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: PYGB

Gene summary for PYGB

Gene summary.

Gene information	Species	Human
	Gene symbol	PYGB
	Gene ID	5834
	Gene name	glycogen phosphorylase B
	Gene Alias	GPBB
	Cytomap	20p11.21
	Gene Type	protein-coding
	GO ID	GO:0000272
	UniProtAcc	P11216

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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
5834	PYGB	HTA11_2487_2000001011	Human	Colorectum	SER	4.19e-05	5.17e-01	-0.1808
5834	PYGB	HTA11_1938_2000001011	Human	Colorectum	AD	5.79e-11	8.16e-01	-0.0811
5834	PYGB	HTA11_347_2000001011	Human	Colorectum	AD	2.02e-29	9.75e-01	-0.1954
5834	PYGB	HTA11_411_2000001011	Human	Colorectum	SER	9.61e-12	1.52e+00	-0.2602
5834	PYGB	HTA11_2112_2000001011	Human	Colorectum	SER	4.40e-05	8.17e-01	-0.2196
5834	PYGB	HTA11_3361_2000001011	Human	Colorectum	AD	1.90e-02	4.97e-01	-0.1207
5834	PYGB	HTA11_83_2000001011	Human	Colorectum	SER	2.24e-05	5.76e-01	-0.1526
5834	PYGB	HTA11_696_2000001011	Human	Colorectum	AD	3.22e-14	8.42e-01	-0.1464
5834	PYGB	HTA11_866_2000001011	Human	Colorectum	AD	6.89e-04	4.20e-01	-0.1001
5834	PYGB	HTA11_1391_2000001011	Human	Colorectum	AD	7.96e-08	6.77e-01	-0.059
5834	PYGB	HTA11_2992_2000001011	Human	Colorectum	SER	1.33e-02	6.84e-01	-0.1706
5834	PYGB	HTA11_5212_2000001011	Human	Colorectum	AD	1.10e-07	8.74e-01	-0.2061
5834	PYGB	HTA11_866_3004761011	Human	Colorectum	AD	5.18e-07	4.11e-01	0.096
5834	PYGB	HTA11_7696_3000711011	Human	Colorectum	AD	3.68e-04	4.52e-01	0.0674
5834	PYGB	HTA11_6818_2000001021	Human	Colorectum	AD	1.13e-12	8.25e-01	0.0588
5834	PYGB	HTA11_99999970781_79442	Human	Colorectum	MSS	3.34e-04	5.83e-01	0.294
5834	PYGB	HTA11_99999965104_69814	Human	Colorectum	MSS	6.17e-07	6.91e-01	0.281
5834	PYGB	HTA11_99999971662_82457	Human	Colorectum	MSS	9.29e-03	5.28e-01	0.3859
5834	PYGB	A002-C-010	Human	Colorectum	FAP	2.46e-03	-1.27e-01	0.242
5834	PYGB	A001-C-207	Human	Colorectum	FAP	2.08e-05	3.40e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0006091	Colorectum	AD	generation of precursor metabolites and energy	209/3918	490/18723	3.17e-28	6.61e-25	209
GO:0015980	Colorectum	AD	energy derivation by oxidation of organic compounds	143/3918	318/18723	2.78e-22	2.49e-19	143
GO:0016052	Colorectum	AD	carbohydrate catabolic process	56/3918	154/18723	7.01e-06	1.73e-04	56
GO:0044262	Colorectum	AD	cellular carbohydrate metabolic process	87/3918	283/18723	6.00e-05	1.01e-03	87
GO:00060911	Colorectum	SER	generation of precursor metabolites and energy	168/2897	490/18723	1.39e-25	1.70e-22	168
GO:00159801	Colorectum	SER	energy derivation by oxidation of organic compounds	119/2897	318/18723	5.28e-22	4.62e-19	119
GO:00160521	Colorectum	SER	carbohydrate catabolic process	38/2897	154/18723	1.92e-03	1.93e-02	38
GO:00060912	Colorectum	MSS	generation of precursor metabolites and energy	186/3467	490/18723	1.14e-24	2.15e-21	186
GO:00159802	Colorectum	MSS	energy derivation by oxidation of organic compounds	131/3467	318/18723	2.60e-21	2.70e-18	131
GO:00160522	Colorectum	MSS	carbohydrate catabolic process	45/3467	154/18723	7.93e-04	8.36e-03	45
GO:00060914	Colorectum	FAP	generation of precursor metabolites and energy	128/2622	490/18723	5.58e-13	4.28e-10	128
GO:00159804	Colorectum	FAP	energy derivation by oxidation of organic compounds	85/2622	318/18723	1.36e-09	2.77e-07	85
GO:00160523	Colorectum	FAP	carbohydrate catabolic process	44/2622	154/18723	1.82e-06	7.42e-05	44
GO:00442621	Colorectum	FAP	cellular carbohydrate metabolic process	66/2622	283/18723	1.53e-05	4.01e-04	66
GO:00160524	Colorectum	CRC	carbohydrate catabolic process	34/2078	154/18723	6.37e-05	1.39e-03	34
GO:00060915	Colorectum	CRC	generation of precursor metabolites and energy	80/2078	490/18723	2.55e-04	4.16e-03	80
GO:00442622	Colorectum	CRC	cellular carbohydrate metabolic process	49/2078	283/18723	1.06e-03	1.24e-02	49
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04922	Colorectum	AD	Glucagon signaling pathway	41/2092	107/8465	1.18e-03	7.75e-03	4.94e-03	41
hsa049221	Colorectum	AD	Glucagon signaling pathway	41/2092	107/8465	1.18e-03	7.75e-03	4.94e-03	41
hsa049222	Colorectum	SER	Glucagon signaling pathway	38/1580	107/8465	2.57e-05	3.28e-04	2.38e-04	38
hsa04217	Colorectum	SER	Necroptosis	47/1580	159/8465	5.21e-04	4.44e-03	3.22e-03	47
hsa049223	Colorectum	SER	Glucagon signaling pathway	38/1580	107/8465	2.57e-05	3.28e-04	2.38e-04	38
hsa042171	Colorectum	SER	Necroptosis	47/1580	159/8465	5.21e-04	4.44e-03	3.22e-03	47
hsa049224	Colorectum	MSS	Glucagon signaling pathway	39/1875	107/8465	5.00e-04	3.45e-03	2.11e-03	39
hsa04931	Colorectum	MSS	Insulin resistance	36/1875	108/8465	4.74e-03	2.01e-02	1.23e-02	36
hsa04910	Colorectum	MSS	Insulin signaling pathway	43/1875	137/8465	7.37e-03	2.84e-02	1.74e-02	43
hsa049225	Colorectum	MSS	Glucagon signaling pathway	39/1875	107/8465	5.00e-04	3.45e-03	2.11e-03	39
hsa049311	Colorectum	MSS	Insulin resistance	36/1875	108/8465	4.74e-03	2.01e-02	1.23e-02	36
hsa049101	Colorectum	MSS	Insulin signaling pathway	43/1875	137/8465	7.37e-03	2.84e-02	1.74e-02	43
hsa049226	Colorectum	FAP	Glucagon signaling pathway	32/1404	107/8465	4.08e-04	3.10e-03	1.89e-03	32
hsa049312	Colorectum	FAP	Insulin resistance	32/1404	108/8465	4.90e-04	3.56e-03	2.16e-03	32
hsa049102	Colorectum	FAP	Insulin signaling pathway	36/1404	137/8465	2.51e-03	1.18e-02	7.18e-03	36
hsa049227	Colorectum	FAP	Glucagon signaling pathway	32/1404	107/8465	4.08e-04	3.10e-03	1.89e-03	32
hsa049313	Colorectum	FAP	Insulin resistance	32/1404	108/8465	4.90e-04	3.56e-03	2.16e-03	32
hsa049103	Colorectum	FAP	Insulin signaling pathway	36/1404	137/8465	2.51e-03	1.18e-02	7.18e-03	36
hsa049314	Colorectum	CRC	Insulin resistance	28/1091	108/8465	1.78e-04	2.37e-03	1.61e-03	28
hsa049104	Colorectum	CRC	Insulin signaling pathway	31/1091	137/8465	1.07e-03	8.91e-03	6.03e-03	31

