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: PLCB1

Gene summary for PLCB1

Gene summary.

Gene information	Species	Human
	Gene symbol	PLCB1
	Gene ID	23236
	Gene name	phospholipase C beta 1
	Gene Alias	DEE12
	Cytomap	20p12.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q9NQ66

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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
23236	PLCB1	CCI_3	Human	Cervix	CC	3.51e-23	1.15e+00	0.516
23236	PLCB1	HTA11_3410_2000001011	Human	Colorectum	AD	4.27e-06	-3.11e-01	0.0155
23236	PLCB1	HTA11_2487_2000001011	Human	Colorectum	SER	7.02e-04	-4.51e-01	-0.1808
23236	PLCB1	HTA11_78_2000001011	Human	Colorectum	AD	1.07e-02	-3.80e-01	-0.1088
23236	PLCB1	HTA11_347_2000001011	Human	Colorectum	AD	1.29e-09	-4.72e-01	-0.1954
23236	PLCB1	HTA11_866_2000001011	Human	Colorectum	AD	6.44e-08	-3.34e-01	-0.1001
23236	PLCB1	HTA11_1391_2000001011	Human	Colorectum	AD	2.93e-03	-2.88e-01	-0.059
23236	PLCB1	HTA11_7862_2000001011	Human	Colorectum	AD	2.11e-02	-5.64e-01	-0.0179
23236	PLCB1	HTA11_10711_2000001011	Human	Colorectum	AD	1.98e-04	-4.91e-01	0.0338
23236	PLCB1	HTA11_7696_3000711011	Human	Colorectum	AD	2.38e-06	-4.41e-01	0.0674
23236	PLCB1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.35e-12	-5.25e-01	0.294
23236	PLCB1	HTA11_99999971662_82457	Human	Colorectum	MSS	6.60e-07	-3.80e-01	0.3859
23236	PLCB1	HTA11_99999973899_84307	Human	Colorectum	MSS	5.95e-03	-5.37e-01	0.2585
23236	PLCB1	A001-C-207	Human	Colorectum	FAP	1.11e-10	-5.25e-01	0.1278
23236	PLCB1	A015-C-203	Human	Colorectum	FAP	4.26e-15	-5.28e-01	-0.1294
23236	PLCB1	A015-C-204	Human	Colorectum	FAP	1.52e-02	-3.79e-01	-0.0228
23236	PLCB1	A002-C-201	Human	Colorectum	FAP	1.69e-10	-4.77e-01	0.0324
23236	PLCB1	A002-C-203	Human	Colorectum	FAP	3.58e-03	-3.70e-01	0.2786
23236	PLCB1	A001-C-108	Human	Colorectum	FAP	6.39e-08	-4.00e-01	-0.0272
23236	PLCB1	A002-C-021	Human	Colorectum	FAP	6.74e-03	-3.54e-01	0.1171

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:00160424	Colorectum	CRC	lipid catabolic process	53/2078	320/18723	1.89e-03	1.93e-02	53
GO:0021537	Colorectum	CRC	telencephalon development	43/2078	248/18723	2.01e-03	2.01e-02	43
GO:00308561	Colorectum	CRC	regulation of epithelial cell differentiation	29/2078	154/18723	3.02e-03	2.71e-02	29
GO:00703041	Colorectum	CRC	positive regulation of stress-activated protein kinase signaling cascade	25/2078	128/18723	3.44e-03	2.92e-02	25
GO:00991701	Colorectum	CRC	postsynaptic modulation of chemical synaptic transmission	6/2078	15/18723	3.82e-03	3.19e-02	6
GO:00031584	Colorectum	CRC	endothelium development	26/2078	136/18723	3.91e-03	3.24e-02	26
GO:0043410	Colorectum	CRC	positive regulation of MAPK cascade	72/2078	480/18723	4.85e-03	3.74e-02	72
GO:00454463	Colorectum	CRC	endothelial cell differentiation	23/2078	118/18723	5.01e-03	3.85e-02	23
GO:00328741	Colorectum	CRC	positive regulation of stress-activated MAPK cascade	24/2078	126/18723	5.68e-03	4.26e-02	24
GO:00900682	Colorectum	CRC	positive regulation of cell cycle process	39/2078	236/18723	7.23e-03	4.98e-02	39
GO:00514039	Endometrium	AEH	stress-activated MAPK cascade	50/2100	239/18723	9.33e-06	2.18e-04	50
GO:00310989	Endometrium	AEH	stress-activated protein kinase signaling cascade	51/2100	247/18723	1.12e-05	2.52e-04	51
GO:00328728	Endometrium	AEH	regulation of stress-activated MAPK cascade	42/2100	192/18723	1.53e-05	3.23e-04	42
GO:00303364	Endometrium	AEH	negative regulation of cell migration	65/2100	344/18723	1.65e-05	3.42e-04	65
GO:20001464	Endometrium	AEH	negative regulation of cell motility	67/2100	359/18723	1.86e-05	3.77e-04	67
GO:00512714	Endometrium	AEH	negative regulation of cellular component movement	68/2100	367/18723	2.06e-05	4.11e-04	68
GO:00434105	Endometrium	AEH	positive regulation of MAPK cascade	84/2100	480/18723	2.19e-05	4.25e-04	84
GO:00703028	Endometrium	AEH	regulation of stress-activated protein kinase signaling cascade	42/2100	195/18723	2.27e-05	4.35e-04	42
GO:00400134	Endometrium	AEH	negative regulation of locomotion	70/2100	391/18723	4.95e-05	8.05e-04	70
GO:000315810	Endometrium	AEH	endothelium development	31/2100	136/18723	8.53e-05	1.26e-03	31

