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-A

Gene summary for HLA-A

Gene summary.

Gene information	Species	Human
	Gene symbol	HLA-A
	Gene ID	3105
	Gene name	major histocompatibility complex, class I, A
	Gene Alias	HLAA
	Cytomap	6p22.1
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	P30443

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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
3105	HLA-A	GSM4909281	Human	Breast	IDC	5.87e-22	6.00e-01	0.21
3105	HLA-A	GSM4909282	Human	Breast	IDC	8.98e-36	6.43e-01	-0.0288
3105	HLA-A	GSM4909285	Human	Breast	IDC	3.33e-18	-4.99e-01	0.21
3105	HLA-A	GSM4909286	Human	Breast	IDC	1.29e-43	-7.86e-01	0.1081
3105	HLA-A	GSM4909287	Human	Breast	IDC	1.69e-13	3.81e-01	0.2057
3105	HLA-A	GSM4909288	Human	Breast	IDC	1.91e-15	5.82e-01	0.0988
3105	HLA-A	GSM4909294	Human	Breast	IDC	2.09e-13	-3.22e-01	0.2022
3105	HLA-A	GSM4909296	Human	Breast	IDC	9.43e-12	-2.33e-01	0.1524
3105	HLA-A	GSM4909297	Human	Breast	IDC	2.91e-18	-5.67e-02	0.1517
3105	HLA-A	GSM4909298	Human	Breast	IDC	1.55e-03	-2.22e-01	0.1551
3105	HLA-A	GSM4909299	Human	Breast	IDC	3.17e-02	3.50e-01	0.035
3105	HLA-A	GSM4909301	Human	Breast	IDC	6.42e-08	-3.49e-01	0.1577
3105	HLA-A	GSM4909304	Human	Breast	IDC	1.10e-32	-7.24e-01	0.1636
3105	HLA-A	GSM4909305	Human	Breast	IDC	7.02e-13	4.96e-01	0.0436
3105	HLA-A	GSM4909307	Human	Breast	IDC	1.02e-06	3.78e-01	0.1569
3105	HLA-A	GSM4909308	Human	Breast	IDC	5.06e-21	5.33e-01	0.158
3105	HLA-A	GSM4909309	Human	Breast	IDC	3.39e-06	3.09e-01	0.0483
3105	HLA-A	GSM4909311	Human	Breast	IDC	1.17e-43	-4.36e-01	0.1534
3105	HLA-A	GSM4909312	Human	Breast	IDC	5.98e-31	-7.09e-01	0.1552
3105	HLA-A	GSM4909315	Human	Breast	IDC	4.58e-51	-9.02e-01	0.21

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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
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:0002832	Liver	Cirrhotic	negative regulation of response to biotic stimulus	41/4634	108/18723	1.56e-03	1.01e-02	41
GO:001988512	Liver	Cirrhotic	antigen processing and presentation of endogenous peptide antigen via MHC class I	10/4634	17/18723	2.85e-03	1.64e-02	10
GO:00458242	Liver	Cirrhotic	negative regulation of innate immune response	28/4634	71/18723	4.37e-03	2.31e-02	28
GO:00198837	Liver	Cirrhotic	antigen processing and presentation of endogenous antigen	13/4634	26/18723	4.72e-03	2.48e-02	13
GO:00028311	Liver	Cirrhotic	regulation of response to biotic stimulus	101/4634	327/18723	6.58e-03	3.25e-02	101
GO:001988212	Liver	HCC	antigen processing and presentation	65/7958	106/18723	7.06e-05	6.37e-04	65
GO:00028321	Liver	HCC	negative regulation of response to biotic stimulus	66/7958	108/18723	7.24e-05	6.50e-04	66
GO:00028312	Liver	HCC	regulation of response to biotic stimulus	173/7958	327/18723	8.55e-05	7.48e-04	173
GO:000248312	Liver	HCC	antigen processing and presentation of endogenous peptide antigen	16/7958	19/18723	2.37e-04	1.79e-03	16
GO:000247811	Liver	HCC	antigen processing and presentation of exogenous peptide antigen	27/7958	38/18723	3.47e-04	2.42e-03	27
GO:004800212	Liver	HCC	antigen processing and presentation of peptide antigen	40/7958	62/18723	3.84e-04	2.62e-03	40
GO:000247411	Liver	HCC	antigen processing and presentation of peptide antigen via MHC class I	21/7958	28/18723	4.94e-04	3.23e-03	21
GO:001988522	Liver	HCC	antigen processing and presentation of endogenous peptide antigen via MHC class I	14/7958	17/18723	9.39e-04	5.47e-03	14
GO:001988411	Liver	HCC	antigen processing and presentation of exogenous antigen	31/7958	47/18723	9.90e-04	5.71e-03	31
GO:004578512	Liver	HCC	positive regulation of cell adhesion	215/7958	437/18723	2.53e-03	1.22e-02	215
GO:00450881	Liver	HCC	regulation of innate immune response	113/7958	218/18723	3.27e-03	1.50e-02	113
GO:00458241	Liver	HCC	negative regulation of innate immune response	42/7958	71/18723	3.41e-03	1.55e-02	42
GO:0050777	Liver	HCC	negative regulation of immune response	101/7958	194/18723	4.40e-03	1.90e-02	101
GO:001988312	Liver	HCC	antigen processing and presentation of endogenous antigen	18/7958	26/18723	5.37e-03	2.24e-02	18
GO:000248322	Liver	Cyst	antigen processing and presentation of endogenous peptide antigen	7/496	19/18723	3.36e-07	3.68e-05	7

