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: PPP1R13B

Gene summary for PPP1R13B

Gene summary.

Gene information	Species	Human
	Gene symbol	PPP1R13B
	Gene ID	23368
	Gene name	protein phosphatase 1 regulatory subunit 13B
	Gene Alias	ASPP1
	Cytomap	14q32.33
	Gene Type	protein-coding
	GO ID	GO:0006915
	UniProtAcc	Q96KQ4

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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
23368	PPP1R13B	CCI_1	Human	Cervix	CC	1.68e-14	9.58e-01	0.528
23368	PPP1R13B	CCI_2	Human	Cervix	CC	5.88e-16	1.17e+00	0.5249
23368	PPP1R13B	CCI_3	Human	Cervix	CC	7.40e-25	1.18e+00	0.516
23368	PPP1R13B	sample3	Human	Cervix	CC	4.94e-04	1.58e-01	0.1387
23368	PPP1R13B	T3	Human	Cervix	CC	1.91e-04	1.88e-01	0.1389
23368	PPP1R13B	HTA11_3410_2000001011	Human	Colorectum	AD	1.68e-12	-4.60e-01	0.0155
23368	PPP1R13B	HTA11_347_2000001011	Human	Colorectum	AD	1.53e-05	5.35e-01	-0.1954
23368	PPP1R13B	HTA11_3361_2000001011	Human	Colorectum	AD	7.00e-03	-3.02e-01	-0.1207
23368	PPP1R13B	HTA11_866_3004761011	Human	Colorectum	AD	1.89e-05	-4.33e-01	0.096
23368	PPP1R13B	HTA11_7696_3000711011	Human	Colorectum	AD	2.06e-05	-3.20e-01	0.0674
23368	PPP1R13B	HTA11_99999970781_79442	Human	Colorectum	MSS	4.54e-13	-4.24e-01	0.294
23368	PPP1R13B	HTA11_99999971662_82457	Human	Colorectum	MSS	1.73e-18	-5.39e-01	0.3859
23368	PPP1R13B	HTA11_99999973899_84307	Human	Colorectum	MSS	2.67e-06	-3.97e-01	0.2585
23368	PPP1R13B	HTA11_99999974143_84620	Human	Colorectum	MSS	5.39e-17	-5.77e-01	0.3005
23368	PPP1R13B	F007	Human	Colorectum	FAP	2.09e-05	-4.61e-01	0.1176
23368	PPP1R13B	A002-C-010	Human	Colorectum	FAP	1.07e-05	-3.12e-01	0.242
23368	PPP1R13B	A001-C-207	Human	Colorectum	FAP	6.69e-07	-4.02e-01	0.1278
23368	PPP1R13B	A015-C-203	Human	Colorectum	FAP	2.45e-27	-4.19e-01	-0.1294
23368	PPP1R13B	A015-C-204	Human	Colorectum	FAP	1.51e-09	-4.64e-01	-0.0228
23368	PPP1R13B	A014-C-040	Human	Colorectum	FAP	1.70e-06	-4.72e-01	-0.1184

