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: ALG2

Gene summary for ALG2

Gene summary.

Gene information	Species	Human
	Gene symbol	ALG2
	Gene ID	85365
	Gene name	ALG2 alpha-1,3/1,6-mannosyltransferase
	Gene Alias	CDG1I
	Cytomap	9q22.33
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	A0A024R184

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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
85365	ALG2	LZE4T	Human	Esophagus	ESCC	4.16e-12	2.56e-01	0.0811
85365	ALG2	LZE7T	Human	Esophagus	ESCC	1.79e-05	1.51e-01	0.0667
85365	ALG2	LZE20T	Human	Esophagus	ESCC	2.79e-02	2.65e-02	0.0662
85365	ALG2	LZE24T	Human	Esophagus	ESCC	4.63e-18	4.35e-01	0.0596
85365	ALG2	P1T-E	Human	Esophagus	ESCC	6.32e-06	3.64e-01	0.0875
85365	ALG2	P2T-E	Human	Esophagus	ESCC	4.32e-18	3.82e-01	0.1177
85365	ALG2	P4T-E	Human	Esophagus	ESCC	1.89e-19	4.29e-01	0.1323
85365	ALG2	P5T-E	Human	Esophagus	ESCC	1.13e-03	8.16e-02	0.1327
85365	ALG2	P8T-E	Human	Esophagus	ESCC	5.44e-22	2.80e-01	0.0889
85365	ALG2	P9T-E	Human	Esophagus	ESCC	6.87e-15	3.03e-01	0.1131
85365	ALG2	P10T-E	Human	Esophagus	ESCC	2.69e-12	3.28e-01	0.116
85365	ALG2	P11T-E	Human	Esophagus	ESCC	2.01e-18	6.62e-01	0.1426
85365	ALG2	P12T-E	Human	Esophagus	ESCC	2.41e-21	3.48e-01	0.1122
85365	ALG2	P15T-E	Human	Esophagus	ESCC	4.87e-17	2.80e-01	0.1149
85365	ALG2	P16T-E	Human	Esophagus	ESCC	2.57e-16	2.08e-01	0.1153
85365	ALG2	P17T-E	Human	Esophagus	ESCC	5.17e-09	3.00e-01	0.1278
85365	ALG2	P19T-E	Human	Esophagus	ESCC	1.72e-08	5.33e-01	0.1662
85365	ALG2	P21T-E	Human	Esophagus	ESCC	2.61e-24	6.10e-01	0.1617
85365	ALG2	P22T-E	Human	Esophagus	ESCC	5.07e-19	3.09e-01	0.1236
85365	ALG2	P23T-E	Human	Esophagus	ESCC	1.99e-14	4.45e-01	0.108

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:000648714	Esophagus	ESCC	protein N-linked glycosylation	51/8552	65/18723	6.41e-08	1.13e-06	51
GO:00091002	Esophagus	ESCC	glycoprotein metabolic process	226/8552	387/18723	2.64e-07	3.94e-06	226
GO:00700854	Esophagus	ESCC	glycosylation	144/8552	240/18723	5.12e-06	5.38e-05	144
GO:00064865	Esophagus	ESCC	protein glycosylation	135/8552	226/18723	1.36e-05	1.24e-04	135
GO:00434135	Esophagus	ESCC	macromolecule glycosylation	135/8552	226/18723	1.36e-05	1.24e-04	135
GO:00091012	Esophagus	ESCC	glycoprotein biosynthetic process	181/8552	317/18723	2.54e-05	2.15e-04	181
GO:001003827	Esophagus	ESCC	response to metal ion	208/8552	373/18723	5.02e-05	3.90e-04	208
GO:00064882	Esophagus	ESCC	dolichol-linked oligosaccharide biosynthetic process	14/8552	18/18723	5.77e-03	2.14e-02	14
GO:00064902	Esophagus	ESCC	oligosaccharide-lipid intermediate biosynthetic process	14/8552	19/18723	1.27e-02	4.21e-02	14
GO:001003812	Liver	Cirrhotic	response to metal ion	150/4634	373/18723	2.27e-11	1.37e-09	150
GO:005159211	Liver	Cirrhotic	response to calcium ion	61/4634	149/18723	9.47e-06	1.38e-04	61
GO:00064873	Liver	Cirrhotic	protein N-linked glycosylation	30/4634	65/18723	1.40e-04	1.36e-03	30
GO:001003822	Liver	HCC	response to metal ion	208/7958	373/18723	1.35e-07	2.56e-06	208
GO:000648711	Liver	HCC	protein N-linked glycosylation	48/7958	65/18723	2.85e-07	5.00e-06	48
GO:00064862	Liver	HCC	protein glycosylation	122/7958	226/18723	3.11e-04	2.21e-03	122
GO:00434132	Liver	HCC	macromolecule glycosylation	122/7958	226/18723	3.11e-04	2.21e-03	122
GO:00700852	Liver	HCC	glycosylation	128/7958	240/18723	4.35e-04	2.92e-03	128
GO:0009100	Liver	HCC	glycoprotein metabolic process	193/7958	387/18723	1.89e-03	9.62e-03	193
GO:005159221	Liver	HCC	response to calcium ion	81/7958	149/18723	2.26e-03	1.13e-02	81
GO:00064875	Oral cavity	OSCC	protein N-linked glycosylation	44/7305	65/18723	2.63e-06	3.26e-05	44

