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: PELI2

Gene summary for PELI2

Gene summary.

Gene information	Species	Human
	Gene symbol	PELI2
	Gene ID	57161
	Gene name	pellino E3 ubiquitin protein ligase family member 2
	Gene Alias	PELI2
	Cytomap	14q22.3
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q9H716

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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
57161	PELI2	CCI_1	Human	Cervix	CC	1.63e-13	9.06e-01	0.528
57161	PELI2	CCI_2	Human	Cervix	CC	3.07e-08	1.17e+00	0.5249
57161	PELI2	CCI_3	Human	Cervix	CC	9.89e-06	4.16e-01	0.516
57161	PELI2	AEH-subject1	Human	Endometrium	AEH	5.13e-04	2.41e-01	-0.3059
57161	PELI2	AEH-subject4	Human	Endometrium	AEH	5.31e-08	3.99e-01	-0.2657
57161	PELI2	AEH-subject5	Human	Endometrium	AEH	3.09e-15	5.81e-01	-0.2953
57161	PELI2	EEC-subject1	Human	Endometrium	EEC	2.08e-02	2.58e-01	-0.2682
57161	PELI2	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	3.29e-02	-7.54e-02	-0.1934
57161	PELI2	LZE24T	Human	Esophagus	ESCC	3.33e-16	4.30e-01	0.0596
57161	PELI2	P2T-E	Human	Esophagus	ESCC	1.83e-08	1.79e-01	0.1177
57161	PELI2	P8T-E	Human	Esophagus	ESCC	6.82e-11	2.10e-01	0.0889
57161	PELI2	P9T-E	Human	Esophagus	ESCC	1.86e-06	1.91e-01	0.1131
57161	PELI2	P10T-E	Human	Esophagus	ESCC	6.02e-25	3.86e-01	0.116
57161	PELI2	P12T-E	Human	Esophagus	ESCC	4.80e-26	5.43e-01	0.1122
57161	PELI2	P15T-E	Human	Esophagus	ESCC	2.02e-29	6.55e-01	0.1149
57161	PELI2	P16T-E	Human	Esophagus	ESCC	4.46e-05	1.31e-01	0.1153
57161	PELI2	P22T-E	Human	Esophagus	ESCC	1.39e-09	9.72e-02	0.1236
57161	PELI2	P23T-E	Human	Esophagus	ESCC	2.30e-04	1.35e-01	0.108
57161	PELI2	P26T-E	Human	Esophagus	ESCC	1.21e-44	6.73e-01	0.1276
57161	PELI2	P27T-E	Human	Esophagus	ESCC	1.09e-12	1.63e-01	0.1055

