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-DRB1

Gene summary for HLA-DRB1

Gene summary.

Gene information	Species	Human
	Gene symbol	HLA-DRB1
	Gene ID	3123
	Gene name	major histocompatibility complex, class II, DR beta 1
	Gene Alias	DRB1
	Cytomap	6p21.32
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P01912

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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
3123	HLA-DRB1	GSM4909282	Human	Breast	IDC	1.51e-02	3.15e-01	-0.0288
3123	HLA-DRB1	GSM4909285	Human	Breast	IDC	1.96e-04	-2.42e-01	0.21
3123	HLA-DRB1	GSM4909286	Human	Breast	IDC	2.89e-06	-2.58e-01	0.1081
3123	HLA-DRB1	GSM4909287	Human	Breast	IDC	6.75e-23	8.67e-01	0.2057
3123	HLA-DRB1	GSM4909290	Human	Breast	IDC	8.74e-04	3.56e-01	0.2096
3123	HLA-DRB1	GSM4909297	Human	Breast	IDC	1.01e-03	-1.62e-01	0.1517
3123	HLA-DRB1	GSM4909300	Human	Breast	IDC	3.03e-02	4.67e-01	0.0334
3123	HLA-DRB1	GSM4909304	Human	Breast	IDC	1.53e-04	-1.88e-01	0.1636
3123	HLA-DRB1	GSM4909311	Human	Breast	IDC	4.37e-06	-2.09e-01	0.1534
3123	HLA-DRB1	GSM4909312	Human	Breast	IDC	9.64e-08	-2.58e-01	0.1552
3123	HLA-DRB1	GSM4909319	Human	Breast	IDC	2.78e-09	-1.75e-03	0.1563
3123	HLA-DRB1	GSM4909320	Human	Breast	IDC	3.11e-02	-2.73e-01	0.1575
3123	HLA-DRB1	GSM4909321	Human	Breast	IDC	1.65e-02	-9.00e-02	0.1559
3123	HLA-DRB1	ctrl6	Human	Breast	Precancer	3.95e-02	3.99e-01	-0.0061
3123	HLA-DRB1	NCCBC11	Human	Breast	DCIS	1.93e-06	6.44e-01	0.1232
3123	HLA-DRB1	NCCBC3	Human	Breast	DCIS	3.23e-49	1.27e+00	0.1198
3123	HLA-DRB1	NCCBC5	Human	Breast	DCIS	1.55e-16	7.97e-01	0.2046
3123	HLA-DRB1	P2	Human	Breast	IDC	5.02e-21	9.64e-01	0.21
3123	HLA-DRB1	CA_HPV_1	Human	Cervix	CC	1.02e-25	7.37e-01	0.0264
3123	HLA-DRB1	CA_HPV_3	Human	Cervix	CC	1.41e-04	-5.51e-01	0.0414

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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:005122216	Endometrium	EEC	positive regulation of protein transport	66/2168	303/18723	2.55e-07	1.09e-05	66
GO:004671817	Endometrium	EEC	viral entry into host cell	38/2168	144/18723	7.19e-07	2.58e-05	38
GO:004440917	Endometrium	EEC	entry into host	39/2168	151/18723	9.34e-07	3.22e-05	39
GO:007133314	Endometrium	EEC	cellular response to glucose stimulus	39/2168	151/18723	9.34e-07	3.22e-05	39
GO:007133114	Endometrium	EEC	cellular response to hexose stimulus	39/2168	153/18723	1.33e-06	4.35e-05	39
GO:007132614	Endometrium	EEC	cellular response to monosaccharide stimulus	39/2168	154/18723	1.59e-06	4.96e-05	39
GO:004259314	Endometrium	EEC	glucose homeostasis	56/2168	258/18723	2.26e-06	6.61e-05	56
GO:003350014	Endometrium	EEC	carbohydrate homeostasis	56/2168	259/18723	2.56e-06	7.39e-05	56
GO:005079217	Endometrium	EEC	regulation of viral process	40/2168	164/18723	3.24e-06	8.85e-05	40
GO:004341011	Endometrium	EEC	positive regulation of MAPK cascade	89/2168	480/18723	4.21e-06	1.08e-04	89
GO:002240715	Endometrium	EEC	regulation of cell-cell adhesion	84/2168	448/18723	4.98e-06	1.24e-04	84
GO:004312216	Endometrium	EEC	regulation of I-kappaB kinase/NF-kappaB signaling	53/2168	249/18723	7.59e-06	1.73e-04	53
GO:000250114	Endometrium	EEC	peptide antigen assembly with MHC protein complex	10/2168	18/18723	7.70e-06	1.75e-04	10
GO:000247816	Endometrium	EEC	antigen processing and presentation of exogenous peptide antigen	15/2168	38/18723	9.82e-06	2.16e-04	15
GO:001988416	Endometrium	EEC	antigen processing and presentation of exogenous antigen	17/2168	47/18723	1.02e-05	2.22e-04	17
GO:190390017	Endometrium	EEC	regulation of viral life cycle	36/2168	148/18723	1.05e-05	2.25e-04	36
GO:001988615	Endometrium	EEC	antigen processing and presentation of exogenous peptide antigen via MHC class II	13/2168	30/18723	1.15e-05	2.40e-04	13
GO:000239614	Endometrium	EEC	MHC protein complex assembly	10/2168	19/18723	1.46e-05	2.87e-04	10
GO:004312314	Endometrium	EEC	positive regulation of I-kappaB kinase/NF-kappaB signaling	42/2168	186/18723	1.47e-05	2.87e-04	42
GO:000724915	Endometrium	EEC	I-kappaB kinase/NF-kappaB signaling	57/2168	281/18723	1.60e-05	3.12e-04	57

