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:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:003497610	Cervix	CC	response to endoplasmic reticulum stress	57/2311	256/18723	5.81e-06	1.42e-04	57
GO:00017018	Cervix	CC	in utero embryonic development	71/2311	367/18723	7.21e-05	1.00e-03	71
GO:00064657	Cervix	CC	signal peptide processing	8/2311	14/18723	8.01e-05	1.09e-03	8
GO:00516048	Cervix	CC	protein maturation	56/2311	294/18723	5.90e-04	5.59e-03	56
GO:003497623	Cervix	N_HPV	response to endoplasmic reticulum stress	20/534	256/18723	4.88e-05	1.13e-03	20
GO:005160414	Cervix	N_HPV	protein maturation	20/534	294/18723	3.17e-04	4.75e-03	20
GO:001049815	Cervix	N_HPV	proteasomal protein catabolic process	27/534	490/18723	9.06e-04	1.08e-02	27
GO:00164854	Cervix	N_HPV	protein processing	15/534	225/18723	2.09e-03	2.00e-02	15
GO:000646511	Cervix	N_HPV	signal peptide processing	3/534	14/18723	6.64e-03	4.45e-02	3
GO:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0034976	Colorectum	AD	response to endoplasmic reticulum stress	90/3918	256/18723	8.48e-08	4.28e-06	90
GO:0001701	Colorectum	AD	in utero embryonic development	110/3918	367/18723	2.36e-05	4.62e-04	110
GO:0006465	Colorectum	AD	signal peptide processing	10/3918	14/18723	6.90e-05	1.11e-03	10
GO:0051604	Colorectum	AD	protein maturation	85/3918	294/18723	6.73e-04	6.91e-03	85
GO:0033619	Colorectum	AD	membrane protein proteolysis	21/3918	57/18723	4.16e-03	2.88e-02	21
GO:0036503	Colorectum	AD	ERAD pathway	34/3918	107/18723	5.57e-03	3.63e-02	34
GO:0016485	Colorectum	AD	protein processing	63/3918	225/18723	6.77e-03	4.19e-02	63
GO:00104981	Colorectum	SER	proteasomal protein catabolic process	132/2897	490/18723	3.08e-11	5.55e-09	132
GO:00349761	Colorectum	SER	response to endoplasmic reticulum stress	74/2897	256/18723	3.01e-08	2.05e-06	74

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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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