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: PHKB

Gene summary for PHKB

Gene summary.

Gene information	Species	Human
	Gene symbol	PHKB
	Gene ID	5257
	Gene name	phosphorylase kinase regulatory subunit beta
	Gene Alias	PHKB
	Cytomap	16q12.1
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	Q93100

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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
5257	PHKB	CCI_2	Human	Cervix	CC	1.60e-03	6.59e-01	0.5249
5257	PHKB	CCI_3	Human	Cervix	CC	1.47e-03	6.43e-01	0.516
5257	PHKB	HTA11_3410_2000001011	Human	Colorectum	AD	1.41e-14	-5.28e-01	0.0155
5257	PHKB	HTA11_3361_2000001011	Human	Colorectum	AD	1.65e-06	-6.32e-01	-0.1207
5257	PHKB	HTA11_696_2000001011	Human	Colorectum	AD	8.97e-04	-3.27e-01	-0.1464
5257	PHKB	HTA11_866_3004761011	Human	Colorectum	AD	2.67e-09	-5.70e-01	0.096
5257	PHKB	HTA11_10711_2000001011	Human	Colorectum	AD	1.03e-04	-5.26e-01	0.0338
5257	PHKB	HTA11_7696_3000711011	Human	Colorectum	AD	6.65e-07	-4.27e-01	0.0674
5257	PHKB	HTA11_99999970781_79442	Human	Colorectum	MSS	2.20e-07	-4.03e-01	0.294
5257	PHKB	HTA11_99999971662_82457	Human	Colorectum	MSS	3.10e-03	-3.86e-01	0.3859
5257	PHKB	HTA11_99999973899_84307	Human	Colorectum	MSS	5.89e-03	-5.32e-01	0.2585
5257	PHKB	HTA11_99999974143_84620	Human	Colorectum	MSS	1.16e-23	-6.83e-01	0.3005
5257	PHKB	F007	Human	Colorectum	FAP	1.51e-04	-3.44e-01	0.1176
5257	PHKB	A002-C-010	Human	Colorectum	FAP	2.25e-04	-2.04e-01	0.242
5257	PHKB	A001-C-207	Human	Colorectum	FAP	1.11e-04	-3.15e-01	0.1278
5257	PHKB	A015-C-203	Human	Colorectum	FAP	2.91e-33	-5.56e-01	-0.1294
5257	PHKB	A015-C-204	Human	Colorectum	FAP	8.10e-09	-4.64e-01	-0.0228
5257	PHKB	A014-C-040	Human	Colorectum	FAP	2.99e-06	-5.91e-01	-0.1184
5257	PHKB	A002-C-201	Human	Colorectum	FAP	1.12e-19	-4.96e-01	0.0324
5257	PHKB	A002-C-203	Human	Colorectum	FAP	1.32e-04	-2.24e-01	0.2786

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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
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
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
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: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: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:0044262	Colorectum	AD	cellular carbohydrate metabolic process	87/3918	283/18723	6.00e-05	1.01e-03	87
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: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:00442621	Colorectum	FAP	cellular carbohydrate metabolic process	66/2622	283/18723	1.53e-05	4.01e-04	66
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
GO:00060917	Liver	NAFLD	generation of precursor metabolites and energy	84/1882	490/18723	7.03e-07	3.95e-05	84
GO:00442623	Liver	NAFLD	cellular carbohydrate metabolic process	55/1882	283/18723	1.27e-06	6.01e-05	55
GO:0005976	Liver	NAFLD	polysaccharide metabolic process	24/1882	107/18723	1.28e-04	2.46e-03	24
GO:0044264	Liver	NAFLD	cellular polysaccharide metabolic process	22/1882	96/18723	1.73e-04	3.08e-03	22
GO:0005977	Liver	NAFLD	glycogen metabolic process	18/1882	72/18723	2.09e-04	3.60e-03	18

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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
hsa049224	Colorectum	MSS	Glucagon signaling pathway	39/1875	107/8465	5.00e-04	3.45e-03	2.11e-03	39
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
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
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
hsa049103	Colorectum	FAP	Insulin signaling pathway	36/1404	137/8465	2.51e-03	1.18e-02	7.18e-03	36
hsa049104	Colorectum	CRC	Insulin signaling pathway	31/1091	137/8465	1.07e-03	8.91e-03	6.03e-03	31
hsa049228	Colorectum	CRC	Glucagon signaling pathway	24/1091	107/8465	4.21e-03	2.47e-02	1.67e-02	24
hsa049105	Colorectum	CRC	Insulin signaling pathway	31/1091	137/8465	1.07e-03	8.91e-03	6.03e-03	31
hsa049229	Colorectum	CRC	Glucagon signaling pathway	24/1091	107/8465	4.21e-03	2.47e-02	1.67e-02	24
hsa049109	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0492214	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa0491014	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0492215	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa049106	Liver	NAFLD	Insulin signaling pathway	29/1043	137/8465	2.23e-03	2.46e-02	1.99e-02	29
hsa0492210	Liver	NAFLD	Glucagon signaling pathway	24/1043	107/8465	2.33e-03	2.46e-02	1.99e-02	24

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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

PHKB

SNV

Missense_Mutation

c.2428N>T

p.Val810Leu

p.V810L

Q93100

protein_coding

tolerated(0.5)

benign(0.139)

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

PHKB

SNV

Missense_Mutation

novel

c.2435N>C

p.Leu812Pro

p.L812P

Q93100

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-A2-A3XW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamyicin

PHKB

SNV

Missense_Mutation

c.1751N>G

p.Asp584Gly

p.D584G

Q93100

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PHKB

SNV

Missense_Mutation

novel

c.2909N>T

p.Ser970Leu

p.S970L

Q93100

protein_coding

deleterious(0)

probably_damaging(0.96)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PHKB

SNV

Missense_Mutation

c.26N>G

p.Ala9Gly

p.A9G

Q93100

protein_coding

deleterious_low_confidence(0.05)

benign(0.015)

TCGA-E2-A14S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

PHKB

insertion

Frame_Shift_Ins

novel

c.296_297insG

p.Ala100CysfsTer6

p.A100Cfs*6

Q93100

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

PHKB

insertion

In_Frame_Ins

novel

c.298_299insTTCATGTTATATATGGATGGAATT

p.Ala100delinsValHisValIleTyrGlyTrpAsnSer

p.A100delinsVHVIYGWNS

Q93100

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

PHKB

deletion

Frame_Shift_Del

c.664delG

p.Glu222LysfsTer20

p.E222Kfs*20

Q93100

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

PHKB

SNV

Missense_Mutation

c.1243N>A

p.Asp415Asn

p.D415N

Q93100

protein_coding

tolerated(0.12)

benign(0.082)

TCGA-EK-A2R7-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PHKB

SNV

Missense_Mutation

novel

c.3031N>A

p.Glu1011Lys

p.E1011K

Q93100

protein_coding

tolerated(0.12)

benign(0.358)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

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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