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: ASAP1

Gene summary for ASAP1

Gene summary.

Gene information	Species	Human
	Gene symbol	ASAP1
	Gene ID	50807
	Gene name	ArfGAP with SH3 domain, ankyrin repeat and PH domain 1
	Gene Alias	AMAP1
	Cytomap	8q24.21-q24.22
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	A0A0A0MRE5

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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
50807	ASAP1	CCI_1	Human	Cervix	CC	1.43e-12	1.18e+00	0.528
50807	ASAP1	CCI_2	Human	Cervix	CC	1.50e-16	1.70e+00	0.5249
50807	ASAP1	CCI_3	Human	Cervix	CC	7.90e-21	1.23e+00	0.516
50807	ASAP1	CCII_1	Human	Cervix	CC	6.21e-06	3.72e-01	0.3249
50807	ASAP1	AEH-subject1	Human	Endometrium	AEH	5.01e-18	4.73e-01	-0.3059
50807	ASAP1	AEH-subject2	Human	Endometrium	AEH	5.60e-08	3.70e-01	-0.2525
50807	ASAP1	AEH-subject3	Human	Endometrium	AEH	8.53e-15	4.38e-01	-0.2576
50807	ASAP1	AEH-subject4	Human	Endometrium	AEH	2.12e-13	4.83e-01	-0.2657
50807	ASAP1	AEH-subject5	Human	Endometrium	AEH	3.54e-08	3.82e-01	-0.2953
50807	ASAP1	EEC-subject1	Human	Endometrium	EEC	8.24e-20	6.23e-01	-0.2682
50807	ASAP1	EEC-subject2	Human	Endometrium	EEC	8.02e-12	4.57e-01	-0.2607
50807	ASAP1	EEC-subject3	Human	Endometrium	EEC	2.95e-11	2.92e-01	-0.2525
50807	ASAP1	EEC-subject4	Human	Endometrium	EEC	5.51e-15	4.36e-01	-0.2571
50807	ASAP1	EEC-subject5	Human	Endometrium	EEC	5.78e-03	2.23e-01	-0.249
50807	ASAP1	GSM5276937	Human	Endometrium	EEC	1.48e-03	2.96e-01	-0.0897
50807	ASAP1	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	6.78e-09	6.66e-02	-0.1869
50807	ASAP1	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	6.67e-12	-3.41e-02	-0.1875
50807	ASAP1	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	5.34e-13	4.35e-02	-0.1883
50807	ASAP1	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	3.28e-12	1.06e-01	-0.1934
50807	ASAP1	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	2.11e-21	-4.68e-02	-0.1917

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:00430877	Cervix	CC	regulation of GTPase activity	79/2311	348/18723	4.21e-08	2.60e-06	79
GO:00163587	Cervix	CC	dendrite development	58/2311	243/18723	4.52e-07	1.76e-05	58
GO:003133410	Cervix	CC	positive regulation of protein-containing complex assembly	55/2311	237/18723	2.25e-06	6.73e-05	55
GO:00609965	Cervix	CC	dendritic spine development	28/2311	99/18723	1.61e-05	3.15e-04	28
GO:00435476	Cervix	CC	positive regulation of GTPase activity	53/2311	255/18723	8.72e-05	1.16e-03	53
GO:00609984	Cervix	CC	regulation of dendritic spine development	18/2311	61/18723	2.84e-04	3.07e-03	18
GO:19021153	Cervix	CC	regulation of organelle assembly	40/2311	186/18723	2.92e-04	3.15e-03	40
GO:19021171	Cervix	CC	positive regulation of organelle assembly	19/2311	67/18723	3.42e-04	3.58e-03	19
GO:00070092	Cervix	CC	plasma membrane organization	28/2311	142/18723	7.85e-03	4.14e-02	28
GO:004325416	Endometrium	AEH	regulation of protein-containing complex assembly	83/2100	428/18723	3.90e-07	1.63e-05	83
GO:003133416	Endometrium	AEH	positive regulation of protein-containing complex assembly	52/2100	237/18723	1.43e-06	4.60e-05	52
GO:00430878	Endometrium	AEH	regulation of GTPase activity	66/2100	348/18723	1.26e-05	2.77e-04	66
GO:00435477	Endometrium	AEH	positive regulation of GTPase activity	48/2100	255/18723	2.18e-04	2.67e-03	48
GO:00163588	Endometrium	AEH	dendrite development	46/2100	243/18723	2.56e-04	3.03e-03	46
GO:004325417	Endometrium	EEC	regulation of protein-containing complex assembly	83/2168	428/18723	1.44e-06	4.64e-05	83
GO:003133417	Endometrium	EEC	positive regulation of protein-containing complex assembly	52/2168	237/18723	3.68e-06	9.90e-05	52
GO:004308712	Endometrium	EEC	regulation of GTPase activity	67/2168	348/18723	1.84e-05	3.43e-04	67
GO:004354712	Endometrium	EEC	positive regulation of GTPase activity	50/2168	255/18723	1.26e-04	1.66e-03	50
GO:001635813	Endometrium	EEC	dendrite development	44/2168	243/18723	1.72e-03	1.34e-02	44

