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: HM13

Gene summary for HM13

Gene summary.

Gene information	Species	Human
	Gene symbol	HM13
	Gene ID	81502
	Gene name	histocompatibility minor 13
	Gene Alias	H13
	Cytomap	20q11.21
	Gene Type	protein-coding
	GO ID	GO:0001701
	UniProtAcc	A0A0S2Z5V7

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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
81502	HM13	CA_HPV_1	Human	Cervix	CC	6.82e-03	4.81e-03	0.0264
81502	HM13	N_HPV_1	Human	Cervix	N_HPV	6.05e-03	-1.26e-01	0.0079
81502	HM13	N_HPV_2	Human	Cervix	N_HPV	4.43e-02	1.23e-01	-0.0131
81502	HM13	Tumor	Human	Cervix	CC	1.24e-10	4.55e-01	0.1241
81502	HM13	sample3	Human	Cervix	CC	4.45e-27	5.27e-01	0.1387
81502	HM13	T3	Human	Cervix	CC	8.24e-19	5.31e-01	0.1389
81502	HM13	HTA11_2487_2000001011	Human	Colorectum	SER	2.22e-07	5.95e-01	-0.1808
81502	HM13	HTA11_1938_2000001011	Human	Colorectum	AD	3.75e-02	4.44e-01	-0.0811
81502	HM13	HTA11_347_2000001011	Human	Colorectum	AD	1.33e-10	4.14e-01	-0.1954
81502	HM13	HTA11_411_2000001011	Human	Colorectum	SER	2.10e-04	8.80e-01	-0.2602
81502	HM13	HTA11_2112_2000001011	Human	Colorectum	SER	3.78e-03	7.83e-01	-0.2196
81502	HM13	HTA11_83_2000001011	Human	Colorectum	SER	6.00e-03	4.74e-01	-0.1526
81502	HM13	HTA11_696_2000001011	Human	Colorectum	AD	5.74e-14	6.72e-01	-0.1464
81502	HM13	HTA11_866_2000001011	Human	Colorectum	AD	3.92e-03	3.53e-01	-0.1001
81502	HM13	HTA11_1391_2000001011	Human	Colorectum	AD	1.55e-19	9.76e-01	-0.059
81502	HM13	HTA11_866_3004761011	Human	Colorectum	AD	2.37e-11	5.45e-01	0.096
81502	HM13	HTA11_10711_2000001011	Human	Colorectum	AD	2.14e-06	4.80e-01	0.0338
81502	HM13	HTA11_7696_3000711011	Human	Colorectum	AD	2.29e-09	5.51e-01	0.0674
81502	HM13	HTA11_6818_2000001021	Human	Colorectum	AD	4.48e-03	3.96e-01	0.0588
81502	HM13	HTA11_99999970781_79442	Human	Colorectum	MSS	5.61e-04	3.57e-01	0.294

