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: TAP1

Gene summary for TAP1

Gene summary.

Gene information	Species	Human
	Gene symbol	TAP1
	Gene ID	6890
	Gene name	transporter 1, ATP binding cassette subfamily B member
	Gene Alias	ABC17
	Cytomap	6p21.32
	Gene Type	protein-coding
	GO ID	GO:0002250
	UniProtAcc	A0A0S2Z5A6

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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
6890	TAP1	GSM4909281	Human	Breast	IDC	1.31e-36	8.59e-01	0.21
6890	TAP1	GSM4909282	Human	Breast	IDC	1.83e-05	2.58e-01	-0.0288
6890	TAP1	GSM4909286	Human	Breast	IDC	8.25e-07	-1.49e-01	0.1081
6890	TAP1	GSM4909287	Human	Breast	IDC	9.14e-03	2.97e-01	0.2057
6890	TAP1	GSM4909311	Human	Breast	IDC	4.13e-07	-1.07e-01	0.1534
6890	TAP1	GSM4909312	Human	Breast	IDC	1.07e-02	-1.02e-01	0.1552
6890	TAP1	GSM4909319	Human	Breast	IDC	4.43e-07	-8.40e-02	0.1563
6890	TAP1	GSM4909321	Human	Breast	IDC	2.44e-04	6.34e-02	0.1559
6890	TAP1	NCCBC14	Human	Breast	DCIS	3.39e-04	-1.35e-01	0.2021
6890	TAP1	NCCBC5	Human	Breast	DCIS	2.38e-09	3.71e-01	0.2046
6890	TAP1	P1	Human	Breast	IDC	1.29e-04	1.19e-01	0.1527
6890	TAP1	P2	Human	Breast	IDC	1.99e-03	3.34e-01	0.21
6890	TAP1	DCIS2	Human	Breast	DCIS	4.39e-11	-1.53e-03	0.0085
6890	TAP1	CA_HPV_1	Human	Cervix	CC	1.64e-11	5.05e-01	0.0264
6890	TAP1	CCI_2	Human	Cervix	CC	3.56e-06	6.39e-01	0.5249
6890	TAP1	Tumor	Human	Cervix	CC	1.35e-20	5.88e-01	0.1241
6890	TAP1	sample1	Human	Cervix	CC	4.61e-08	5.41e-01	0.0959
6890	TAP1	sample3	Human	Cervix	CC	6.39e-31	6.42e-01	0.1387
6890	TAP1	T1	Human	Cervix	CC	1.73e-15	5.27e-01	0.0918
6890	TAP1	T3	Human	Cervix	CC	7.18e-27	6.65e-01	0.1389

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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
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
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:000247813	Breast	IDC	antigen processing and presentation of exogenous peptide antigen	13/1434	38/18723	2.60e-06	1.01e-04	13
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:001988413	Breast	IDC	antigen processing and presentation of exogenous antigen	13/1434	47/18723	3.53e-05	8.08e-04	13
GO:00198829	Breast	IDC	antigen processing and presentation	20/1434	106/18723	1.41e-04	2.49e-03	20
GO:001988513	Breast	IDC	antigen processing and presentation of endogenous peptide antigen via MHC class I	7/1434	17/18723	1.49e-04	2.61e-03	7
GO:000247412	Breast	IDC	antigen processing and presentation of peptide antigen via MHC class I	8/1434	28/18723	9.00e-04	1.04e-02	8
GO:001583312	Breast	IDC	peptide transport	32/1434	264/18723	6.61e-03	4.62e-02	32
GO:004800222	Breast	DCIS	antigen processing and presentation of peptide antigen	20/1390	62/18723	1.01e-08	7.56e-07	20
GO:000247822	Breast	DCIS	antigen processing and presentation of exogenous peptide antigen	15/1390	38/18723	3.22e-08	2.09e-06	15
GO:001988422	Breast	DCIS	antigen processing and presentation of exogenous antigen	15/1390	47/18723	8.26e-07	3.39e-05	15
GO:000248323	Breast	DCIS	antigen processing and presentation of endogenous peptide antigen	9/1390	19/18723	3.11e-06	1.02e-04	9
GO:001988323	Breast	DCIS	antigen processing and presentation of endogenous antigen	10/1390	26/18723	8.68e-06	2.37e-04	10
GO:001988214	Breast	DCIS	antigen processing and presentation	22/1390	106/18723	8.76e-06	2.38e-04	22
GO:001988523	Breast	DCIS	antigen processing and presentation of endogenous peptide antigen via MHC class I	7/1390	17/18723	1.23e-04	2.12e-03	7
GO:000247422	Breast	DCIS	antigen processing and presentation of peptide antigen via MHC class I	9/1390	28/18723	1.26e-04	2.18e-03	9
GO:000247810	Cervix	CC	antigen processing and presentation of exogenous peptide antigen	18/2311	38/18723	1.20e-07	6.06e-06	18
GO:004800210	Cervix	CC	antigen processing and presentation of peptide antigen	24/2311	62/18723	1.21e-07	6.07e-06	24
GO:001988410	Cervix	CC	antigen processing and presentation of exogenous antigen	20/2311	47/18723	2.18e-07	9.57e-06	20

