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: PIK3CB

Gene summary for PIK3CB

Gene summary.

Gene information	Species	Human
	Gene symbol	PIK3CB
	Gene ID	5291
	Gene name	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta
	Gene Alias	P110BETA
	Cytomap	3q22.3
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	B4DER4

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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
5291	PIK3CB	CCI_1	Human	Cervix	CC	1.05e-03	8.02e-01	0.528
5291	PIK3CB	CCI_2	Human	Cervix	CC	2.19e-04	6.88e-01	0.5249
5291	PIK3CB	CCI_3	Human	Cervix	CC	2.88e-07	6.84e-01	0.516
5291	PIK3CB	HTA11_3410_2000001011	Human	Colorectum	AD	3.49e-13	-5.46e-01	0.0155
5291	PIK3CB	HTA11_347_2000001011	Human	Colorectum	AD	6.10e-04	4.24e-01	-0.1954
5291	PIK3CB	HTA11_866_3004761011	Human	Colorectum	AD	1.07e-05	-4.48e-01	0.096
5291	PIK3CB	HTA11_10711_2000001011	Human	Colorectum	AD	2.25e-02	-2.67e-01	0.0338
5291	PIK3CB	HTA11_7696_3000711011	Human	Colorectum	AD	2.08e-10	-3.80e-01	0.0674
5291	PIK3CB	HTA11_99999970781_79442	Human	Colorectum	MSS	5.70e-14	-4.34e-01	0.294
5291	PIK3CB	HTA11_99999974143_84620	Human	Colorectum	MSS	1.14e-11	-4.94e-01	0.3005
5291	PIK3CB	F007	Human	Colorectum	FAP	3.57e-04	-4.16e-01	0.1176
5291	PIK3CB	A001-C-207	Human	Colorectum	FAP	3.39e-03	-1.93e-01	0.1278
5291	PIK3CB	A015-C-203	Human	Colorectum	FAP	1.45e-29	-4.98e-01	-0.1294
5291	PIK3CB	A015-C-204	Human	Colorectum	FAP	3.70e-08	-4.00e-01	-0.0228
5291	PIK3CB	A014-C-040	Human	Colorectum	FAP	4.58e-03	-3.61e-01	-0.1184
5291	PIK3CB	A002-C-201	Human	Colorectum	FAP	1.95e-16	-3.87e-01	0.0324
5291	PIK3CB	A002-C-203	Human	Colorectum	FAP	7.10e-04	-1.69e-01	0.2786
5291	PIK3CB	A001-C-119	Human	Colorectum	FAP	2.46e-08	-4.76e-01	-0.1557
5291	PIK3CB	A001-C-108	Human	Colorectum	FAP	7.35e-17	-2.93e-01	-0.0272
5291	PIK3CB	A002-C-205	Human	Colorectum	FAP	2.89e-23	-4.38e-01	-0.1236

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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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:000716031	Lung	MIAC	cell-matrix adhesion	35/967	233/18723	1.26e-08	7.17e-06	35
GO:000195231	Lung	MIAC	regulation of cell-matrix adhesion	24/967	128/18723	3.46e-08	1.37e-05	24
GO:001081032	Lung	MIAC	regulation of cell-substrate adhesion	33/967	221/18723	3.79e-08	1.39e-05	33
GO:003158931	Lung	MIAC	cell-substrate adhesion	44/967	363/18723	1.30e-07	3.56e-05	44
GO:000989632	Lung	MIAC	positive regulation of catabolic process	54/967	492/18723	1.42e-07	3.64e-05	54
GO:003133132	Lung	MIAC	positive regulation of cellular catabolic process	46/967	427/18723	2.00e-06	2.44e-04	46
GO:005105621	Lung	MIAC	regulation of small GTPase mediated signal transduction	35/967	302/18723	6.81e-06	6.35e-04	35
GO:004206023	Lung	MIAC	wound healing	41/967	422/18723	7.92e-05	3.66e-03	41
GO:000226232	Lung	MIAC	myeloid cell homeostasis	20/967	157/18723	1.74e-04	6.43e-03	20
GO:004340931	Lung	MIAC	negative regulation of MAPK cascade	21/967	180/18723	4.12e-04	1.19e-02	21
GO:00518972	Lung	MIAC	positive regulation of protein kinase B signaling	16/967	120/18723	4.51e-04	1.25e-02	16
GO:004825922	Lung	MIAC	regulation of receptor-mediated endocytosis	15/967	110/18723	5.28e-04	1.37e-02	15
GO:00518963	Lung	MIAC	regulation of protein kinase B signaling	21/967	185/18723	5.95e-04	1.49e-02	21
GO:000689822	Lung	MIAC	receptor-mediated endocytosis	25/967	244/18723	8.78e-04	1.88e-02	25
GO:004887223	Lung	MIAC	homeostasis of number of cells	27/967	272/18723	9.04e-04	1.92e-02	27
GO:003010022	Lung	MIAC	regulation of endocytosis	22/967	211/18723	1.39e-03	2.51e-02	22
GO:00434911	Lung	MIAC	protein kinase B signaling	22/967	211/18723	1.39e-03	2.51e-02	22
GO:004593632	Lung	MIAC	negative regulation of phosphate metabolic process	38/967	441/18723	1.44e-03	2.54e-02	38
GO:001056332	Lung	MIAC	negative regulation of phosphorus metabolic process	38/967	442/18723	1.50e-03	2.60e-02	38
GO:005134832	Lung	MIAC	negative regulation of transferase activity	26/967	268/18723	1.55e-03	2.65e-02	26

