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: HLA-B

Gene summary for HLA-B

Gene summary.

Gene information	Species	Human
	Gene symbol	HLA-B
	Gene ID	3106
	Gene name	major histocompatibility complex, class I, B
	Gene Alias	AS
	Cytomap	6p21.33
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	E5FQ95

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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
3106	HLA-B	GSM4909281	Human	Breast	IDC	4.46e-26	5.25e-01	0.21
3106	HLA-B	GSM4909282	Human	Breast	IDC	6.20e-17	3.79e-01	-0.0288
3106	HLA-B	GSM4909285	Human	Breast	IDC	3.62e-15	-5.96e-01	0.21
3106	HLA-B	GSM4909286	Human	Breast	IDC	4.66e-85	-1.38e+00	0.1081
3106	HLA-B	GSM4909287	Human	Breast	IDC	1.46e-02	2.44e-01	0.2057
3106	HLA-B	GSM4909288	Human	Breast	IDC	4.47e-02	2.60e-01	0.0988
3106	HLA-B	GSM4909291	Human	Breast	IDC	1.14e-14	-7.13e-01	0.1753
3106	HLA-B	GSM4909294	Human	Breast	IDC	6.18e-22	-7.71e-01	0.2022
3106	HLA-B	GSM4909296	Human	Breast	IDC	6.18e-14	-5.07e-01	0.1524
3106	HLA-B	GSM4909297	Human	Breast	IDC	2.61e-03	-1.08e-01	0.1517
3106	HLA-B	GSM4909298	Human	Breast	IDC	1.08e-12	-5.58e-01	0.1551
3106	HLA-B	GSM4909299	Human	Breast	IDC	4.49e-04	2.38e-01	0.035
3106	HLA-B	GSM4909301	Human	Breast	IDC	2.82e-11	-5.57e-01	0.1577
3106	HLA-B	GSM4909302	Human	Breast	IDC	9.51e-04	-3.04e-01	0.1545
3106	HLA-B	GSM4909304	Human	Breast	IDC	8.58e-26	-6.90e-01	0.1636
3106	HLA-B	GSM4909305	Human	Breast	IDC	2.96e-03	3.20e-01	0.0436
3106	HLA-B	GSM4909307	Human	Breast	IDC	1.96e-07	2.95e-01	0.1569
3106	HLA-B	GSM4909308	Human	Breast	IDC	2.43e-25	5.26e-01	0.158
3106	HLA-B	GSM4909311	Human	Breast	IDC	5.01e-23	-2.58e-01	0.1534
3106	HLA-B	GSM4909312	Human	Breast	IDC	1.14e-17	-6.03e-01	0.1552

