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: GYS1

Gene summary for GYS1

Gene summary.

Gene information	Species	Human
	Gene symbol	GYS1
	Gene ID	2997
	Gene name	glycogen synthase 1
	Gene Alias	GSY
	Cytomap	19q13.33
	Gene Type	protein-coding
	GO ID	GO:0000271
	UniProtAcc	P13807

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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
2997	GYS1	LZE4T	Human	Esophagus	ESCC	3.18e-07	2.29e-01	0.0811
2997	GYS1	LZE7T	Human	Esophagus	ESCC	9.09e-03	1.44e-01	0.0667
2997	GYS1	LZE8T	Human	Esophagus	ESCC	8.81e-03	1.46e-01	0.067
2997	GYS1	LZE24T	Human	Esophagus	ESCC	3.53e-03	1.59e-01	0.0596
2997	GYS1	P1T-E	Human	Esophagus	ESCC	4.88e-08	3.49e-01	0.0875
2997	GYS1	P2T-E	Human	Esophagus	ESCC	1.15e-15	1.67e-01	0.1177
2997	GYS1	P4T-E	Human	Esophagus	ESCC	3.77e-13	2.89e-01	0.1323
2997	GYS1	P5T-E	Human	Esophagus	ESCC	5.44e-07	1.27e-01	0.1327
2997	GYS1	P8T-E	Human	Esophagus	ESCC	2.62e-18	3.76e-01	0.0889
2997	GYS1	P9T-E	Human	Esophagus	ESCC	1.17e-02	5.46e-02	0.1131
2997	GYS1	P10T-E	Human	Esophagus	ESCC	1.59e-14	2.47e-01	0.116
2997	GYS1	P11T-E	Human	Esophagus	ESCC	8.47e-07	3.17e-01	0.1426
2997	GYS1	P12T-E	Human	Esophagus	ESCC	3.41e-16	1.41e-01	0.1122
2997	GYS1	P15T-E	Human	Esophagus	ESCC	4.18e-15	2.98e-01	0.1149
2997	GYS1	P16T-E	Human	Esophagus	ESCC	2.98e-07	1.36e-01	0.1153
2997	GYS1	P17T-E	Human	Esophagus	ESCC	4.38e-07	2.67e-01	0.1278
2997	GYS1	P20T-E	Human	Esophagus	ESCC	1.56e-07	1.45e-01	0.1124
2997	GYS1	P21T-E	Human	Esophagus	ESCC	4.73e-23	3.02e-01	0.1617
2997	GYS1	P22T-E	Human	Esophagus	ESCC	3.90e-14	2.96e-01	0.1236
2997	GYS1	P23T-E	Human	Esophagus	ESCC	1.19e-08	1.53e-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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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: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
GO:00442626	Esophagus	ESCC	cellular carbohydrate metabolic process	160/8552	283/18723	1.43e-04	9.66e-04	160
GO:00160514	Esophagus	ESCC	carbohydrate biosynthetic process	117/8552	202/18723	2.96e-04	1.79e-03	117
GO:00346372	Esophagus	ESCC	cellular carbohydrate biosynthetic process	46/8552	78/18723	1.24e-02	4.13e-02	46
GO:000609118	Oral cavity	OSCC	generation of precursor metabolites and energy	286/7305	490/18723	1.45e-18	1.71e-16	286
GO:001598018	Oral cavity	OSCC	energy derivation by oxidation of organic compounds	190/7305	318/18723	4.10e-14	2.26e-12	190
GO:00160513	Oral cavity	OSCC	carbohydrate biosynthetic process	97/7305	202/18723	5.50e-03	2.13e-02	97
GO:00442625	Oral cavity	OSCC	cellular carbohydrate metabolic process	130/7305	283/18723	9.98e-03	3.49e-02	130
GO:000609119	Oral cavity	LP	generation of precursor metabolites and energy	214/4623	490/18723	1.12e-20	2.60e-18	214
GO:001598019	Oral cavity	LP	energy derivation by oxidation of organic compounds	145/4623	318/18723	2.44e-16	3.64e-14	145
GO:000609125	Oral cavity	EOLP	generation of precursor metabolites and energy	79/2218	490/18723	2.65e-03	1.59e-02	79
GO:001598025	Oral cavity	EOLP	energy derivation by oxidation of organic compounds	54/2218	318/18723	4.02e-03	2.23e-02	54