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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
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
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:009719310	Cervix	CC	intrinsic apoptotic signaling pathway	85/2311	288/18723	4.56e-15	6.46e-12	85
GO:00723329	Cervix	CC	intrinsic apoptotic signaling pathway by p53 class mediator	23/2311	76/18723	2.76e-05	4.60e-04	23
GO:007233110	Cervix	CC	signal transduction by p53 class mediator	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:007099710	Cervix	CC	neuron death	70/2311	361/18723	7.50e-05	1.03e-03	70
GO:190121610	Cervix	CC	positive regulation of neuron death	26/2311	97/18723	8.64e-05	1.15e-03	26
GO:190121410	Cervix	CC	regulation of neuron death	61/2311	319/18723	3.11e-04	3.31e-03	61
GO:00457862	Cervix	CC	negative regulation of cell cycle	67/2311	385/18723	2.21e-03	1.59e-02	67
GO:0097193	Colorectum	AD	intrinsic apoptotic signaling pathway	108/3918	288/18723	6.25e-11	6.41e-09	108
GO:0070997	Colorectum	AD	neuron death	114/3918	361/18723	1.13e-06	3.72e-05	114
GO:0072331	Colorectum	AD	signal transduction by p53 class mediator	58/3918	163/18723	1.04e-05	2.40e-04	58
GO:1901214	Colorectum	AD	regulation of neuron death	99/3918	319/18723	1.26e-05	2.76e-04	99
GO:0072332	Colorectum	AD	intrinsic apoptotic signaling pathway by p53 class mediator	30/3918	76/18723	1.72e-04	2.33e-03	30
GO:1901216	Colorectum	AD	positive regulation of neuron death	32/3918	97/18723	3.74e-03	2.63e-02	32
GO:00971932	Colorectum	MSS	intrinsic apoptotic signaling pathway	102/3467	288/18723	6.06e-12	9.82e-10	102
GO:00709972	Colorectum	MSS	neuron death	97/3467	361/18723	5.21e-05	9.31e-04	97
GO:00723312	Colorectum	MSS	signal transduction by p53 class mediator	49/3467	163/18723	2.30e-04	3.19e-03	49
GO:00723322	Colorectum	MSS	intrinsic apoptotic signaling pathway by p53 class mediator	27/3467	76/18723	3.31e-04	4.24e-03	27
GO:19012142	Colorectum	MSS	regulation of neuron death	83/3467	319/18723	5.28e-04	5.99e-03	83
GO:19012161	Colorectum	MSS	positive regulation of neuron death	30/3467	97/18723	2.15e-03	1.80e-02	30
GO:00709974	Colorectum	FAP	neuron death	81/2622	361/18723	8.35e-06	2.46e-04	81

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

PPP1R13B

SNV

Missense_Mutation

c.365C>A

p.Pro122Gln

p.P122Q

Q96KQ4

protein_coding

tolerated(0.09)

possibly_damaging(0.453)

TCGA-A2-A0EM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

PPP1R13B

SNV

Missense_Mutation

c.10A>T

p.Met4Leu

p.M4L

Q96KQ4

protein_coding

tolerated(0.09)

benign(0.222)

TCGA-A7-A26H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

PPP1R13B

SNV

Missense_Mutation

novel

c.2557N>G

p.Leu853Val

p.L853V

Q96KQ4

protein_coding

tolerated(0.62)

benign(0)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP1R13B

SNV

Missense_Mutation

c.1682N>T

p.Gly561Val

p.G561V

Q96KQ4

protein_coding

tolerated(0.07)

possibly_damaging(0.711)

TCGA-AR-A24Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PPP1R13B

SNV

Missense_Mutation

c.2102C>T

p.Ala701Val

p.A701V

Q96KQ4

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-BH-A0H3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PPP1R13B

insertion

Frame_Shift_Ins

novel

c.2931_2932insATTAAACAGTCACAAGTCATTTATTC

p.Ala978IlefsTer17

p.A978Ifs*17

Q96KQ4

protein_coding

TCGA-A8-A08T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PPP1R13B

insertion

Frame_Shift_Ins

novel

c.620_621insTGACAATGAGACCCTGTCTCAAAAAAAAATAAAAAGATCTCTTG

p.Gly208AspfsTer22

p.G208Dfs*22

Q96KQ4

protein_coding

TCGA-A8-A09C-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP1R13B

insertion

Frame_Shift_Ins

novel

c.2708_2709insATGTGCCCAAAAACCTGCTG

p.Val904CysfsTer41

p.V904Cfs*41

Q96KQ4

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP1R13B

deletion

Frame_Shift_Del

novel

c.2540delN

p.Gln847ArgfsTer24

p.Q847Rfs*24

Q96KQ4

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PPP1R13B

SNV

Missense_Mutation

rs768657019

c.3071N>T

p.Ala1024Val

p.A1024V

Q96KQ4

protein_coding

tolerated(1)

benign(0)

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

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