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: AP1S1

Gene summary for AP1S1

Gene summary.

Gene information	Species	Human
	Gene symbol	AP1S1
	Gene ID	1174
	Gene name	adaptor related protein complex 1 subunit sigma 1
	Gene Alias	AP19
	Cytomap	7q22.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	A0A024QYT6

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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
1174	AP1S1	GSM4909286	Human	Breast	IDC	2.31e-17	4.57e-01	0.1081
1174	AP1S1	GSM4909288	Human	Breast	IDC	4.58e-03	3.49e-02	0.0988
1174	AP1S1	GSM4909293	Human	Breast	IDC	6.46e-09	3.11e-01	0.1581
1174	AP1S1	GSM4909294	Human	Breast	IDC	4.50e-04	2.78e-01	0.2022
1174	AP1S1	GSM4909296	Human	Breast	IDC	2.13e-05	2.56e-01	0.1524
1174	AP1S1	GSM4909297	Human	Breast	IDC	3.00e-03	-8.60e-02	0.1517
1174	AP1S1	GSM4909304	Human	Breast	IDC	3.72e-11	3.18e-01	0.1636
1174	AP1S1	GSM4909308	Human	Breast	IDC	1.52e-02	2.45e-01	0.158
1174	AP1S1	GSM4909311	Human	Breast	IDC	5.96e-10	-9.67e-02	0.1534
1174	AP1S1	GSM4909312	Human	Breast	IDC	1.22e-07	2.42e-01	0.1552
1174	AP1S1	GSM4909315	Human	Breast	IDC	8.22e-17	5.48e-01	0.21
1174	AP1S1	GSM4909316	Human	Breast	IDC	2.84e-03	2.73e-01	0.21
1174	AP1S1	GSM4909319	Human	Breast	IDC	2.20e-21	-4.44e-02	0.1563
1174	AP1S1	GSM4909320	Human	Breast	IDC	2.67e-04	-5.57e-02	0.1575
1174	AP1S1	GSM4909321	Human	Breast	IDC	1.54e-06	5.44e-02	0.1559
1174	AP1S1	brca1	Human	Breast	Precancer	1.15e-04	3.82e-01	-0.0338
1174	AP1S1	brca2	Human	Breast	Precancer	1.28e-05	2.53e-01	-0.024
1174	AP1S1	brca3	Human	Breast	Precancer	1.01e-06	2.71e-01	-0.0263
1174	AP1S1	M2	Human	Breast	IDC	1.92e-03	2.26e-01	0.21
1174	AP1S1	NCCBC14	Human	Breast	DCIS	5.71e-05	2.32e-01	0.2021

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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
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
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
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
Cervix	N_HPV
Endometrium	AEH
Endometrium	EEC
Prostate	BPH
Prostate	Tumor

∗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:00068986	Breast	Precancer	receptor-mediated endocytosis	27/1080	244/18723	9.01e-04	1.03e-02	27
GO:000689813	Breast	IDC	receptor-mediated endocytosis	35/1434	244/18723	2.38e-04	3.75e-03	35
GO:00096157	Breast	IDC	response to virus	47/1434	367/18723	3.53e-04	5.16e-03	47
GO:000689823	Breast	DCIS	receptor-mediated endocytosis	35/1390	244/18723	1.31e-04	2.25e-03	35
GO:000961512	Breast	DCIS	response to virus	45/1390	367/18723	6.16e-04	7.82e-03	45
GO:0006898	Colorectum	AD	receptor-mediated endocytosis	76/3918	244/18723	1.07e-04	1.59e-03	76
GO:00068981	Colorectum	MSS	receptor-mediated endocytosis	69/3467	244/18723	1.18e-04	1.82e-03	69
GO:00068983	Colorectum	CRC	receptor-mediated endocytosis	50/2078	244/18723	1.27e-05	4.08e-04	50
GO:000961517	Esophagus	HGIN	response to virus	69/2587	367/18723	4.39e-03	3.86e-02	69
GO:000961518	Esophagus	ESCC	response to virus	238/8552	367/18723	6.65e-14	3.32e-12	238
GO:000689818	Esophagus	ESCC	receptor-mediated endocytosis	142/8552	244/18723	5.22e-05	4.05e-04	142
GO:000689811	Liver	Cirrhotic	receptor-mediated endocytosis	91/4634	244/18723	8.13e-06	1.22e-04	91
GO:00096155	Liver	Cirrhotic	response to virus	126/4634	367/18723	2.10e-05	2.77e-04	126
GO:000961511	Liver	HCC	response to virus	210/7958	367/18723	7.32e-09	1.86e-07	210
GO:000689821	Liver	HCC	receptor-mediated endocytosis	134/7958	244/18723	5.73e-05	5.31e-04	134
GO:000961515	Oral cavity	OSCC	response to virus	215/7305	367/18723	1.63e-14	9.41e-13	215
GO:000689810	Oral cavity	OSCC	receptor-mediated endocytosis	125/7305	244/18723	6.56e-05	5.32e-04	125
GO:000961516	Oral cavity	LP	response to virus	143/4623	367/18723	7.42e-10	3.52e-08	143
GO:000689817	Oral cavity	LP	receptor-mediated endocytosis	87/4623	244/18723	7.83e-05	1.02e-03	87
GO:000961510	Prostate	BPH	response to virus	99/3107	367/18723	2.82e-07	6.07e-06	99