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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
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:00024839	Breast	Precancer	antigen processing and presentation of endogenous peptide antigen	8/1080	19/18723	5.10e-06	1.53e-04	8
GO:00198839	Breast	Precancer	antigen processing and presentation of endogenous antigen	9/1080	26/18723	8.75e-06	2.34e-04	9
GO:19037069	Breast	Precancer	regulation of hemopoiesis	41/1080	367/18723	3.95e-05	8.52e-04	41
GO:00027117	Breast	Precancer	positive regulation of T cell mediated immunity	12/1080	56/18723	6.72e-05	1.35e-03	12
GO:19021055	Breast	Precancer	regulation of leukocyte differentiation	32/1080	279/18723	1.66e-04	2.74e-03	32
GO:00019168	Breast	Precancer	positive regulation of T cell mediated cytotoxicity	8/1080	29/18723	1.73e-04	2.83e-03	8
GO:00480029	Breast	Precancer	antigen processing and presentation of peptide antigen	12/1080	62/18723	1.89e-04	3.04e-03	12
GO:00198859	Breast	Precancer	antigen processing and presentation of endogenous peptide antigen via MHC class I	6/1080	17/18723	2.59e-04	3.83e-03	6
GO:19031313	Breast	Precancer	mononuclear cell differentiation	43/1080	426/18723	2.61e-04	3.84e-03	43
GO:00024749	Breast	Precancer	antigen processing and presentation of peptide antigen via MHC class I	7/1080	28/18723	8.46e-04	9.82e-03	7
GO:00027094	Breast	Precancer	regulation of T cell mediated immunity	13/1080	85/18723	1.12e-03	1.23e-02	13
GO:00026836	Breast	Precancer	negative regulation of immune system process	41/1080	434/18723	1.33e-03	1.40e-02	41
GO:00019146	Breast	Precancer	regulation of T cell mediated cytotoxicity	8/1080	39/18723	1.48e-03	1.53e-02	8
GO:00019134	Breast	Precancer	T cell mediated cytotoxicity	9/1080	49/18723	1.74e-03	1.74e-02	9
GO:00024563	Breast	Precancer	T cell mediated immunity	14/1080	109/18723	3.97e-03	3.15e-02	14
GO:0002821	Breast	Precancer	positive regulation of adaptive immune response	14/1080	112/18723	5.08e-03	3.82e-02	14
GO:004800213	Breast	IDC	antigen processing and presentation of peptide antigen	18/1434	62/18723	5.28e-07	2.59e-05	18
GO:000248314	Breast	IDC	antigen processing and presentation of endogenous peptide antigen	9/1434	19/18723	4.03e-06	1.43e-04	9
GO:001988313	Breast	IDC	antigen processing and presentation of endogenous antigen	10/1434	26/18723	1.14e-05	3.08e-04	10
GO:190370612	Breast	IDC	regulation of hemopoiesis	49/1434	367/18723	9.74e-05	1.86e-03	49

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516718	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0461218	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0516918	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa042189	Breast	Precancer	Cellular senescence	29/684	156/8465	1.66e-05	1.69e-04	1.30e-04	29
hsa0414518	Breast	Precancer	Phagosome	27/684	152/8465	7.37e-05	6.85e-04	5.25e-04	27
hsa0541618	Breast	Precancer	Viral myocarditis	14/684	60/8465	2.32e-04	1.98e-03	1.52e-03	14
hsa0516618	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0516316	Breast	Precancer	Human cytomegalovirus infection	32/684	225/8465	1.13e-03	7.57e-03	5.80e-03	32
hsa052036	Breast	Precancer	Viral carcinogenesis	27/684	204/8465	7.19e-03	4.06e-02	3.11e-02	27
hsa0516719	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0461219	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0516919	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa0421814	Breast	Precancer	Cellular senescence	29/684	156/8465	1.66e-05	1.69e-04	1.30e-04	29
hsa0414519	Breast	Precancer	Phagosome	27/684	152/8465	7.37e-05	6.85e-04	5.25e-04	27
hsa0541619	Breast	Precancer	Viral myocarditis	14/684	60/8465	2.32e-04	1.98e-03	1.52e-03	14
hsa0516619	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0516317	Breast	Precancer	Human cytomegalovirus infection	32/684	225/8465	1.13e-03	7.57e-03	5.80e-03	32
hsa0520312	Breast	Precancer	Viral carcinogenesis	27/684	204/8465	7.19e-03	4.06e-02	3.11e-02	27
hsa0516922	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0461223	Breast	IDC	Antigen processing and presentation	24/867	78/8465	4.61e-07	8.33e-06	6.23e-06	24