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541520	Cervix	CC	Diabetic cardiomyopathy	76/1267	203/8465	1.40e-15	6.46e-14	3.82e-14	76
hsa0501018	Cervix	CC	Alzheimer disease	113/1267	384/8465	9.67e-14	3.92e-12	2.32e-12	113
hsa0501618	Cervix	CC	Huntington disease	94/1267	306/8465	8.49e-13	3.06e-11	1.81e-11	94
hsa0502218	Cervix	CC	Pathways of neurodegeneration - multiple diseases	128/1267	476/8465	2.87e-12	9.29e-11	5.50e-11	128
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0516318	Cervix	CC	Human cytomegalovirus infection	65/1267	225/8465	4.59e-08	6.47e-07	3.83e-07	65
hsa0513120	Cervix	CC	Shigellosis	69/1267	247/8465	7.64e-08	1.03e-06	6.10e-07	69
hsa0491520	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa0472318	Cervix	CC	Retrograde endocannabinoid signaling	42/1267	148/8465	1.79e-05	1.42e-04	8.40e-05	42
hsa043109	Cervix	CC	Wnt signaling pathway	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa051465	Cervix	CC	Amoebiasis	29/1267	102/8465	3.31e-04	1.70e-03	1.01e-03	29
hsa0491212	Cervix	CC	GnRH signaling pathway	26/1267	93/8465	8.72e-04	3.87e-03	2.29e-03	26
hsa0501716	Cervix	CC	Spinocerebellar ataxia	35/1267	143/8465	1.77e-03	7.21e-03	4.26e-03	35
hsa0492812	Cervix	CC	Parathyroid hormone synthesis, secretion and action	27/1267	106/8465	3.12e-03	1.19e-02	7.03e-03	27
hsa04062	Cervix	CC	Chemokine signaling pathway	43/1267	192/8465	3.60e-03	1.34e-02	7.91e-03	43
hsa049336	Cervix	CC	AGE-RAGE signaling pathway in diabetic complications	25/1267	100/8465	5.64e-03	1.88e-02	1.11e-02	25
hsa046213	Cervix	CC	NOD-like receptor signaling pathway	41/1267	186/8465	5.90e-03	1.95e-02	1.15e-02	41
hsa0497116	Cervix	CC	Gastric acid secretion	20/1267	76/8465	6.93e-03	2.27e-02	1.34e-02	20
hsa049265	Cervix	CC	Relaxin signaling pathway	30/1267	129/8465	7.92e-03	2.56e-02	1.51e-02	30
hsa049218	Cervix	CC	Oxytocin signaling pathway	34/1267	154/8465	1.12e-02	3.42e-02	2.02e-02	34

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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

PLCB1

SNV

Missense_Mutation

c.2245N>A

p.Val749Ile

p.V749I

Q9NQ66

protein_coding

deleterious(0.02)

possibly_damaging(0.609)

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

PLCB1

SNV

Missense_Mutation

c.2548G>A

p.Glu850Lys

p.E850K

Q9NQ66

protein_coding

tolerated(0.33)

benign(0.025)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLCB1

SNV

Missense_Mutation

c.978N>A

p.Phe326Leu

p.F326L

Q9NQ66

protein_coding

deleterious(0)

possibly_damaging(0.897)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLCB1

SNV

Missense_Mutation

rs867281730

c.1229N>T

p.Ser410Leu

p.S410L

Q9NQ66

protein_coding

deleterious(0)

possibly_damaging(0.672)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLCB1

SNV

Missense_Mutation

c.662N>A

p.Pro221His

p.P221H

Q9NQ66

protein_coding

tolerated(0.06)

possibly_damaging(0.593)

TCGA-AO-A0J2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PLCB1

SNV

Missense_Mutation

novel

c.351G>T

p.Leu117Phe

p.L117F

Q9NQ66

protein_coding

tolerated(0.15)

benign(0.385)

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLCB1

SNV

Missense_Mutation

novel

c.352A>T

p.Asn118Tyr

p.N118Y

Q9NQ66

protein_coding

deleterious(0)

possibly_damaging(0.852)

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLCB1

SNV

Missense_Mutation

novel

c.976T>C

p.Phe326Leu

p.F326L

Q9NQ66

protein_coding

deleterious(0)

possibly_damaging(0.897)

TCGA-BH-A5J0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLCB1

SNV

Missense_Mutation

c.665G>A

p.Arg222Gln

p.R222Q

Q9NQ66

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-E2-A1LK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PLCB1

SNV

Missense_Mutation

rs867281730

c.1229N>T

p.Ser410Leu

p.S410L

Q9NQ66

protein_coding

deleterious(0)

possibly_damaging(0.672)

TCGA-E2-A9RU-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

arimidex

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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
23236	PLCB1	ENZYME, DRUGGABLE GENOME, PHOSPHOLIPASE		Selective serotonin reuptake inhibitors		25649181

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