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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

PYGB

SNV

Missense_Mutation

novel

c.1754T>A

p.Val585Asp

p.V585D

P11216

protein_coding

deleterious(0)

possibly_damaging(0.494)

TCGA-C8-A12P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PYGB

SNV

Missense_Mutation

rs769655708

c.281G>A

p.Arg94His

p.R94H

P11216

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

PYGB

SNV

Missense_Mutation

rs767929147

c.444G>A

p.Met148Ile

p.M148I

P11216

protein_coding

deleterious(0.04)

benign(0.251)

TCGA-EW-A1OY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PYGB

SNV

Missense_Mutation

novel

c.2168A>G

p.Asp723Gly

p.D723G

P11216

protein_coding

tolerated(0.06)

benign(0.03)

TCGA-LD-A66U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PYGB

SNV

Missense_Mutation

novel

c.1229N>T

p.Arg410Leu

p.R410L

P11216

protein_coding

tolerated(0.08)

benign(0.009)

TCGA-UL-AAZ6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

herceptin

PYGB

deletion

Frame_Shift_Del

novel

c.1554delN

p.Gln518HisfsTer2

p.Q518Hfs*2

P11216

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PYGB

deletion

Frame_Shift_Del

novel

c.697delN

p.Gly233AlafsTer62

p.G233Afs*62

P11216

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

PYGB

SNV

Missense_Mutation

rs769655708

c.281N>A

p.Arg94His

p.R94H

P11216

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PYGB

SNV

Missense_Mutation

rs532747607

c.715N>A

p.Val239Ile

p.V239I

P11216

protein_coding

deleterious(0.05)

possibly_damaging(0.646)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PYGB

SNV

Missense_Mutation

novel

c.904N>A

p.Ala302Thr

p.A302T

P11216

protein_coding

deleterious(0.02)

possibly_damaging(0.881)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

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
5834	PYGB	DRUGGABLE GENOME, ENZYME		PSN357

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