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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
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
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:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:00434104	Cervix	CC	positive regulation of MAPK cascade	90/2311	480/18723	2.92e-05	4.83e-04	90
GO:00431228	Cervix	CC	regulation of I-kappaB kinase/NF-kappaB signaling	53/2311	249/18723	4.50e-05	6.87e-04	53
GO:00072497	Cervix	CC	I-kappaB kinase/NF-kappaB signaling	56/2311	281/18723	1.81e-04	2.12e-03	56
GO:00431237	Cervix	CC	positive regulation of I-kappaB kinase/NF-kappaB signaling	37/2311	186/18723	2.15e-03	1.55e-02	37
GO:00431229	Endometrium	AEH	regulation of I-kappaB kinase/NF-kappaB signaling	52/2100	249/18723	6.58e-06	1.59e-04	52
GO:00431238	Endometrium	AEH	positive regulation of I-kappaB kinase/NF-kappaB signaling	41/2100	186/18723	1.59e-05	3.32e-04	41
GO:00434105	Endometrium	AEH	positive regulation of MAPK cascade	84/2100	480/18723	2.19e-05	4.25e-04	84
GO:00072498	Endometrium	AEH	I-kappaB kinase/NF-kappaB signaling	55/2100	281/18723	2.60e-05	4.88e-04	55
GO:00002098	Endometrium	AEH	protein polyubiquitination	44/2100	236/18723	4.83e-04	4.97e-03	44
GO:004341011	Endometrium	EEC	positive regulation of MAPK cascade	89/2168	480/18723	4.21e-06	1.08e-04	89
GO:004312216	Endometrium	EEC	regulation of I-kappaB kinase/NF-kappaB signaling	53/2168	249/18723	7.59e-06	1.73e-04	53
GO:004312314	Endometrium	EEC	positive regulation of I-kappaB kinase/NF-kappaB signaling	42/2168	186/18723	1.47e-05	2.87e-04	42
GO:000724915	Endometrium	EEC	I-kappaB kinase/NF-kappaB signaling	57/2168	281/18723	1.60e-05	3.12e-04	57
GO:000020913	Endometrium	EEC	protein polyubiquitination	46/2168	236/18723	2.65e-04	3.04e-03	46
GO:000020917	Esophagus	ESCC	protein polyubiquitination	170/8552	236/18723	1.40e-16	1.09e-14	170
GO:004312318	Esophagus	ESCC	positive regulation of I-kappaB kinase/NF-kappaB signaling	132/8552	186/18723	2.07e-12	8.58e-11	132
GO:0043122110	Esophagus	ESCC	regulation of I-kappaB kinase/NF-kappaB signaling	167/8552	249/18723	6.11e-12	2.32e-10	167
GO:000724919	Esophagus	ESCC	I-kappaB kinase/NF-kappaB signaling	183/8552	281/18723	3.02e-11	1.01e-09	183
GO:00072495	Lung	IAC	I-kappaB kinase/NF-kappaB signaling	56/2061	281/18723	7.39e-06	2.62e-04	56

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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

PELI2

SNV

Missense_Mutation

rs749388627

c.686N>A

p.Arg229Gln

p.R229Q

Q9HAT8

protein_coding

deleterious(0.05)

possibly_damaging(0.582)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

PELI2

SNV

Missense_Mutation

novel

c.416T>A

p.Phe139Tyr

p.F139Y

Q9HAT8

protein_coding

tolerated(0.39)

benign(0.019)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PELI2

SNV

Missense_Mutation

rs200311934

c.974G>A

p.Arg325Gln

p.R325Q

Q9HAT8

protein_coding

tolerated(0.24)

possibly_damaging(0.598)

TCGA-A8-A09Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

PELI2

SNV

Missense_Mutation

c.801N>C

p.Gln267His

p.Q267H

Q9HAT8

protein_coding

tolerated(0.51)

possibly_damaging(0.77)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PELI2

SNV

Missense_Mutation

c.841C>T

p.Arg281Trp

p.R281W

Q9HAT8

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AR-A24S-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

PELI2

SNV

Missense_Mutation

rs557894615

c.601N>A

p.Glu201Lys

p.E201K

Q9HAT8

protein_coding

tolerated(0.44)

benign(0.146)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PELI2

insertion

Frame_Shift_Ins

novel

c.978_979insATCTTCAAATATTTTTTTGCTTGTTCTGAGAGGAAAGAATCTTGGA

p.Asp327IlefsTer41

p.D327Ifs*41

Q9HAT8

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

PELI2

SNV

Missense_Mutation

novel

c.1187C>G

p.Ala396Gly

p.A396G

Q9HAT8

protein_coding

deleterious(0.01)

probably_damaging(0.994)

TCGA-C5-A8XH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PELI2

SNV

Missense_Mutation

c.275N>G

p.Glu92Gly

p.E92G

Q9HAT8

protein_coding

deleterious(0.02)

probably_damaging(0.922)

TCGA-EA-A3HQ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PELI2

SNV

Missense_Mutation

rs375391259

c.616N>A

p.Gly206Arg

p.G206R

Q9HAT8

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-JW-A852-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

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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