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
hsa0414518	Breast	Precancer	Phagosome	27/684	152/8465	7.37e-05	6.85e-04	5.25e-04	27
hsa0532312	Breast	Precancer	Rheumatoid arthritis	19/684	93/8465	1.30e-04	1.14e-03	8.73e-04	19
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
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
hsa0414519	Breast	Precancer	Phagosome	27/684	152/8465	7.37e-05	6.85e-04	5.25e-04	27
hsa0532313	Breast	Precancer	Rheumatoid arthritis	19/684	93/8465	1.30e-04	1.14e-03	8.73e-04	19
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
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
hsa0414522	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0541623	Breast	IDC	Viral myocarditis	18/867	60/8465	1.85e-05	2.01e-04	1.50e-04	18
hsa0516624	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0532321	Breast	IDC	Rheumatoid arthritis	21/867	93/8465	3.69e-04	3.15e-03	2.36e-03	21
hsa0494014	Breast	IDC	Type I diabetes mellitus	12/867	43/8465	9.40e-04	7.28e-03	5.44e-03	12
hsa0533012	Breast	IDC	Allograft rejection	11/867	38/8465	1.09e-03	8.26e-03	6.18e-03	11

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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-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Breast	DCIS
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Breast	Healthy
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Breast	IDC
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Cervix	ADJ
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Cervix	CC
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Cervix	Healthy
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Cervix	Precancer
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	CRC	AD
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	CRC	ADJ
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	CRC	FAP
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	CRC	MSI-H
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	CRC	MSS
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	CRC	SER
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Endometrium	ADJ
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Endometrium	AEH
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Endometrium	EEC
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	Endometrium	Healthy
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	HNSCC	ADJ
HLA-DRB1	CD4	HLA-DRB1_CD4	MHC-II	HNSCC	Healthy
HLA-DRB1	CD4	HLA-DRB1_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-DRB1

SNV

Missense_Mutation

rs754953589

c.202C>T

p.Arg68Cys

p.R68C

P04229,Q9GIY3,P01911,Q29974

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HLA-DRB1

SNV

Missense_Mutation

rs761045049

c.100C>T

p.Pro34Ser

p.P34S

P04229,Q9GIY3,P01911,Q29974

protein_coding

tolerated(0.24)

benign(0)

TCGA-G5-6641-01

Colorectum

rectum adenocarcinoma

Male

>=65

III/IV

Chemotherapy

oxaliplatin

HLA-DRB1

SNV

Missense_Mutation

novel

c.330C>A

p.His110Gln

p.H110Q

P04229,Q9GIY3,P01911,Q29974

protein_coding

deleterious(0.03)

possibly_damaging(0.735)

TCGA-AP-A054-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

HLA-DRB1

SNV

Missense_Mutation

novel

c.380A>T

p.Lys127Met

p.K127M

P04229,Q9GIY3,P01911,Q29974

protein_coding

tolerated(0.11)

benign(0.376)

TCGA-DF-A2KS-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HLA-DRB1

SNV

Missense_Mutation

novel

c.154N>T

p.Arg52Trp

p.R52W

P04229,Q9GIY3,P01911,Q29974

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-PG-A6IB-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HLA-DRB1

SNV

Missense_Mutation

novel

c.460G>C

p.Gly154Arg

p.G154R

P04229,Q9GIY3,P01911,Q29974

protein_coding

deleterious(0.03)

probably_damaging(0.986)

TCGA-34-2609-01

Lung

lung squamous cell carcinoma

Male

>=65

I/II

Chemotherapy

gemcitabine

HLA-DRB1

SNV

Missense_Mutation

c.469G>A

p.Glu157Lys

p.E157K

P04229,Q9GIY3,P01911,Q29974

protein_coding

tolerated(0.41)

probably_damaging(0.996)

TCGA-37-3789-01

Lung

lung squamous cell carcinoma

Male

>=65

I/II

Unknown

HLA-DRB1

SNV

Missense_Mutation

rs17885257

c.235N>T

p.Val79Leu

p.V79L

P04229,Q9GIY3,P01911,Q29974

protein_coding

tolerated(0.2)

probably_damaging(0.974)

TCGA-63-6202-01

Lung

lung squamous cell carcinoma

Male

Unknown

I/II

Unknown

HLA-DRB1

insertion

Frame_Shift_Ins

novel

c.331_332insCA

p.Asn111ThrfsTer19

p.N111Tfs*19

P04229,Q9GIY3,P01911,Q29974

protein_coding

TCGA-CN-A642-01

Oral cavity

head & neck squamous cell carcinoma

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
3123	HLA-DRB1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		flupirtine	FLUPIRTINE	26959717
3123	HLA-DRB1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		methimazole	METHIMAZOLE
3123	HLA-DRB1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		aspirin	ASPIRIN	15784113,19392989
3123	HLA-DRB1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		fluvastatin	FLUVASTATIN	27839692
3123	HLA-DRB1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		infliximab	INFLIXIMAB
3123	HLA-DRB1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		efavirenz	EFAVIRENZ	18301070
3123	HLA-DRB1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		adalimumab	ADALIMUMAB
3123	HLA-DRB1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		propylthiouracil	PROPYLTHIOURACIL
3123	HLA-DRB1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		Influenza vaccines		11756990
3123	HLA-DRB1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		Tumor necrosis factor alpha (TNF-alpha) inhibitors

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