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517120	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa0520820	Cervix	CC	Chemical carcinogenesis - reactive oxygen species	92/1267	223/8465	4.71e-22	5.09e-20	3.01e-20	92
hsa0502018	Cervix	CC	Prion disease	98/1267	273/8465	2.64e-18	1.42e-16	8.42e-17	98
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
hsa0493218	Cervix	CC	Non-alcoholic fatty liver disease	58/1267	155/8465	3.58e-12	1.05e-10	6.23e-11	58
hsa0541820	Cervix	CC	Fluid shear stress and atherosclerosis	50/1267	139/8465	5.71e-10	1.32e-08	7.81e-09	50
hsa0513220	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0516720	Cervix	CC	Kaposi sarcoma-associated herpesvirus infection	60/1267	194/8465	9.74e-09	1.58e-07	9.33e-08	60
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
hsa0520516	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0421810	Cervix	CC	Cellular senescence	49/1267	156/8465	1.30e-07	1.63e-06	9.61e-07	49
hsa0451010	Cervix	CC	Focal adhesion	59/1267	203/8465	1.53e-07	1.84e-06	1.09e-06	59
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0491520	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa0516920	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa0516620	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa0467020	Cervix	CC	Leukocyte transendothelial migration	36/1267	114/8465	5.22e-06	4.83e-05	2.86e-05	36

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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

PIK3CB

SNV

Missense_Mutation

c.1491N>C

p.Glu497Asp

p.E497D

P42338

protein_coding

tolerated(0.18)

benign(0.02)

TCGA-A2-A0SY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

arimidex

PIK3CB

SNV

Missense_Mutation

novel

c.1933N>T

p.Val645Leu

p.V645L

P42338

protein_coding

deleterious(0.01)

probably_damaging(0.932)

TCGA-A8-A0A2-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

PIK3CB

SNV

Missense_Mutation

rs774181749

c.308N>A

p.Arg103Lys

p.R103K

P42338

protein_coding

tolerated(0.35)

benign(0.206)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PIK3CB

SNV

Missense_Mutation

c.2302N>T

p.Leu768Phe

p.L768F

P42338

protein_coding

deleterious(0.05)

benign(0.41)

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PIK3CB

SNV

Missense_Mutation

c.911T>G

p.Ile304Arg

p.I304R

P42338

protein_coding

tolerated(0.74)

benign(0.065)

TCGA-AN-A0AM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PIK3CB

SNV

Missense_Mutation

c.3040G>A

p.Glu1014Lys

p.E1014K

P42338

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AO-A0JC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

PIK3CB

SNV

Missense_Mutation

rs768628634

c.2189N>T

p.Ala730Val

p.A730V

P42338

protein_coding

tolerated(0.11)

benign(0.101)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

PIK3CB

SNV

Missense_Mutation

c.3151N>A

p.Glu1051Lys

p.E1051K

P42338

protein_coding

deleterious(0.03)

possibly_damaging(0.459)

TCGA-D8-A1JC-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

PIK3CB

SNV

Missense_Mutation

c.1658A>G

p.Asn553Ser

p.N553S

P42338

protein_coding

tolerated(0.26)

benign(0.365)

TCGA-E2-A14Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

PIK3CB

insertion

Nonsense_Mutation

novel

c.3128_3129insTTTTGTTGTCCTTCTTAATGTTCTCAGTCAAATAAATGAGTG

p.Gln1043delinsHisPheValValLeuLeuAsnValLeuSerGlnIleAsnGluTer

p.Q1043delinsHFVVLLNVLSQINE*

P42338

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

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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
5291	PIK3CB	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, KINASE, G PROTEIN COUPLED RECEPTOR	inhibitor	249565691	CHEMBL1086377
5291	PIK3CB	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, KINASE, G PROTEIN COUPLED RECEPTOR	inhibitor	BYL719	ALPELISIB
5291	PIK3CB	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, KINASE, G PROTEIN COUPLED RECEPTOR	inhibitor	BYL719	ALPELISIB
5291	PIK3CB	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, KINASE, G PROTEIN COUPLED RECEPTOR	inhibitor	CHEMBL2219421	RECILISIB
5291	PIK3CB	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, KINASE, G PROTEIN COUPLED RECEPTOR	inhibitor	249565646	PILARALISIB
5291	PIK3CB	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, KINASE, G PROTEIN COUPLED RECEPTOR	inhibitor	249565693
5291	PIK3CB	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, KINASE, G PROTEIN COUPLED RECEPTOR	inhibitor	CHEMBL2387080	TASELISIB
5291	PIK3CB	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, KINASE, G PROTEIN COUPLED RECEPTOR		SURAMIN	SURAMIN	15833899,11473364
5291	PIK3CB	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, KINASE, G PROTEIN COUPLED RECEPTOR	inhibitor	178102645
5291	PIK3CB	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE, KINASE, G PROTEIN COUPLED RECEPTOR		Buparlisib	BUPARLISIB

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