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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
HLA-B	CD8A	HLA-B_CD8A	MHC-I	Breast	ADJ
HLA-B	CD8B	HLA-B_CD8B	MHC-I	Breast	ADJ
HLA-B	CD8A	HLA-B_CD8A	MHC-I	Breast	DCIS
HLA-B	CD8B	HLA-B_CD8B	MHC-I	Breast	DCIS
HLA-B	CD8A	HLA-B_CD8A	MHC-I	Breast	Healthy
HLA-B	CD8B	HLA-B_CD8B	MHC-I	Breast	Healthy
HLA-B	CD8A	HLA-B_CD8A	MHC-I	Breast	IDC
HLA-B	CD8B	HLA-B_CD8B	MHC-I	Breast	IDC
HLA-B	CD8A	HLA-B_CD8A	MHC-I	Breast	Precancer
HLA-B	CD8B	HLA-B_CD8B	MHC-I	Breast	Precancer
HLA-B	CD8A	HLA-B_CD8A	MHC-I	Cervix	ADJ
HLA-B	CD8B	HLA-B_CD8B	MHC-I	Cervix	ADJ
HLA-B	CD8A	HLA-B_CD8A	MHC-I	Cervix	CC
HLA-B	CD8B	HLA-B_CD8B	MHC-I	Cervix	CC
HLA-B	CD8A	HLA-B_CD8A	MHC-I	Cervix	Healthy
HLA-B	CD8B	HLA-B_CD8B	MHC-I	Cervix	Healthy
HLA-B	CD8A	HLA-B_CD8A	MHC-I	Cervix	Precancer
HLA-B	CD8B	HLA-B_CD8B	MHC-I	Cervix	Precancer
HLA-B	CD8A	HLA-B_CD8A	MHC-I	CRC	AD
HLA-B	CD8B	HLA-B_CD8B	MHC-I	CRC	AD

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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

HLA-B

SNV

Missense_Mutation

c.911C>G

p.Ser304Cys

p.S304C

P01889,P30480,P30486,Q29836,Q31612,Q31610

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.806)

TCGA-AN-A0FL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HLA-B

SNV

Missense_Mutation

c.337G>C

p.Glu113Gln

p.E113Q

P01889,P30480,P30486,Q29836,Q31612,Q31610

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.998)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

HLA-B

SNV

Missense_Mutation

rs137854727

c.427N>T

p.Asp143Tyr

p.D143Y

P01889,P30480,P30486,Q29836,Q31612,Q31610

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-C5-A7UI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HLA-B

SNV

Missense_Mutation

c.1016G>T

p.Gly339Val

p.G339V

P01889,P30480,P30486,Q29836,Q31612,Q31610

protein_coding

tolerated_low_confidence(0.15)

probably_damaging(0.952)

TCGA-C5-A7X8-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HLA-B

SNV

Missense_Mutation

rs151341328

c.595N>A

p.Gly199Arg

p.G199R

P01889,P30480,P30486,Q29836,Q31612,Q31610

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(1)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HLA-B

insertion

Frame_Shift_Ins

novel

c.57_58insTG

p.Thr20Ter

p.T20*

P01889,P30480,P30486,Q29836,Q31612,Q31610

protein_coding

TCGA-JW-A5VI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

topotecan

HLA-B

insertion

Frame_Shift_Ins

novel

c.244_245insG

p.Glu82GlyfsTer17

p.E82Gfs*17

P01889,P30480,P30486,Q29836,Q31612,Q31610

protein_coding

TCGA-VS-A9UY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HLA-B

insertion

Frame_Shift_Ins

novel

c.696dupC

p.Tyr233LeufsTer21

p.Y233Lfs*21

P01889,P30480,P30486,Q29836,Q31612,Q31610

protein_coding

TCGA-ZX-AA5X-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

HLA-B

SNV

Missense_Mutation

novel

c.630N>T

p.Lys210Asn

p.K210N

P01889,P30480,P30486,Q29836,Q31612,Q31610

protein_coding

deleterious_low_confidence(0.03)

possibly_damaging(0.615)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

HLA-B

SNV

Missense_Mutation

novel

c.148N>T

p.Gly50Cys

p.G50C

P01889,P30480,P30486,Q29836,Q31612,Q31610

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-CK-5916-01

Colorectum

colon 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
3106	HLA-B	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		Pazopanib	PAZOPANIB
3106	HLA-B	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		interferons		23360626
3106	HLA-B	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		Antithyroid Preparations		27157822
3106	HLA-B	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		minocycline	MINOCYCLINE
3106	HLA-B	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		dapsone	DAPSONE	28885988,23604100,24152261,29512326,29458119
3106	HLA-B	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		BCG	BCG VACCINE	17028812
3106	HLA-B	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		ticlopidine	TICLOPIDINE	17339877
3106	HLA-B	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		clozapine	CLOZAPINE	9587740,26876947,2222133
3106	HLA-B	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		IFN		7507709,8081556
3106	HLA-B	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		Carbamazepine	CARBAMAZEPINE

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