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-DQA1

Gene summary for HLA-DQA1

Gene summary.

Gene information	Species	Human
	Gene symbol	HLA-DQA1
	Gene ID	3117
	Gene name	major histocompatibility complex, class II, DQ alpha 1
	Gene Alias	CELIAC1
	Cytomap	6p21.32
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	A0A173ADG5

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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
3117	HLA-DQA1	GSM4909287	Human	Breast	IDC	2.09e-18	6.57e-01	0.2057
3117	HLA-DQA1	GSM4909290	Human	Breast	IDC	4.48e-03	2.67e-01	0.2096
3117	HLA-DQA1	M1	Human	Breast	IDC	9.04e-07	3.24e-01	0.1577
3117	HLA-DQA1	M2	Human	Breast	IDC	2.40e-03	5.48e-01	0.21
3117	HLA-DQA1	NCCBC11	Human	Breast	DCIS	1.60e-08	9.27e-01	0.1232
3117	HLA-DQA1	NCCBC14	Human	Breast	DCIS	1.24e-02	3.26e-01	0.2021
3117	HLA-DQA1	NCCBC3	Human	Breast	DCIS	4.02e-35	8.56e-01	0.1198
3117	HLA-DQA1	NCCBC5	Human	Breast	DCIS	3.75e-21	8.79e-01	0.2046
3117	HLA-DQA1	P2	Human	Breast	IDC	1.76e-16	7.84e-01	0.21
3117	HLA-DQA1	CA_HPV_1	Human	Cervix	CC	1.27e-06	5.10e-01	0.0264
3117	HLA-DQA1	CA_HPV_3	Human	Cervix	CC	3.33e-07	-5.58e-01	0.0414
3117	HLA-DQA1	CCI_1	Human	Cervix	CC	1.14e-05	-7.67e-01	0.528
3117	HLA-DQA1	CCI_3	Human	Cervix	CC	3.63e-07	-7.46e-01	0.516
3117	HLA-DQA1	CCII_1	Human	Cervix	CC	3.52e-14	-7.97e-01	0.3249
3117	HLA-DQA1	Tumor	Human	Cervix	CC	1.36e-25	-7.85e-01	0.1241
3117	HLA-DQA1	sample1	Human	Cervix	CC	2.14e-13	8.40e-01	0.0959
3117	HLA-DQA1	sample3	Human	Cervix	CC	7.59e-28	-8.01e-01	0.1387
3117	HLA-DQA1	H2	Human	Cervix	HSIL_HPV	3.17e-16	-6.52e-01	0.0632
3117	HLA-DQA1	L1	Human	Cervix	CC	1.55e-06	-5.99e-01	0.0802
3117	HLA-DQA1	T1	Human	Cervix	CC	5.14e-18	7.36e-01	0.0918

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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
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
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:004800213	Breast	IDC	antigen processing and presentation of peptide antigen	18/1434	62/18723	5.28e-07	2.59e-05	18
GO:004578514	Breast	IDC	positive regulation of cell adhesion	62/1434	437/18723	1.70e-06	7.16e-05	62
GO:000250112	Breast	IDC	peptide antigen assembly with MHC protein complex	9/1434	18/18723	2.28e-06	9.05e-05	9
GO:000247813	Breast	IDC	antigen processing and presentation of exogenous peptide antigen	13/1434	38/18723	2.60e-06	1.01e-04	13
GO:000239612	Breast	IDC	MHC protein complex assembly	9/1434	19/18723	4.03e-06	1.43e-04	9
GO:00023997	Breast	IDC	MHC class II protein complex assembly	8/1434	16/18723	8.56e-06	2.47e-04	8
GO:00025037	Breast	IDC	peptide antigen assembly with MHC class II protein complex	8/1434	16/18723	8.56e-06	2.47e-04	8
GO:004211012	Breast	IDC	T cell activation	64/1434	487/18723	1.49e-05	3.77e-04	64
GO:005086311	Breast	IDC	regulation of T cell activation	47/1434	329/18723	2.49e-05	5.91e-04	47
GO:00024957	Breast	IDC	antigen processing and presentation of peptide antigen via MHC class II	11/1434	34/18723	2.81e-05	6.58e-04	11
GO:001988413	Breast	IDC	antigen processing and presentation of exogenous antigen	13/1434	47/18723	3.53e-05	8.08e-04	13
GO:005087011	Breast	IDC	positive regulation of T cell activation	34/1434	216/18723	4.59e-05	1.03e-03	34
GO:001988613	Breast	IDC	antigen processing and presentation of exogenous peptide antigen via MHC class II	10/1434	30/18723	4.87e-05	1.07e-03	10
GO:00025047	Breast	IDC	antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	11/1434	36/18723	5.13e-05	1.10e-03	11
GO:000715912	Breast	IDC	leukocyte cell-cell adhesion	49/1434	371/18723	1.27e-04	2.33e-03	49
GO:00198829	Breast	IDC	antigen processing and presentation	20/1434	106/18723	1.41e-04	2.49e-03	20
GO:190303911	Breast	IDC	positive regulation of leukocyte cell-cell adhesion	35/1434	239/18723	1.58e-04	2.73e-03	35
GO:190303711	Breast	IDC	regulation of leukocyte cell-cell adhesion	45/1434	336/18723	1.72e-04	2.92e-03	45
GO:002240712	Breast	IDC	regulation of cell-cell adhesion	55/1434	448/18723	3.43e-04	5.07e-03	55
GO:002240912	Breast	IDC	positive regulation of cell-cell adhesion	38/1434	284/18723	5.40e-04	6.96e-03	38