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517014	Breast	IDC	Human immunodeficiency virus 1 infection	33/867	212/8465	9.28e-03	4.37e-02	3.27e-02	33
hsa0517015	Breast	IDC	Human immunodeficiency virus 1 infection	33/867	212/8465	9.28e-03	4.37e-02	3.27e-02	33
hsa0517024	Breast	DCIS	Human immunodeficiency virus 1 infection	33/846	212/8465	6.49e-03	3.22e-02	2.37e-02	33
hsa0517034	Breast	DCIS	Human immunodeficiency virus 1 infection	33/846	212/8465	6.49e-03	3.22e-02	2.37e-02	33
hsa05170	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051701	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051702	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa04142	Colorectum	SER	Lysosome	38/1580	132/8465	2.87e-03	2.03e-02	1.47e-02	38
hsa051703	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa041421	Colorectum	SER	Lysosome	38/1580	132/8465	2.87e-03	2.03e-02	1.47e-02	38
hsa051704	Colorectum	MSS	Human immunodeficiency virus 1 infection	69/1875	212/8465	2.66e-04	1.98e-03	1.21e-03	69
hsa051705	Colorectum	MSS	Human immunodeficiency virus 1 infection	69/1875	212/8465	2.66e-04	1.98e-03	1.21e-03	69
hsa0517029	Esophagus	HGIN	Human immunodeficiency virus 1 infection	51/1383	212/8465	2.16e-03	1.90e-02	1.51e-02	51
hsa041426	Esophagus	HGIN	Lysosome	33/1383	132/8465	6.65e-03	4.37e-02	3.47e-02	33
hsa05170112	Esophagus	HGIN	Human immunodeficiency virus 1 infection	51/1383	212/8465	2.16e-03	1.90e-02	1.51e-02	51
hsa0414213	Esophagus	HGIN	Lysosome	33/1383	132/8465	6.65e-03	4.37e-02	3.47e-02	33
hsa0414222	Esophagus	ESCC	Lysosome	102/4205	132/8465	5.11e-11	7.13e-10	3.65e-10	102
hsa05170210	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa0414232	Esophagus	ESCC	Lysosome	102/4205	132/8465	5.11e-11	7.13e-10	3.65e-10	102
hsa0517038	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147

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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

AP1S1

insertion

Nonsense_Mutation

novel

c.159_160insCTTGCATAACTAGTAGAGCCAGGATTTGAACCCAGCT

p.Asp54LeufsTer3

p.D54Lfs*3

P61966

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

AP1S1

insertion

In_Frame_Ins

novel

c.253_254insCCTTCTCCTCGGAGCAGGTAAATTACTTGGCTCAGGTTTTTGCTG

p.His85delinsProPheSerSerGluGlnValAsnTyrLeuAlaGlnValPheAlaAsp

p.H85delinsPFSSEQVNYLAQVFAD

P61966

protein_coding

TCGA-B6-A0I5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AP1S1

SNV

Missense_Mutation

novel

c.158G>T

p.Arg53Met

p.R53M

P61966

protein_coding

deleterious(0.01)

benign(0.321)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

AP1S1

SNV

Missense_Mutation

rs754050754

c.83N>A

p.Arg28Gln

p.R28Q

P61966

protein_coding

deleterious(0)

benign(0.066)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

AP1S1

SNV

Missense_Mutation

novel

c.407N>G

p.Glu136Gly

p.E136G

P61966

protein_coding

tolerated(0.26)

benign(0)

TCGA-CM-5349-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

AP1S1

SNV

Missense_Mutation

novel

c.361G>A

p.Gly121Arg

p.G121R

P61966

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-F4-6570-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

AP1S1

SNV

Missense_Mutation

novel

c.350T>G

p.Phe117Cys

p.F117C

P61966

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

AP1S1

SNV

Missense_Mutation

rs760826610

c.71C>T

p.Ser24Leu

p.S24L

P61966

protein_coding

tolerated(0.1)

benign(0.013)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

AP1S1

SNV

Missense_Mutation

c.28C>T

p.Arg10Trp

p.R10W

P61966

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

AP1S1

SNV

Missense_Mutation

novel

c.440N>T

p.Ser147Leu

p.S147L

P61966

protein_coding

tolerated(0.42)

benign(0)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

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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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