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: AGL

Gene summary for AGL

Gene summary.

Gene information	Species	Human
	Gene symbol	AGL
	Gene ID	178
	Gene name	amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase
	Gene Alias	GDE
	Cytomap	1p21.2
	Gene Type	protein-coding
	GO ID	GO:0000271
	UniProtAcc	A0A0S2A4E4

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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
178	AGL	CCI_2	Human	Cervix	CC	3.47e-21	1.53e+00	0.5249
178	AGL	CCI_3	Human	Cervix	CC	3.04e-14	1.01e+00	0.516
178	AGL	LZE4T	Human	Esophagus	ESCC	4.15e-08	3.27e-01	0.0811
178	AGL	LZE7T	Human	Esophagus	ESCC	2.02e-02	3.58e-01	0.0667
178	AGL	LZE8T	Human	Esophagus	ESCC	2.41e-05	1.13e-01	0.067
178	AGL	LZE20T	Human	Esophagus	ESCC	3.43e-03	7.66e-02	0.0662
178	AGL	LZE24T	Human	Esophagus	ESCC	2.47e-03	7.60e-02	0.0596
178	AGL	P1T-E	Human	Esophagus	ESCC	2.06e-10	3.44e-01	0.0875
178	AGL	P2T-E	Human	Esophagus	ESCC	2.43e-27	5.20e-01	0.1177
178	AGL	P4T-E	Human	Esophagus	ESCC	2.43e-13	3.05e-01	0.1323
178	AGL	P5T-E	Human	Esophagus	ESCC	2.09e-19	1.91e-01	0.1327
178	AGL	P8T-E	Human	Esophagus	ESCC	2.00e-28	2.79e-01	0.0889
178	AGL	P9T-E	Human	Esophagus	ESCC	1.82e-14	2.68e-01	0.1131
178	AGL	P10T-E	Human	Esophagus	ESCC	1.10e-26	5.13e-01	0.116
178	AGL	P11T-E	Human	Esophagus	ESCC	4.50e-08	1.92e-01	0.1426
178	AGL	P12T-E	Human	Esophagus	ESCC	9.71e-32	6.89e-01	0.1122
178	AGL	P15T-E	Human	Esophagus	ESCC	5.05e-13	2.48e-01	0.1149
178	AGL	P16T-E	Human	Esophagus	ESCC	2.47e-13	1.40e-01	0.1153
178	AGL	P17T-E	Human	Esophagus	ESCC	4.03e-06	2.27e-01	0.1278
178	AGL	P20T-E	Human	Esophagus	ESCC	7.39e-11	3.13e-01	0.1124

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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
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:00075172	Breast	IDC	muscle organ development	38/1434	327/18723	6.63e-03	4.62e-02	38
GO:00075171	Breast	DCIS	muscle organ development	37/1390	327/18723	6.86e-03	4.75e-02	37
GO:00060919	Cervix	CC	generation of precursor metabolites and energy	105/2311	490/18723	7.40e-09	6.61e-07	105
GO:00159809	Cervix	CC	energy derivation by oxidation of organic compounds	74/2311	318/18723	3.83e-08	2.53e-06	74
GO:004854510	Cervix	CC	response to steroid hormone	74/2311	339/18723	5.71e-07	2.09e-05	74
GO:003166710	Cervix	CC	response to nutrient levels	92/2311	474/18723	5.80e-06	1.42e-04	92
GO:00319609	Cervix	CC	response to corticosteroid	39/2311	167/18723	5.48e-05	8.06e-04	39
GO:00513849	Cervix	CC	response to glucocorticoid	35/2311	148/18723	9.87e-05	1.27e-03	35
GO:00161977	Cervix	CC	endosomal transport	48/2311	230/18723	1.65e-04	1.97e-03	48
GO:00075846	Cervix	CC	response to nutrient	33/2311	174/18723	7.65e-03	4.07e-02	33
GO:0016197	Colorectum	AD	endosomal transport	90/3918	230/18723	1.88e-10	1.73e-08	90
GO:00161971	Colorectum	SER	endosomal transport	61/2897	230/18723	1.03e-05	3.35e-04	61
GO:00161972	Colorectum	MSS	endosomal transport	79/3467	230/18723	7.04e-09	4.39e-07	79
GO:00161973	Colorectum	FAP	endosomal transport	56/2622	230/18723	1.79e-05	4.53e-04	56
GO:00075174	Endometrium	AEH	muscle organ development	60/2100	327/18723	8.19e-05	1.22e-03	60
GO:000751712	Endometrium	EEC	muscle organ development	59/2168	327/18723	3.49e-04	3.85e-03	59
GO:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:2001233111	Esophagus	ESCC	regulation of apoptotic signaling pathway	256/8552	356/18723	4.11e-24	1.04e-21	256
GO:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0015980110	Esophagus	ESCC	energy derivation by oxidation of organic compounds	220/8552	318/18723	1.20e-17	1.09e-15	220

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

AGL

SNV

Missense_Mutation

c.526G>C

p.Ala176Pro

p.A176P

P35573

protein_coding

tolerated(0.1)

probably_damaging(0.922)

TCGA-A2-A0T0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

AGL

SNV

Missense_Mutation

novel

c.982N>A

p.Asp328Asn

p.D328N

P35573

protein_coding

tolerated(0.18)

benign(0.024)

TCGA-A7-A6VX-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

AGL

SNV

Missense_Mutation

novel

c.1243A>C

p.Lys415Gln

p.K415Q

P35573

protein_coding

tolerated(0.06)

possibly_damaging(0.566)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AGL

SNV

Missense_Mutation

c.3533N>T

p.Pro1178Leu

p.P1178L

P35573

protein_coding

deleterious(0.05)

benign(0.398)

TCGA-B6-A0RL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AGL

SNV

Missense_Mutation

novel

c.1391N>A

p.Gly464Glu

p.G464E

P35573

protein_coding

deleterious(0.01)

possibly_damaging(0.644)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

AGL

SNV

Missense_Mutation

novel

c.3550N>T

p.Pro1184Ser

p.P1184S

P35573

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-OL-A97C-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AGL

SNV

Missense_Mutation

rs147977213

c.2930G>T

p.Arg977Leu

p.R977L

P35573

protein_coding

tolerated(0.36)

benign(0.298)

TCGA-WT-AB41-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

AGL

deletion

Frame_Shift_Del

c.3794delN

p.Ser1266ValfsTer24

p.S1266Vfs*24

P35573

protein_coding

TCGA-BH-A0GY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyotxan

AGL

SNV

Missense_Mutation

rs762935611

c.136G>A

p.Val46Met

p.V46M

P35573

protein_coding

deleterious(0.02)

possibly_damaging(0.454)

TCGA-4J-AA1J-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

AGL

SNV

Missense_Mutation

c.1219N>A

p.Glu407Lys

p.E407K

P35573

protein_coding

tolerated(0.45)

probably_damaging(0.926)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

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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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