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516922	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0414522	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0516624	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0514012	Breast	IDC	Leishmaniasis	16/867	77/8465	4.35e-03	2.57e-02	1.92e-02	16
hsa0532010	Breast	IDC	Autoimmune thyroid disease	12/867	53/8465	6.29e-03	3.30e-02	2.47e-02	12
hsa0516932	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0414532	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0516634	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0514013	Breast	IDC	Leishmaniasis	16/867	77/8465	4.35e-03	2.57e-02	1.92e-02	16
hsa0532011	Breast	IDC	Autoimmune thyroid disease	12/867	53/8465	6.29e-03	3.30e-02	2.47e-02	12
hsa0516941	Breast	DCIS	Epstein-Barr virus infection	46/846	202/8465	5.60e-08	1.13e-06	8.33e-07	46
hsa0461242	Breast	DCIS	Antigen processing and presentation	25/846	78/8465	6.75e-08	1.28e-06	9.45e-07	25
hsa0414541	Breast	DCIS	Phagosome	35/846	152/8465	1.67e-06	2.45e-05	1.81e-05	35
hsa0541642	Breast	DCIS	Viral myocarditis	19/846	60/8465	3.12e-06	4.20e-05	3.09e-05	19
hsa0516642	Breast	DCIS	Human T-cell leukemia virus 1 infection	41/846	222/8465	7.03e-05	6.88e-04	5.07e-04	41
hsa0494021	Breast	DCIS	Type I diabetes mellitus	13/846	43/8465	1.91e-04	1.72e-03	1.27e-03	13
hsa0533021	Breast	DCIS	Allograft rejection	12/846	38/8465	2.13e-04	1.86e-03	1.37e-03	12
hsa0532341	Breast	DCIS	Rheumatoid arthritis	21/846	93/8465	2.64e-04	2.24e-03	1.65e-03	21
hsa0533221	Breast	DCIS	Graft-versus-host disease	12/846	42/8465	5.98e-04	4.49e-03	3.31e-03	12
hsa0514021	Breast	DCIS	Leishmaniasis	17/846	77/8465	1.29e-03	9.06e-03	6.67e-03	17

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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-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Breast	DCIS
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Breast	Healthy
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Breast	IDC
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Cervix	ADJ
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Cervix	CC
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Cervix	Healthy
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Cervix	Precancer
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	CRC	AD
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	CRC	ADJ
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	CRC	FAP
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	CRC	MSI-H
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	CRC	MSS
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	CRC	SER
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Endometrium	ADJ
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Endometrium	AEH
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Endometrium	EEC
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	Endometrium	Healthy
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	HNSCC	ADJ
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	HNSCC	Healthy
HLA-DQA1	CD4	HLA-DQA1_CD4	MHC-II	HNSCC	OSCC

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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-DQA1

SNV

Missense_Mutation

c.151G>C

p.Glu51Gln

p.E51Q

P01909

protein_coding

deleterious(0.03)

probably_damaging(1)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

HLA-DQA1

SNV

Missense_Mutation

c.157G>C

p.Asp53His

p.D53H

P01909

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HLA-DQA1

SNV

Missense_Mutation

rs368821483

c.367N>A

p.Val123Met

p.V123M

P01909

protein_coding

deleterious(0.01)

benign(0.078)

TCGA-EI-6509-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

folfox

HLA-DQA1

SNV

Missense_Mutation

novel

c.352N>C

p.Phe118Leu

p.F118L

P01909

protein_coding

tolerated(0.4)

benign(0.062)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

HLA-DQA1

SNV

Missense_Mutation

c.155N>G

p.Phe52Cys

p.F52C

P01909

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

HLA-DQA1

SNV

Missense_Mutation

c.621N>T

p.Glu207Asp

p.E207D

P01909

protein_coding

tolerated(0.1)

benign(0.003)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

HLA-DQA1

SNV

Missense_Mutation

novel

c.596N>T

p.Pro199Leu

p.P199L

P01909

protein_coding

deleterious(0.02)

benign(0.426)

TCGA-E6-A1LX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

HLA-DQA1

SNV

Missense_Mutation

novel

c.505N>A

p.His169Asn

p.H169N

P01909

protein_coding

tolerated(0.19)

possibly_damaging(0.629)

TCGA-EO-A22X-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unspecific

Carboplatin

Complete Response

HLA-DQA1

SNV

Missense_Mutation

novel

c.481N>G

p.Thr161Ala

p.T161A

P01909

protein_coding

deleterious(0.02)

possibly_damaging(0.471)

TCGA-EO-A3B0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

HLA-DQA1

SNV

Missense_Mutation

novel

c.727N>A

p.Leu243Met

p.L243M

P01909

protein_coding

tolerated(0.49)

probably_damaging(0.979)

TCGA-FI-A2F4-01

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
3117	HLA-DQA1	CLINICALLY ACTIONABLE		LYMPHOKINES		2166625
3117	HLA-DQA1	CLINICALLY ACTIONABLE		mercaptopurine	MERCAPTOPURINE	25217962
3117	HLA-DQA1	CLINICALLY ACTIONABLE		interferon beta-1b		21502966
3117	HLA-DQA1	CLINICALLY ACTIONABLE		Lapatinib	LAPATINIB
3117	HLA-DQA1	CLINICALLY ACTIONABLE		interferon beta-1a		21502966
3117	HLA-DQA1	CLINICALLY ACTIONABLE		azathioprine	AZATHIOPRINE	25217962
3117	HLA-DQA1	CLINICALLY ACTIONABLE		Drugs For Treatment Of Tuberculosis		12359646
3117	HLA-DQA1	CLINICALLY ACTIONABLE		lumiracoxib	LUMIRACOXIB	20639878
3117	HLA-DQA1	CLINICALLY ACTIONABLE		lapatinib	LAPATINIB	24687830,21245432

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