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: HMCES

Gene summary for HMCES

Gene summary.

Gene information	Species	Human
	Gene symbol	HMCES
	Gene ID	56941
	Gene name	5-hydroxymethylcytosine binding, ES cell specific
	Gene Alias	C3orf37
	Cytomap	3q21.3
	Gene Type	protein-coding
	GO ID	GO:0000018
	UniProtAcc	Q96FZ2

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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
56941	HMCES	HTA11_2487_2000001011	Human	Colorectum	SER	3.84e-04	2.28e-01	-0.1808
56941	HMCES	HTA11_347_2000001011	Human	Colorectum	AD	6.73e-07	3.10e-01	-0.1954
56941	HMCES	HTA11_83_2000001011	Human	Colorectum	SER	5.49e-05	2.83e-01	-0.1526
56941	HMCES	HTA11_866_2000001011	Human	Colorectum	AD	3.27e-02	2.14e-01	-0.1001
56941	HMCES	HTA11_866_3004761011	Human	Colorectum	AD	1.09e-05	3.17e-01	0.096
56941	HMCES	HTA11_7696_3000711011	Human	Colorectum	AD	1.44e-04	2.52e-01	0.0674
56941	HMCES	HTA11_99999971662_82457	Human	Colorectum	MSS	3.78e-08	3.85e-01	0.3859
56941	HMCES	A015-C-203	Human	Colorectum	FAP	1.71e-02	-1.02e-01	-0.1294
56941	HMCES	A015-C-104	Human	Colorectum	FAP	1.71e-02	-1.12e-01	-0.1899
56941	HMCES	LZE2T	Human	Esophagus	ESCC	4.33e-02	7.86e-01	0.082
56941	HMCES	LZE4T	Human	Esophagus	ESCC	1.93e-09	5.71e-01	0.0811
56941	HMCES	LZE7T	Human	Esophagus	ESCC	2.04e-14	1.20e+00	0.0667
56941	HMCES	LZE8T	Human	Esophagus	ESCC	1.53e-08	2.92e-01	0.067
56941	HMCES	LZE22T	Human	Esophagus	ESCC	9.45e-06	3.11e-01	0.068
56941	HMCES	LZE24T	Human	Esophagus	ESCC	9.33e-15	4.60e-01	0.0596
56941	HMCES	LZE6T	Human	Esophagus	ESCC	1.46e-08	2.59e-01	0.0845
56941	HMCES	P1T-E	Human	Esophagus	ESCC	2.92e-10	5.97e-01	0.0875
56941	HMCES	P2T-E	Human	Esophagus	ESCC	2.68e-62	1.13e+00	0.1177
56941	HMCES	P4T-E	Human	Esophagus	ESCC	3.66e-38	1.22e+00	0.1323
56941	HMCES	P5T-E	Human	Esophagus	ESCC	1.09e-48	9.43e-01	0.1327

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:0051052	Colorectum	AD	regulation of DNA metabolic process	116/3918	359/18723	2.47e-07	1.00e-05	116
GO:0051054	Colorectum	AD	positive regulation of DNA metabolic process	73/3918	201/18723	3.27e-07	1.29e-05	73
GO:00510541	Colorectum	SER	positive regulation of DNA metabolic process	53/2897	201/18723	4.51e-05	1.13e-03	53
GO:00510521	Colorectum	SER	regulation of DNA metabolic process	83/2897	359/18723	8.03e-05	1.77e-03	83
GO:00510522	Colorectum	MSS	regulation of DNA metabolic process	108/3467	359/18723	5.86e-08	3.10e-06	108
GO:00510542	Colorectum	MSS	positive regulation of DNA metabolic process	69/3467	201/18723	6.33e-08	3.26e-06	69
GO:0006302	Colorectum	MSS	double-strand break repair	64/3467	251/18723	3.58e-03	2.65e-02	64
GO:00510524	Colorectum	FAP	regulation of DNA metabolic process	84/2622	359/18723	9.80e-07	4.38e-05	84
GO:00510544	Colorectum	FAP	positive regulation of DNA metabolic process	53/2622	201/18723	2.55e-06	9.82e-05	53
GO:005105215	Esophagus	ESCC	regulation of DNA metabolic process	232/8552	359/18723	2.40e-13	1.13e-11	232
GO:005105417	Esophagus	ESCC	positive regulation of DNA metabolic process	139/8552	201/18723	1.20e-11	4.33e-10	139
GO:00063024	Esophagus	ESCC	double-strand break repair	152/8552	251/18723	1.33e-06	1.62e-05	152
GO:00063101	Esophagus	ESCC	DNA recombination	168/8552	305/18723	5.58e-04	3.05e-03	168
GO:00025622	Esophagus	ESCC	somatic diversification of immune receptors via germline recombination within a single locus	43/8552	66/18723	1.10e-03	5.53e-03	43
GO:0006303	Esophagus	ESCC	double-strand break repair via nonhomologous end joining	43/8552	66/18723	1.10e-03	5.53e-03	43
GO:00164442	Esophagus	ESCC	somatic cell DNA recombination	43/8552	66/18723	1.10e-03	5.53e-03	43
GO:00164472	Esophagus	ESCC	somatic recombination of immunoglobulin gene segments	38/8552	57/18723	1.11e-03	5.56e-03	38
GO:00022003	Esophagus	ESCC	somatic diversification of immune receptors	49/8552	77/18723	1.12e-03	5.60e-03	49
GO:00164452	Esophagus	ESCC	somatic diversification of immunoglobulins	43/8552	67/18723	1.73e-03	7.97e-03	43
GO:00023815	Esophagus	ESCC	immunoglobulin production involved in immunoglobulin-mediated immune response	44/8552	70/18723	2.80e-03	1.19e-02	44

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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

HMCES

SNV

Missense_Mutation

c.91G>C

p.Glu31Gln

p.E31Q

Q96FZ2

protein_coding

tolerated(0.17)

benign(0.026)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HMCES

SNV

Missense_Mutation

c.298G>A

p.Asp100Asn

p.D100N

Q96FZ2

protein_coding

deleterious(0)

probably_damaging(0.961)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HMCES

SNV

Missense_Mutation

c.199N>C

p.Glu67Gln

p.E67Q

Q96FZ2

protein_coding

deleterious(0.01)

possibly_damaging(0.875)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

HMCES

deletion

Frame_Shift_Del

novel

c.158delN

p.Leu54CysfsTer49

p.L54Cfs*49

Q96FZ2

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

HMCES

SNV

Missense_Mutation

rs369963919

c.1048N>T

p.Arg350Cys

p.R350C

Q96FZ2

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.53)

TCGA-A6-3809-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

HMCES

SNV

Missense_Mutation

rs367763626

c.779N>A

p.Arg260Gln

p.R260Q

Q96FZ2

protein_coding

deleterious(0.01)

possibly_damaging(0.847)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

HMCES

insertion

Frame_Shift_Ins

novel

c.700_701insG

p.Thr234SerfsTer32

p.T234Sfs*32

Q96FZ2

protein_coding

TCGA-AY-4070-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

5-fu

HMCES

SNV

Missense_Mutation

novel

c.934N>T

p.Pro312Ser

p.P312S

Q96FZ2

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

HMCES

SNV

Missense_Mutation

novel

c.944C>A

p.Ser315Tyr

p.S315Y

Q96FZ2

protein_coding

deleterious(0)

possibly_damaging(0.862)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

HMCES

SNV

Missense_Mutation

c.574N>A

p.Leu192Met

p.L192M

Q96FZ2

protein_coding

deleterious(0.03)

probably_damaging(1)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid 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

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