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: PELI1

Gene summary for PELI1

Gene summary.

Gene information	Species	Human
	Gene symbol	PELI1
	Gene ID	57162
	Gene name	pellino E3 ubiquitin protein ligase 1
	Gene Alias	PELI1
	Cytomap	2p14
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	Q53T26

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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
57162	PELI1	CCI_1	Human	Cervix	CC	3.13e-09	1.44e+00	0.528
57162	PELI1	CCI_3	Human	Cervix	CC	1.90e-04	6.26e-01	0.516
57162	PELI1	HTA11_3410_2000001011	Human	Colorectum	AD	3.23e-04	-2.96e-01	0.0155
57162	PELI1	HTA11_3361_2000001011	Human	Colorectum	AD	9.65e-06	-5.58e-01	-0.1207
57162	PELI1	HTA11_866_3004761011	Human	Colorectum	AD	3.92e-04	-3.60e-01	0.096
57162	PELI1	HTA11_7696_3000711011	Human	Colorectum	AD	2.19e-02	-3.68e-01	0.0674
57162	PELI1	HTA11_99999971662_82457	Human	Colorectum	MSS	1.12e-03	-3.53e-01	0.3859
57162	PELI1	HTA11_99999973899_84307	Human	Colorectum	MSS	3.61e-03	-5.20e-01	0.2585
57162	PELI1	HTA11_99999974143_84620	Human	Colorectum	MSS	6.66e-04	-3.31e-01	0.3005
57162	PELI1	A015-C-203	Human	Colorectum	FAP	1.22e-19	-3.19e-01	-0.1294
57162	PELI1	A015-C-204	Human	Colorectum	FAP	1.19e-03	-2.66e-01	-0.0228
57162	PELI1	A014-C-040	Human	Colorectum	FAP	4.99e-04	-4.51e-01	-0.1184
57162	PELI1	A002-C-201	Human	Colorectum	FAP	7.12e-13	-3.70e-01	0.0324
57162	PELI1	A001-C-119	Human	Colorectum	FAP	4.08e-08	-3.86e-01	-0.1557
57162	PELI1	A001-C-108	Human	Colorectum	FAP	1.87e-13	-3.70e-01	-0.0272
57162	PELI1	A002-C-205	Human	Colorectum	FAP	8.06e-25	-5.67e-01	-0.1236
57162	PELI1	A015-C-005	Human	Colorectum	FAP	4.36e-02	-1.49e-01	-0.0336
57162	PELI1	A015-C-006	Human	Colorectum	FAP	1.17e-16	-5.66e-01	-0.0994
57162	PELI1	A015-C-106	Human	Colorectum	FAP	1.79e-05	-2.86e-01	-0.0511
57162	PELI1	A002-C-114	Human	Colorectum	FAP	6.59e-18	-5.04e-01	-0.1561