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0051023	Esophagus	ESCC	N-Glycan biosynthesis	39/4205	53/8465	3.26e-04	1.15e-03	5.89e-04	39
hsa005136	Esophagus	ESCC	Various types of N-glycan biosynthesis	31/4205	42/8465	1.23e-03	3.78e-03	1.93e-03	31
hsa0051033	Esophagus	ESCC	N-Glycan biosynthesis	39/4205	53/8465	3.26e-04	1.15e-03	5.89e-04	39
hsa0051313	Esophagus	ESCC	Various types of N-glycan biosynthesis	31/4205	42/8465	1.23e-03	3.78e-03	1.93e-03	31
hsa005104	Liver	Cirrhotic	N-Glycan biosynthesis	32/2530	53/8465	3.82e-06	4.10e-05	2.53e-05	32
hsa005134	Liver	Cirrhotic	Various types of N-glycan biosynthesis	26/2530	42/8465	1.65e-05	1.41e-04	8.69e-05	26
hsa0051011	Liver	Cirrhotic	N-Glycan biosynthesis	32/2530	53/8465	3.82e-06	4.10e-05	2.53e-05	32
hsa0051311	Liver	Cirrhotic	Various types of N-glycan biosynthesis	26/2530	42/8465	1.65e-05	1.41e-04	8.69e-05	26
hsa0051021	Liver	HCC	N-Glycan biosynthesis	40/4020	53/8465	2.95e-05	1.87e-04	1.04e-04	40
hsa005132	Liver	HCC	Various types of N-glycan biosynthesis	30/4020	42/8465	1.41e-03	5.07e-03	2.82e-03	30
hsa0051031	Liver	HCC	N-Glycan biosynthesis	40/4020	53/8465	2.95e-05	1.87e-04	1.04e-04	40
hsa005133	Liver	HCC	Various types of N-glycan biosynthesis	30/4020	42/8465	1.41e-03	5.07e-03	2.82e-03	30
hsa005105	Oral cavity	OSCC	N-Glycan biosynthesis	39/3704	53/8465	9.77e-06	4.36e-05	2.22e-05	39
hsa005135	Oral cavity	OSCC	Various types of N-glycan biosynthesis	29/3704	42/8465	8.03e-04	2.32e-03	1.18e-03	29
hsa0051012	Oral cavity	OSCC	N-Glycan biosynthesis	39/3704	53/8465	9.77e-06	4.36e-05	2.22e-05	39
hsa0051312	Oral cavity	OSCC	Various types of N-glycan biosynthesis	29/3704	42/8465	8.03e-04	2.32e-03	1.18e-03	29
hsa0051022	Oral cavity	LP	N-Glycan biosynthesis	31/2418	53/8465	4.86e-06	4.14e-05	2.67e-05	31
hsa0051321	Oral cavity	LP	Various types of N-glycan biosynthesis	22/2418	42/8465	9.58e-04	4.49e-03	2.90e-03	22
hsa0051032	Oral cavity	LP	N-Glycan biosynthesis	31/2418	53/8465	4.86e-06	4.14e-05	2.67e-05	31
hsa0051331	Oral cavity	LP	Various types of N-glycan biosynthesis	22/2418	42/8465	9.58e-04	4.49e-03	2.90e-03	22

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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

ALG2

SNV

Missense_Mutation

c.1138C>T

p.Pro380Ser

p.P380S

Q9H553

protein_coding

tolerated(0.09)

possibly_damaging(0.793)

TCGA-AN-A0AL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ALG2

SNV

Missense_Mutation

c.852N>T

p.Leu284Phe

p.L284F

Q9H553

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0W7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

ALG2

insertion

Nonsense_Mutation

novel

c.806_807insCCTATATGATTTTGTGTAAAT

p.Gly269_Tyr270insLeuTyrAspPheValTerIle

p.G269_Y270insLYDFV*I

Q9H553

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ALG2

SNV

Missense_Mutation

novel

c.977N>T

p.His326Leu

p.H326L

Q9H553

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3973-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Targeted Molecular therapy

bevacizumab

ALG2

SNV

Missense_Mutation

c.905C>A

p.Ser302Tyr

p.S302Y

Q9H553

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

ALG2

SNV

Missense_Mutation

c.676T>A

p.Phe226Ile

p.F226I

Q9H553

protein_coding

tolerated(0.35)

benign(0.015)

TCGA-G4-6588-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

ALG2

SNV

Missense_Mutation

c.844C>G

p.Gln282Glu

p.Q282E

Q9H553

protein_coding

tolerated(1)

benign(0.003)

TCGA-QG-A5YV-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

xeloda

ALG2

SNV

Missense_Mutation

novel

c.569N>A

p.Ser190Tyr

p.S190Y

Q9H553

protein_coding

tolerated(0.07)

possibly_damaging(0.853)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

ALG2

SNV

Missense_Mutation

novel

c.1220N>C

p.Leu407Pro

p.L407P

Q9H553

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

ALG2

SNV

Missense_Mutation

c.1015N>C

p.Cys339Arg

p.C339R

Q9H553

protein_coding

tolerated(0.79)

benign(0.006)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

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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