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414418	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa0466612	Cervix	CC	Fc gamma R-mediated phagocytosis	31/1267	97/8465	1.78e-05	1.42e-04	8.40e-05	31
hsa0414419	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa0466613	Cervix	CC	Fc gamma R-mediated phagocytosis	31/1267	97/8465	1.78e-05	1.42e-04	8.40e-05	31
hsa0414420	Endometrium	AEH	Endocytosis	56/1197	251/8465	2.58e-04	2.15e-03	1.57e-03	56
hsa0466614	Endometrium	AEH	Fc gamma R-mediated phagocytosis	27/1197	97/8465	3.02e-04	2.39e-03	1.75e-03	27
hsa04144110	Endometrium	AEH	Endocytosis	56/1197	251/8465	2.58e-04	2.15e-03	1.57e-03	56
hsa0466615	Endometrium	AEH	Fc gamma R-mediated phagocytosis	27/1197	97/8465	3.02e-04	2.39e-03	1.75e-03	27
hsa0414424	Endometrium	EEC	Endocytosis	57/1237	251/8465	3.34e-04	2.82e-03	2.10e-03	57
hsa0466621	Endometrium	EEC	Fc gamma R-mediated phagocytosis	27/1237	97/8465	5.15e-04	3.83e-03	2.85e-03	27
hsa0414434	Endometrium	EEC	Endocytosis	57/1237	251/8465	3.34e-04	2.82e-03	2.10e-03	57
hsa0466631	Endometrium	EEC	Fc gamma R-mediated phagocytosis	27/1237	97/8465	5.15e-04	3.83e-03	2.85e-03	27
hsa04144210	Esophagus	ESCC	Endocytosis	186/4205	251/8465	9.74e-16	4.66e-14	2.39e-14	186
hsa0466620	Esophagus	ESCC	Fc gamma R-mediated phagocytosis	63/4205	97/8465	1.63e-03	4.89e-03	2.50e-03	63
hsa0414437	Esophagus	ESCC	Endocytosis	186/4205	251/8465	9.74e-16	4.66e-14	2.39e-14	186
hsa04666110	Esophagus	ESCC	Fc gamma R-mediated phagocytosis	63/4205	97/8465	1.63e-03	4.89e-03	2.50e-03	63
hsa0414422	Liver	HCC	Endocytosis	178/4020	251/8465	2.03e-14	5.22e-13	2.91e-13	178
hsa0466610	Liver	HCC	Fc gamma R-mediated phagocytosis	58/4020	97/8465	9.65e-03	2.52e-02	1.40e-02	58
hsa0414432	Liver	HCC	Endocytosis	178/4020	251/8465	2.03e-14	5.22e-13	2.91e-13	178
hsa0466611	Liver	HCC	Fc gamma R-mediated phagocytosis	58/4020	97/8465	9.65e-03	2.52e-02	1.40e-02	58

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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

ASAP1

SNV

Missense_Mutation

c.727T>G

p.Tyr243Asp

p.Y243D

Q9ULH1

protein_coding

deleterious(0)

possibly_damaging(0.622)

TCGA-A8-A09I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

ASAP1

SNV

Missense_Mutation

c.2701N>A

p.Val901Met

p.V901M

Q9ULH1

protein_coding

tolerated(0.13)

probably_damaging(0.994)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ASAP1

SNV

Missense_Mutation

novel

c.2365N>A

p.Glu789Lys

p.E789K

Q9ULH1

protein_coding

tolerated(0.42)

benign(0.03)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ASAP1

SNV

Missense_Mutation

novel

c.489N>C

p.Lys163Asn

p.K163N

Q9ULH1

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ASAP1

SNV

Missense_Mutation

c.1705N>A

p.Glu569Lys

p.E569K

Q9ULH1

protein_coding

deleterious(0.03)

benign(0.005)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ASAP1

SNV

Missense_Mutation

c.2503N>G

p.Lys835Glu

p.K835E

Q9ULH1

protein_coding

deleterious(0.04)

probably_damaging(0.971)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ASAP1

SNV

Missense_Mutation

c.403N>G

p.Leu135Val

p.L135V

Q9ULH1

protein_coding

deleterious(0.04)

benign(0.1)

TCGA-E9-A1R2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

ASAP1

SNV

Missense_Mutation

novel

c.1148N>G

p.Lys383Arg

p.K383R

Q9ULH1

protein_coding

tolerated(0.14)

probably_damaging(0.996)

TCGA-LQ-A4E4-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

ASAP1

insertion

Frame_Shift_Ins

novel

c.3206_3207insATGTACTTTACCCATGGTATCATGTAACCTTGTGAGTTGTAGGC

p.Arg1070CysfsTer18

p.R1070Cfs*18

Q9ULH1

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

ASAP1

insertion

Nonsense_Mutation

novel

c.310_311insTATGAC

p.Ser104delinsIleTerArg

p.S104delinsI*R

Q9ULH1

protein_coding

TCGA-AC-A3QQ-01

Breast

breast invasive 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

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