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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
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:0043123	Colorectum	AD	positive regulation of I-kappaB kinase/NF-kappaB signaling	60/3918	186/18723	1.91e-04	2.56e-03	60
GO:0043122	Colorectum	AD	regulation of I-kappaB kinase/NF-kappaB signaling	76/3918	249/18723	2.17e-04	2.85e-03	76
GO:0007249	Colorectum	AD	I-kappaB kinase/NF-kappaB signaling	82/3918	281/18723	6.09e-04	6.40e-03	82
GO:0070534	Colorectum	AD	protein K63-linked ubiquitination	20/3918	56/18723	7.57e-03	4.58e-02	20
GO:00104982	Colorectum	MSS	proteasomal protein catabolic process	157/3467	490/18723	2.39e-13	5.25e-11	157
GO:00431612	Colorectum	MSS	proteasome-mediated ubiquitin-dependent protein catabolic process	127/3467	412/18723	7.70e-10	6.32e-08	127
GO:19033202	Colorectum	MSS	regulation of protein modification by small protein conjugation or removal	82/3467	242/18723	7.49e-09	4.63e-07	82
GO:00313962	Colorectum	MSS	regulation of protein ubiquitination	70/3467	210/18723	1.88e-07	8.26e-06	70
GO:00002092	Colorectum	MSS	protein polyubiquitination	72/3467	236/18723	5.19e-06	1.42e-04	72
GO:00709361	Colorectum	MSS	protein K48-linked ubiquitination	27/3467	65/18723	1.40e-05	3.18e-04	27
GO:00431221	Colorectum	MSS	regulation of I-kappaB kinase/NF-kappaB signaling	71/3467	249/18723	7.12e-05	1.21e-03	71
GO:00072491	Colorectum	MSS	I-kappaB kinase/NF-kappaB signaling	77/3467	281/18723	1.51e-04	2.19e-03	77
GO:00431231	Colorectum	MSS	positive regulation of I-kappaB kinase/NF-kappaB signaling	55/3467	186/18723	1.60e-04	2.29e-03	55
GO:00705341	Colorectum	MSS	protein K63-linked ubiquitination	21/3467	56/18723	6.51e-04	7.06e-03	21
GO:0051090	Colorectum	MSS	regulation of DNA-binding transcription factor activity	106/3467	440/18723	1.88e-03	1.65e-02	106
GO:0002221	Colorectum	MSS	pattern recognition receptor signaling pathway	45/3467	172/18723	8.06e-03	4.91e-02	45
GO:00431614	Colorectum	FAP	proteasome-mediated ubiquitin-dependent protein catabolic process	98/2622	412/18723	5.41e-08	4.20e-06	98
GO:00104984	Colorectum	FAP	proteasomal protein catabolic process	110/2622	490/18723	2.12e-07	1.26e-05	110
GO:19033204	Colorectum	FAP	regulation of protein modification by small protein conjugation or removal	61/2622	242/18723	2.36e-06	9.21e-05	61
GO:00709362	Colorectum	FAP	protein K48-linked ubiquitination	24/2622	65/18723	3.42e-06	1.23e-04	24

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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

PELI1

SNV

Missense_Mutation

c.1156N>T

p.His386Tyr

p.H386Y

Q96FA3

protein_coding

deleterious(0.02)

probably_damaging(0.998)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PELI1

SNV

Missense_Mutation

rs761769713

c.977G>A

p.Arg326His

p.R326H

Q96FA3

protein_coding

deleterious(0.04)

possibly_damaging(0.506)

TCGA-AO-A0J4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PELI1

insertion

Frame_Shift_Ins

novel

c.346_347insCCTACGTGAAACCAGATCGGCTCAGCAGAGAGGA

p.Asp116AlafsTer20

p.D116Afs*20

Q96FA3

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

PELI1

insertion

Frame_Shift_Ins

novel

c.340_341insC

p.Val114AlafsTer3

p.V114Afs*3

Q96FA3

protein_coding

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PELI1

insertion

Frame_Shift_Ins

novel

c.339_340insCTCATACTTTTCATGCAGCCTGTCCCTTTTGTGCACATCAGTTG

p.Val114LeufsTer16

p.V114Lfs*16

Q96FA3

protein_coding

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PELI1

SNV

Missense_Mutation

c.1181C>T

p.Ala394Val

p.A394V

Q96FA3

protein_coding

tolerated(0.84)

benign(0.284)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PELI1

SNV

Missense_Mutation

c.1174N>T

p.His392Tyr

p.H392Y

Q96FA3

protein_coding

deleterious(0.01)

possibly_damaging(0.876)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

PELI1

SNV

Missense_Mutation

rs761769713

c.977N>A

p.Arg326His

p.R326H

Q96FA3

protein_coding

deleterious(0.04)

possibly_damaging(0.506)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

PELI1

SNV

Missense_Mutation

c.895N>A

p.Val299Ile

p.V299I

Q96FA3

protein_coding

tolerated(0.31)

benign(0.007)

TCGA-A6-6654-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

oxaliplatin

PELI1

SNV

Missense_Mutation

rs768293813

c.859A>G

p.Asn287Asp

p.N287D

Q96FA3

protein_coding

deleterious(0)

possibly_damaging(0.627)

TCGA-AA-3833-01

Colorectum

colon adenocarcinoma

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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