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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
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
hsa0516324	Breast	IDC	Human cytomegalovirus infection	39/867	225/8465	6.66e-04	5.41e-03	4.05e-03	39
hsa0517014	Breast	IDC	Human immunodeficiency virus 1 infection	33/867	212/8465	9.28e-03	4.37e-02	3.27e-02	33
hsa0516932	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0461233	Breast	IDC	Antigen processing and presentation	24/867	78/8465	4.61e-07	8.33e-06	6.23e-06	24
hsa0414532	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0516334	Breast	IDC	Human cytomegalovirus infection	39/867	225/8465	6.66e-04	5.41e-03	4.05e-03	39
hsa0517015	Breast	IDC	Human immunodeficiency virus 1 infection	33/867	212/8465	9.28e-03	4.37e-02	3.27e-02	33
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
hsa0516344	Breast	DCIS	Human cytomegalovirus infection	38/846	225/8465	8.11e-04	5.95e-03	4.38e-03	38
hsa0517024	Breast	DCIS	Human immunodeficiency virus 1 infection	33/846	212/8465	6.49e-03	3.22e-02	2.37e-02	33
hsa0516951	Breast	DCIS	Epstein-Barr virus infection	46/846	202/8465	5.60e-08	1.13e-06	8.33e-07	46
hsa0461252	Breast	DCIS	Antigen processing and presentation	25/846	78/8465	6.75e-08	1.28e-06	9.45e-07	25
hsa0414551	Breast	DCIS	Phagosome	35/846	152/8465	1.67e-06	2.45e-05	1.81e-05	35
hsa0516354	Breast	DCIS	Human cytomegalovirus infection	38/846	225/8465	8.11e-04	5.95e-03	4.38e-03	38
hsa0517034	Breast	DCIS	Human immunodeficiency virus 1 infection	33/846	212/8465	6.49e-03	3.22e-02	2.37e-02	33

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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

TAP1

SNV

Missense_Mutation

novel

c.516G>C

p.Leu172Phe

p.L172F

Q03518

protein_coding

tolerated(0.05)

benign(0.261)

TCGA-A2-A0D4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TAP1

SNV

Missense_Mutation

novel

c.1356A>C

p.Glu452Asp

p.E452D

Q03518

protein_coding

tolerated(0.21)

benign(0.038)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TAP1

SNV

Missense_Mutation

c.1601N>A

p.Ser534Tyr

p.S534Y

Q03518

protein_coding

deleterious(0)

possibly_damaging(0.578)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

TAP1

insertion

Nonsense_Mutation

novel

c.591_592insCTCCTCTCTTGGTAAGGGGAACGCAGGGCAAGAGGGGAGGAC

p.Pro197_Thr198insLeuLeuSerTrpTerGlyGluArgArgAlaArgGlyGluAsp

p.P197_T198insLLSW*GERRARGED

Q03518

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TAP1

SNV

Missense_Mutation

rs550037204

c.809G>A

p.Arg270His

p.R270H

Q03518

protein_coding

tolerated(0.07)

benign(0.115)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TAP1

SNV

Missense_Mutation

rs777683307

c.1336N>A

p.Glu446Lys

p.E446K

Q03518

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-C5-A8XK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TAP1

SNV

Missense_Mutation

c.2200G>A

p.Asp734Asn

p.D734N

Q03518

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TAP1

SNV

Missense_Mutation

c.1099C>A

p.Leu367Met

p.L367M

Q03518

protein_coding

tolerated(0.56)

benign(0.225)

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TAP1

SNV

Missense_Mutation

c.473N>A

p.Pro158Gln

p.P158Q

Q03518

protein_coding

deleterious(0.02)

possibly_damaging(0.823)

TCGA-A6-6780-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TAP1

SNV

Missense_Mutation

c.1115G>A

p.Arg372Gln

p.R372Q

Q03518

protein_coding

deleterious(0)

probably_damaging(1)

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

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