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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:003650314	Oral cavity	LP	ERAD pathway	57/4623	107/18723	1.99e-10	1.08e-08	57
GO:000170117	Oral cavity	LP	in utero embryonic development	142/4623	367/18723	1.48e-09	6.75e-08	142
GO:003252713	Oral cavity	LP	protein exit from endoplasmic reticulum	28/4623	48/18723	6.99e-07	1.86e-05	28
GO:003097013	Oral cavity	LP	retrograde protein transport, ER to cytosol	18/4623	29/18723	2.15e-05	3.51e-04	18
GO:190351313	Oral cavity	LP	endoplasmic reticulum to cytosol transport	18/4623	29/18723	2.15e-05	3.51e-04	18
GO:001648513	Oral cavity	LP	protein processing	83/4623	225/18723	2.87e-05	4.52e-04	83
GO:000646514	Oral cavity	LP	signal peptide processing	10/4623	14/18723	3.05e-04	3.12e-03	10
GO:003361913	Oral cavity	LP	membrane protein proteolysis	25/4623	57/18723	1.19e-03	9.62e-03	25
GO:001049825	Oral cavity	EOLP	proteasomal protein catabolic process	108/2218	490/18723	7.79e-11	9.51e-09	108
GO:003497624	Oral cavity	EOLP	response to endoplasmic reticulum stress	66/2218	256/18723	5.33e-10	4.31e-08	66
GO:003252721	Oral cavity	EOLP	protein exit from endoplasmic reticulum	20/2218	48/18723	1.68e-07	5.43e-06	20
GO:003097021	Oral cavity	EOLP	retrograde protein transport, ER to cytosol	13/2218	29/18723	9.41e-06	1.74e-04	13
GO:190351321	Oral cavity	EOLP	endoplasmic reticulum to cytosol transport	13/2218	29/18723	9.41e-06	1.74e-04	13
GO:000170123	Oral cavity	EOLP	in utero embryonic development	72/2218	367/18723	1.02e-05	1.83e-04	72
GO:003650321	Oral cavity	EOLP	ERAD pathway	25/2218	107/18723	6.07e-04	5.08e-03	25
GO:003361921	Oral cavity	EOLP	membrane protein proteolysis	16/2218	57/18723	7.07e-04	5.78e-03	16
GO:005160423	Oral cavity	EOLP	protein maturation	50/2218	294/18723	5.32e-03	2.77e-02	50
GO:001049831	Oral cavity	NEOLP	proteasomal protein catabolic process	103/2005	490/18723	1.08e-11	1.65e-09	103
GO:000170132	Oral cavity	NEOLP	in utero embryonic development	76/2005	367/18723	1.11e-08	5.44e-07	76
GO:003497632	Oral cavity	NEOLP	response to endoplasmic reticulum stress	56/2005	256/18723	1.39e-07	4.84e-06	56

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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

HM13

SNV

Missense_Mutation

novel

c.220N>A

p.Asp74Asn

p.D74N

Q8TCT9

protein_coding

deleterious(0)

possibly_damaging(0.661)

TCGA-AR-A2LR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HM13

SNV

Missense_Mutation

c.808N>A

p.Gly270Arg

p.G270R

Q8TCT9

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

HM13

insertion

Frame_Shift_Ins

novel

c.643_644insAGCTATCAAATTTGTACTCAGTGGCGCAAATATTATGTGTCCAGGT

p.Leu215GlnfsTer81

p.L215Qfs*81

Q8TCT9

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HM13

SNV

Missense_Mutation

novel

c.1075N>T

p.Leu359Phe

p.L359F

Q8TCT9

protein_coding

tolerated(0.07)

benign(0.435)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HM13

SNV

Missense_Mutation

c.1253C>T

p.Ser418Leu

p.S418L

Q8TCT9

protein_coding

deleterious_low_confidence(0.02)

benign(0)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

HM13

SNV

Missense_Mutation

c.776N>T

p.Ala259Val

p.A259V

Q8TCT9

protein_coding

deleterious(0)

benign(0.358)

TCGA-F4-6703-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

HM13

SNV

Missense_Mutation

novel

c.196N>C

p.Met66Leu

p.M66L

Q8TCT9

protein_coding

tolerated(0.2)

benign(0.01)

TCGA-AG-A032-01

Colorectum

rectum adenocarcinoma

Male

>=65

III/IV

Targeted Molecular therapy

bevacizumab

HM13

SNV

Missense_Mutation

novel

c.197N>A

p.Met66Lys

p.M66K

Q8TCT9

protein_coding

tolerated(0.65)

benign(0.003)

TCGA-AG-A032-01

Colorectum

rectum adenocarcinoma

Male

>=65

III/IV

Targeted Molecular therapy

bevacizumab

HM13

SNV

Missense_Mutation

novel

c.1244C>T

p.Ala415Val

p.A415V

Q8TCT9

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.682)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

HM13

SNV

Missense_Mutation

novel

c.706T>C

p.Phe236Leu

p.F236L

Q8TCT9

protein_coding

deleterious(0.05)

benign(0.051)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<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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