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: PPP1R15B

Gene summary for PPP1R15B

Gene summary.

Gene information	Species	Human
	Gene symbol	PPP1R15B
	Gene ID	84919
	Gene name	protein phosphatase 1 regulatory subunit 15B
	Gene Alias	CREP
	Cytomap	1q32.1
	Gene Type	protein-coding
	GO ID	GO:0000302
	UniProtAcc	NA

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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
84919	PPP1R15B	Adj_PTCwithHT_8	Human	Thyroid	HT	5.91e-05	-4.04e-01	0.0267
84919	PPP1R15B	PTCwithHT_6	Human	Thyroid	HT	5.26e-03	-3.61e-01	0.02
84919	PPP1R15B	PTCwithHT_8	Human	Thyroid	HT	1.28e-08	-4.04e-01	0.0351
84919	PPP1R15B	PTCwithoutHT_2	Human	Thyroid	PTC	2.76e-08	-4.04e-01	0.0419
84919	PPP1R15B	male-WTA	Human	Thyroid	PTC	2.18e-30	-1.91e-01	0.1037
84919	PPP1R15B	PTC01	Human	Thyroid	PTC	1.58e-10	-2.33e-01	0.1899
84919	PPP1R15B	PTC04	Human	Thyroid	PTC	1.37e-14	-5.29e-02	0.1927
84919	PPP1R15B	PTC05	Human	Thyroid	PTC	8.70e-06	3.23e-01	0.2065
84919	PPP1R15B	PTC06	Human	Thyroid	PTC	5.57e-15	7.22e-02	0.2057
84919	PPP1R15B	PTC07	Human	Thyroid	PTC	6.49e-11	9.98e-03	0.2044
84919	PPP1R15B	ATC09	Human	Thyroid	ATC	5.38e-03	-1.23e-01	0.2871
84919	PPP1R15B	ATC12	Human	Thyroid	ATC	5.14e-11	-2.58e-01	0.34
84919	PPP1R15B	ATC13	Human	Thyroid	ATC	1.26e-15	-3.70e-03	0.34
84919	PPP1R15B	ATC2	Human	Thyroid	ATC	1.49e-03	7.71e-01	0.34
84919	PPP1R15B	ATC4	Human	Thyroid	ATC	7.26e-13	-2.20e-01	0.34
84919	PPP1R15B	ATC5	Human	Thyroid	ATC	5.86e-12	3.95e-02	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0034976111	Esophagus	ESCC	response to endoplasmic reticulum stress	192/8552	256/18723	7.15e-22	1.30e-19	192
GO:0006979111	Esophagus	ESCC	response to oxidative stress	303/8552	446/18723	7.15e-22	1.30e-19	303
GO:0006413110	Esophagus	ESCC	translational initiation	100/8552	118/18723	1.16e-18	1.25e-16	100
GO:0035966111	Esophagus	ESCC	response to topologically incorrect protein	125/8552	159/18723	1.44e-17	1.27e-15	125
GO:0006417111	Esophagus	ESCC	regulation of translation	304/8552	468/18723	1.53e-17	1.33e-15	304
GO:0006986111	Esophagus	ESCC	response to unfolded protein	107/8552	137/18723	7.01e-15	3.87e-13	107
GO:0035967111	Esophagus	ESCC	cellular response to topologically incorrect protein	90/8552	116/18723	1.94e-12	8.11e-11	90
GO:0010563111	Esophagus	ESCC	negative regulation of phosphorus metabolic process	274/8552	442/18723	2.32e-12	9.41e-11	274
GO:0045936111	Esophagus	ESCC	negative regulation of phosphate metabolic process	273/8552	441/18723	3.18e-12	1.25e-10	273
GO:000644617	Esophagus	ESCC	regulation of translational initiation	65/8552	79/18723	2.04e-11	7.07e-10	65
GO:0000302111	Esophagus	ESCC	response to reactive oxygen species	150/8552	222/18723	3.06e-11	1.02e-09	150
GO:0042326111	Esophagus	ESCC	negative regulation of phosphorylation	237/8552	385/18723	1.86e-10	5.33e-09	237
GO:0034620111	Esophagus	ESCC	cellular response to unfolded protein	74/8552	96/18723	3.10e-10	8.66e-09	74
GO:0001933111	Esophagus	ESCC	negative regulation of protein phosphorylation	213/8552	342/18723	3.54e-10	9.76e-09	213
GO:001631110	Esophagus	ESCC	dephosphorylation	251/8552	417/18723	1.26e-09	2.99e-08	251
GO:003096818	Esophagus	ESCC	endoplasmic reticulum unfolded protein response	59/8552	74/18723	1.90e-09	4.36e-08	59
GO:0042542111	Esophagus	ESCC	response to hydrogen peroxide	102/8552	146/18723	2.64e-09	5.81e-08	102
GO:000647018	Esophagus	ESCC	protein dephosphorylation	177/8552	281/18723	3.13e-09	6.72e-08	177
GO:1905897111	Esophagus	ESCC	regulation of response to endoplasmic reticulum stress	63/8552	82/18723	8.16e-09	1.66e-07	63
GO:0035304111	Esophagus	ESCC	regulation of protein dephosphorylation	66/8552	90/18723	8.82e-08	1.48e-06	66

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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

PPP1R15B

SNV

Missense_Mutation

novel

c.1677N>A

p.Phe559Leu

p.F559L

Q5SWA1

protein_coding

tolerated(0.07)

probably_damaging(0.999)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

PPP1R15B

SNV

Missense_Mutation

c.171G>C

p.Glu57Asp

p.E57D

Q5SWA1

protein_coding

deleterious_low_confidence(0.04)

benign(0.073)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PPP1R15B

SNV

Missense_Mutation

c.1861G>A

p.Asp621Asn

p.D621N

Q5SWA1

protein_coding

tolerated(0.1)

benign(0.149)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP1R15B

SNV

Missense_Mutation

c.1341N>A

p.Asp447Glu

p.D447E

Q5SWA1

protein_coding

tolerated(0.2)

possibly_damaging(0.693)

TCGA-B6-A0IJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PPP1R15B

SNV

Missense_Mutation

c.742N>C

p.Val248Leu

p.V248L

Q5SWA1

protein_coding

deleterious(0.03)

benign(0.159)

TCGA-E9-A244-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PPP1R15B

SNV

Missense_Mutation

novel

c.1531G>C

p.Glu511Gln

p.E511Q

Q5SWA1

protein_coding

tolerated(0.3)

benign(0.177)

TCGA-LL-A5YM-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unspecific

letrozole

PPP1R15B

insertion

Frame_Shift_Ins

novel

c.1228_1229insCC

p.Glu410AlafsTer17

p.E410Afs*17

Q5SWA1

protein_coding

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP1R15B

insertion

Frame_Shift_Ins

novel

c.1226_1227insTGGCCTTCCAAAGTGCTGGGATTACAGGCGTG

p.Glu410GlyfsTer27

p.E410Gfs*27

Q5SWA1

protein_coding

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP1R15B

insertion

Frame_Shift_Ins

novel

c.1024_1025insGTCCATTGTGGCCATTTCTGAGTGTC

p.Asn342SerfsTer33

p.N342Sfs*33

Q5SWA1

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP1R15B

insertion

Frame_Shift_Ins

novel

c.181_182insTTCTTAGTTGGGAATATTCTGAAAGAATTGGTAGCATAAAGGG

p.Ser61IlefsTer95

p.S61Ifs*95

Q5SWA1

protein_coding

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

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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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