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: UBR2

Gene summary for UBR2

Gene summary.

Gene information	Species	Human
	Gene symbol	UBR2
	Gene ID	23304
	Gene name	ubiquitin protein ligase E3 component n-recognin 2
	Gene Alias	C6orf133
	Cytomap	6p21.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q8IWV8

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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
23304	UBR2	CCI_1	Human	Cervix	CC	2.02e-05	7.67e-01	0.528
23304	UBR2	CCI_2	Human	Cervix	CC	9.76e-11	1.15e+00	0.5249
23304	UBR2	CCI_3	Human	Cervix	CC	4.97e-06	7.51e-01	0.516
23304	UBR2	HTA11_3410_2000001011	Human	Colorectum	AD	2.15e-07	-3.62e-01	0.0155
23304	UBR2	HTA11_347_2000001011	Human	Colorectum	AD	1.27e-13	7.02e-01	-0.1954
23304	UBR2	HTA11_99999965104_69814	Human	Colorectum	MSS	1.59e-02	4.96e-01	0.281
23304	UBR2	HTA11_99999974143_84620	Human	Colorectum	MSS	6.95e-09	-4.30e-01	0.3005
23304	UBR2	F007	Human	Colorectum	FAP	1.59e-03	-2.80e-01	0.1176
23304	UBR2	A001-C-207	Human	Colorectum	FAP	2.60e-06	-3.46e-01	0.1278
23304	UBR2	A015-C-203	Human	Colorectum	FAP	6.02e-31	-4.23e-01	-0.1294
23304	UBR2	A015-C-204	Human	Colorectum	FAP	9.42e-11	-3.58e-01	-0.0228
23304	UBR2	A014-C-040	Human	Colorectum	FAP	1.29e-05	-4.67e-01	-0.1184
23304	UBR2	A002-C-201	Human	Colorectum	FAP	1.37e-16	-4.43e-01	0.0324
23304	UBR2	A002-C-203	Human	Colorectum	FAP	5.93e-07	-2.83e-01	0.2786
23304	UBR2	A001-C-119	Human	Colorectum	FAP	2.38e-05	-1.95e-01	-0.1557
23304	UBR2	A001-C-108	Human	Colorectum	FAP	3.22e-15	-2.09e-01	-0.0272
23304	UBR2	A002-C-205	Human	Colorectum	FAP	2.81e-25	-2.59e-01	-0.1236
23304	UBR2	A001-C-104	Human	Colorectum	FAP	1.71e-03	-2.33e-01	0.0184
23304	UBR2	A015-C-005	Human	Colorectum	FAP	3.64e-04	-2.30e-01	-0.0336
23304	UBR2	A015-C-006	Human	Colorectum	FAP	1.38e-19	-5.90e-01	-0.0994

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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
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:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:00165705	Cervix	CC	histone modification	84/2311	463/18723	1.70e-04	2.01e-03	84
GO:00011016	Cervix	CC	response to acid chemical	31/2311	135/18723	4.16e-04	4.22e-03	31
GO:00712292	Cervix	CC	cellular response to acid chemical	20/2311	80/18723	1.40e-03	1.10e-02	20
GO:00712301	Cervix	CC	cellular response to amino acid stimulus	18/2311	71/18723	2.01e-03	1.47e-02	18
GO:00432004	Cervix	CC	response to amino acid	25/2311	116/18723	3.59e-03	2.30e-02	25
GO:00482851	Cervix	CC	organelle fission	78/2311	488/18723	9.70e-03	4.79e-02	78
GO:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:0033522	Colorectum	AD	histone H2A ubiquitination	12/3918	26/18723	3.47e-03	2.51e-02	12
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:0016570	Colorectum	MSS	histone modification	113/3467	463/18723	8.37e-04	8.68e-03	113
GO:00335221	Colorectum	MSS	histone H2A ubiquitination	12/3467	26/18723	1.16e-03	1.12e-02	12
GO:0031929	Colorectum	MSS	TOR signaling	35/3467	126/18723	6.91e-03	4.44e-02	35
GO:0016574	Colorectum	MSS	histone ubiquitination	16/3467	47/18723	8.22e-03	4.99e-02	16
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:00165701	Colorectum	FAP	histone modification	94/2622	463/18723	1.06e-04	1.76e-03	94

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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

UBR2

SNV

Missense_Mutation

c.574N>C

p.Tyr192His

p.Y192H

Q8IWV8

protein_coding

tolerated(0.51)

benign(0.017)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

UBR2

SNV

Missense_Mutation

c.2204C>T

p.Ser735Phe

p.S735F

Q8IWV8

protein_coding

tolerated(0.29)

benign(0.129)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBR2

SNV

Missense_Mutation

novel

c.3472N>A

p.Asp1158Asn

p.D1158N

Q8IWV8

protein_coding

tolerated(0.06)

benign(0.017)

TCGA-AR-A0TS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

UBR2

SNV

Missense_Mutation

novel

c.3039N>C

p.Glu1013Asp

p.E1013D

Q8IWV8

protein_coding

tolerated(0.39)

benign(0.003)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UBR2

SNV

Missense_Mutation

c.4187N>C

p.Leu1396Pro

p.L1396P

Q8IWV8

protein_coding

deleterious(0)

probably_damaging(0.928)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBR2

SNV

Missense_Mutation

novel

c.2206G>A

p.Glu736Lys

p.E736K

Q8IWV8

protein_coding

tolerated(0.72)

benign(0.003)

TCGA-BH-A28O-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

UBR2

SNV

Missense_Mutation

novel

c.4444N>T

p.Ala1482Ser

p.A1482S

Q8IWV8

protein_coding

tolerated(0.95)

benign(0)

TCGA-BH-A42U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBR2

SNV

Missense_Mutation

c.1702A>G

p.Lys568Glu

p.K568E

Q8IWV8

protein_coding

tolerated(1)

benign(0.003)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

UBR2

SNV

Missense_Mutation

c.8N>G

p.Ser3Trp

p.S3W

Q8IWV8

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.461)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBR2

SNV

Missense_Mutation

rs754681331

c.2750C>T

p.Ser917Leu

p.S917L

Q8IWV8

protein_coding

deleterious(0)

possibly_damaging(0.792)

TCGA-E2-A2P6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

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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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