157/18723	7.97e-03	4.73e-02	46
GO:00096361	Colorectum	SER	response to toxic substance	71/2897	262/18723	8.63e-07	4.07e-05	71
GO:00063251	Colorectum	SER	chromatin organization	89/2897	409/18723	4.15e-04	6.17e-03	89
GO:0051567	Colorectum	SER	histone H3-K9 methylation	13/2897	37/18723	2.60e-03	2.40e-02	13

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00310	Colorectum	AD	Lysine degradation	27/2092	63/8465	1.17e-03	7.75e-03	4.94e-03	27
hsa04211	Colorectum	AD	Longevity regulating pathway	33/2092	89/8465	6.15e-03	2.68e-02	1.71e-02	33
hsa003101	Colorectum	AD	Lysine degradation	27/2092	63/8465	1.17e-03	7.75e-03	4.94e-03	27
hsa042111	Colorectum	AD	Longevity regulating pathway	33/2092	89/8465	6.15e-03	2.68e-02	1.71e-02	33
hsa042112	Colorectum	MSS	Longevity regulating pathway	33/1875	89/8465	9.33e-04	5.58e-03	3.42e-03	33
hsa003102	Colorectum	MSS	Lysine degradation	24/1875	63/8465	2.94e-03	1.39e-02	8.50e-03	24
hsa042113	Colorectum	MSS	Longevity regulating pathway	33/1875	89/8465	9.33e-04	5.58e-03	3.42e-03	33
hsa003103	Colorectum	MSS	Lysine degradation	24/1875	63/8465	2.94e-03	1.39e-02	8.50e-03	24
hsa003104	Colorectum	FAP	Lysine degradation	23/1404	63/8465	1.04e-04	9.46e-04	5.76e-04	23
hsa042114	Colorectum	FAP	Longevity regulating pathway	27/1404	89/8465	8.82e-04	5.20e-03	3.16e-03	27
hsa003105	Colorectum	FAP	Lysine degradation	23/1404	63/8465	1.04e-04	9.46e-04	5.76e-04	23
hsa042115	Colorectum	FAP	Longevity regulating pathway	27/1404	89/8465	8.82e-04	5.20e-03	3.16e-03	27
hsa003106	Colorectum	CRC	Lysine degradation	18/1091	63/8465	7.21e-04	6.34e-03	4.30e-03	18
hsa042116	Colorectum	CRC	Longevity regulating pathway	20/1091	89/8465	8.36e-03	3.93e-02	2.66e-02	20
hsa003107	Colorectum	CRC	Lysine degradation	18/1091	63/8465	7.21e-04	6.34e-03	4.30e-03	18
hsa042117	Colorectum	CRC	Longevity regulating pathway	20/1091	89/8465	8.36e-03	3.93e-02	2.66e-02	20
hsa0421114	Esophagus	ESCC	Longevity regulating pathway	58/4205	89/8465	2.19e-03	6.16e-03	3.16e-03	58
hsa0031010	Esophagus	ESCC	Lysine degradation	41/4205	63/8465	9.63e-03	2.27e-02	1.16e-02	41
hsa0421115	Esophagus	ESCC	Longevity regulating pathway	58/4205	89/8465	2.19e-03	6.16e-03	3.16e-03	58
hsa0031013	Esophagus	ESCC	Lysine degradation	41/4205	63/8465	9.63e-03	2.27e-02	1.16e-02	41

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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

EHMT1

SNV

Missense_Mutation

c.2330N>G

p.Leu777Arg

p.L777R

Q9H9B1

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A04U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EHMT1

SNV

Missense_Mutation

novel

c.3146N>T

p.Pro1049Leu

p.P1049L

Q9H9B1

protein_coding

deleterious(0.03)

possibly_damaging(0.868)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EHMT1

SNV

Missense_Mutation

novel

c.848C>T

p.Ala283Val

p.A283V

Q9H9B1

protein_coding

deleterious_low_confidence(0.05)

probably_damaging(0.99)

TCGA-A8-A09M-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

EHMT1

SNV

Missense_Mutation

c.3092G>T

p.Ser1031Ile

p.S1031I

Q9H9B1

protein_coding

deleterious(0.01)

possibly_damaging(0.799)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EHMT1

SNV

Missense_Mutation

novel

c.877N>G

p.Met293Val

p.M293V

Q9H9B1

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.867)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EHMT1

SNV

Missense_Mutation

novel

c.769C>A

p.His257Asn

p.H257N

Q9H9B1

protein_coding

deleterious_low_confidence(0.04)

possibly_damaging(0.476)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

EHMT1

SNV

Missense_Mutation

novel

c.3704G>C

p.Gly1235Ala

p.G1235A

Q9H9B1

protein_coding

deleterious(0)

possibly_damaging(0.889)

TCGA-AR-A5QQ-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

carboplatin

EHMT1

SNV

Missense_Mutation

rs761131393

c.838N>T

p.Val280Phe

p.V280F

Q9H9B1

protein_coding

tolerated_low_confidence(0.09)

possibly_damaging(0.564)

TCGA-BH-A0BM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EHMT1

SNV

Missense_Mutation

c.1037N>C

p.Met346Thr

p.M346T

Q9H9B1

protein_coding

tolerated_low_confidence(0.11)

benign(0.022)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EHMT1

SNV

Missense_Mutation

rs761131393

c.838G>T

p.Val280Phe

p.V280F

Q9H9B1

protein_coding

tolerated_low_confidence(0.09)

possibly_damaging(0.564)

TCGA-C8-A137-01

Breast

breast invasive carcinoma

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
79813	EHMT1	ENZYME, DRUGGABLE GENOME	inhibitor	249565918
79813	EHMT1	ENZYME, DRUGGABLE GENOME	inhibitor	178103593	CHEMBL569864
79813	EHMT1	ENZYME, DRUGGABLE GENOME	inhibitor	178103596
79813	EHMT1	ENZYME, DRUGGABLE GENOME	inhibitor	178103594

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