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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-A	CD8A	HLA-A_CD8A	MHC-I	Breast	ADJ
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Breast	ADJ
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Breast	DCIS
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Breast	DCIS
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Breast	Healthy
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Breast	Healthy
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Breast	IDC
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Breast	IDC
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Breast	Precancer
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Breast	Precancer
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Cervix	ADJ
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Cervix	ADJ
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Cervix	CC
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Cervix	CC
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Cervix	Healthy
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Cervix	Healthy
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Cervix	Precancer
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Cervix	Precancer
HLA-A	CD8A	HLA-A_CD8A	MHC-I	CRC	AD
HLA-A	CD8B	HLA-A_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-A

SNV

Missense_Mutation

c.640N>C

p.Thr214Pro

p.T214P

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.916)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HLA-A

SNV

Missense_Mutation

rs199474387

c.187N>C

p.Asp63His

p.D63H

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HLA-A

SNV

Missense_Mutation

rs199474481

c.360N>C

p.Gln120His

p.Q120H

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0)

benign(0.025)

TCGA-Q1-A73P-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HLA-A

SNV

Missense_Mutation

c.296N>C

p.Arg99Pro

p.R99P

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0.04)

probably_damaging(0.954)

TCGA-UC-A7PI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HLA-A

SNV

Missense_Mutation

novel

c.1016G>A

p.Arg339Lys

p.R339K

P04439,P13746,P16188

protein_coding

tolerated_low_confidence(0.95)

benign(0.019)

TCGA-VS-A9UD-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

HLA-A

insertion

Frame_Shift_Ins

novel

c.620_621insACCC

p.Asp207GlufsTer15

p.D207Efs*15

P04439,P13746,P16188

protein_coding

TCGA-EK-A2PK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HLA-A

insertion

Frame_Shift_Ins

novel

c.620_621insC

p.Lys210GlnfsTer11

p.K210Qfs*11

P04439,P13746,P16188

protein_coding

TCGA-EK-A2PL-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

HLA-A

SNV

Missense_Mutation

novel

c.776C>A

p.Pro259His

p.P259H

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

HLA-A

SNV

Missense_Mutation

c.373N>C

p.Cys125Arg

p.C125R

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

HLA-A

SNV

Missense_Mutation

rs758168864

c.547T>C

p.Tyr183His

p.Y183H

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.956)

TCGA-AA-A00N-01

Colorectum

colon 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
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		peginterferon alfa-2b		23360626
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		zonisamide	ZONISAMIDE	24236482
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		terbinafine	TERBINAFINE
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		peginterferon alfa-2a		23360626
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		ticlopidine	TICLOPIDINE	17339877
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		Carbamazepine	CARBAMAZEPINE
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		ribavirin	RIBAVIRIN	23360626
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		vancomycin	VANCOMYCIN	32439433
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		levetiracetam	LEVETIRACETAM	30020991
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		sertraline	SERTRALINE

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