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05415211	Esophagus	ESCC	Diabetic cardiomyopathy	146/4205	203/8465	5.81e-11	7.78e-10	3.99e-10	146
hsa0415210	Esophagus	ESCC	AMPK signaling pathway	80/4205	121/8465	1.73e-04	6.67e-04	3.42e-04	80
hsa049109	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa049318	Esophagus	ESCC	Insulin resistance	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa041517	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0492214	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa0541538	Esophagus	ESCC	Diabetic cardiomyopathy	146/4205	203/8465	5.81e-11	7.78e-10	3.99e-10	146
hsa0415213	Esophagus	ESCC	AMPK signaling pathway	80/4205	121/8465	1.73e-04	6.67e-04	3.42e-04	80
hsa0491014	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0493113	Esophagus	ESCC	Insulin resistance	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0415114	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0492215	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa0541529	Oral cavity	OSCC	Diabetic cardiomyopathy	131/3704	203/8465	1.33e-09	1.49e-08	7.57e-09	131
hsa049108	Oral cavity	OSCC	Insulin signaling pathway	83/3704	137/8465	4.83e-05	2.00e-04	1.02e-04	83
hsa041516	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa041529	Oral cavity	OSCC	AMPK signaling pathway	71/3704	121/8465	6.29e-04	1.86e-03	9.49e-04	71
hsa049317	Oral cavity	OSCC	Insulin resistance	60/3704	108/8465	8.66e-03	1.97e-02	1.00e-02	60
hsa05415113	Oral cavity	OSCC	Diabetic cardiomyopathy	131/3704	203/8465	1.33e-09	1.49e-08	7.57e-09	131
hsa0491013	Oral cavity	OSCC	Insulin signaling pathway	83/3704	137/8465	4.83e-05	2.00e-04	1.02e-04	83
hsa0415113	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185

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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

GYS1

SNV

Missense_Mutation

c.419G>A

p.Gly140Glu

p.G140E

P13807

protein_coding

tolerated(0.15)

probably_damaging(0.968)

TCGA-A2-A0CK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

GYS1

SNV

Missense_Mutation

c.1296N>G

p.Ile432Met

p.I432M

P13807

protein_coding

tolerated(0.11)

possibly_damaging(0.815)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GYS1

SNV

Missense_Mutation

rs774914573

c.1385N>A

p.Arg462Gln

p.R462Q

P13807

protein_coding

deleterious(0.05)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GYS1

SNV

Missense_Mutation

novel

c.437G>A

p.Arg146His

p.R146H

P13807

protein_coding

tolerated(0.46)

probably_damaging(0.956)

TCGA-B6-A3ZX-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

GYS1

SNV

Missense_Mutation

rs560070875

c.575N>A

p.Arg192His

p.R192H

P13807

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0B9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

GYS1

SNV

Missense_Mutation

c.451N>A

p.Ala151Thr

p.A151T

P13807

protein_coding

tolerated(0.27)

possibly_damaging(0.558)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GYS1

SNV

Missense_Mutation

c.2090C>T

p.Ala697Val

p.A697V

P13807

protein_coding

tolerated_low_confidence(0.38)

benign(0.007)

TCGA-BH-A0HL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

GYS1

SNV

Missense_Mutation

rs781563966

c.178N>A

p.Asp60Asn

p.D60N

P13807

protein_coding

deleterious(0.05)

possibly_damaging(0.815)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

GYS1

insertion

Nonsense_Mutation

novel

c.588_589insGGCAACATGGTGAAACCCCATCTCTACAAAAAATACAAAAATTAGC

p.Pro197GlyfsTer15

p.P197Gfs*15

P13807

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

GYS1

insertion

Frame_Shift_Ins

novel

c.942-1_942insCCAGGCATGGTGGCTCACACGTGTAGTCCCA

p.His315GlnfsTer29

p.H315Qfs*29

P13807

protein_coding

TCGA-A8-A08H-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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