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: UBR3

Gene summary for UBR3

Gene summary.

Gene information	Species	Human
	Gene symbol	UBR3
	Gene ID	130507
	Gene name	ubiquitin protein ligase E3 component n-recognin 3
	Gene Alias	ZNF650
	Cytomap	2q31.1
	Gene Type	protein-coding
	GO ID	GO:0001967
	UniProtAcc	Q6ZT12

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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
130507	UBR3	CCI_1	Human	Cervix	CC	5.73e-04	6.21e-01	0.528
130507	UBR3	CCI_2	Human	Cervix	CC	5.26e-13	1.46e+00	0.5249
130507	UBR3	CCI_3	Human	Cervix	CC	5.06e-11	7.10e-01	0.516
130507	UBR3	HTA11_3410_2000001011	Human	Colorectum	AD	8.42e-13	-5.41e-01	0.0155
130507	UBR3	HTA11_83_2000001011	Human	Colorectum	SER	6.11e-03	-3.36e-01	-0.1526
130507	UBR3	HTA11_696_2000001011	Human	Colorectum	AD	1.02e-03	-3.07e-01	-0.1464
130507	UBR3	HTA11_866_2000001011	Human	Colorectum	AD	6.95e-05	-2.93e-01	-0.1001
130507	UBR3	HTA11_866_3004761011	Human	Colorectum	AD	8.21e-06	-4.89e-01	0.096
130507	UBR3	HTA11_7696_3000711011	Human	Colorectum	AD	1.87e-08	-4.29e-01	0.0674
130507	UBR3	HTA11_99999970781_79442	Human	Colorectum	MSS	4.62e-06	-3.22e-01	0.294
130507	UBR3	HTA11_99999974143_84620	Human	Colorectum	MSS	4.66e-07	-3.48e-01	0.3005
130507	UBR3	A015-C-203	Human	Colorectum	FAP	1.25e-37	-5.60e-01	-0.1294
130507	UBR3	A015-C-204	Human	Colorectum	FAP	2.58e-06	-3.50e-01	-0.0228
130507	UBR3	A014-C-040	Human	Colorectum	FAP	1.40e-05	-5.85e-01	-0.1184
130507	UBR3	A002-C-201	Human	Colorectum	FAP	1.22e-14	-5.07e-01	0.0324
130507	UBR3	A002-C-203	Human	Colorectum	FAP	3.08e-05	-2.48e-01	0.2786
130507	UBR3	A001-C-119	Human	Colorectum	FAP	1.66e-05	-3.38e-01	-0.1557
130507	UBR3	A001-C-108	Human	Colorectum	FAP	6.95e-18	-3.28e-01	-0.0272
130507	UBR3	A002-C-205	Human	Colorectum	FAP	1.03e-21	-4.55e-01	-0.1236
130507	UBR3	A001-C-104	Human	Colorectum	FAP	4.68e-08	-2.35e-01	0.0184

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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
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
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: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: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:00104981	Colorectum	SER	proteasomal protein catabolic process	132/2897	490/18723	3.08e-11	5.55e-09	132
GO:00431611	Colorectum	SER	proteasome-mediated ubiquitin-dependent protein catabolic process	105/2897	412/18723	7.48e-08	4.70e-06	105
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: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:00431615	Colorectum	CRC	proteasome-mediated ubiquitin-dependent protein catabolic process	69/2078	412/18723	3.16e-04	4.90e-03	69
GO:00104985	Colorectum	CRC	proteasomal protein catabolic process	77/2078	490/18723	1.03e-03	1.21e-02	77
GO:00431617	Liver	NAFLD	proteasome-mediated ubiquitin-dependent protein catabolic process	91/1882	412/18723	3.00e-13	1.75e-10	91
GO:00104987	Liver	NAFLD	proteasomal protein catabolic process	101/1882	490/18723	1.35e-12	6.09e-10	101
GO:001049812	Liver	Cirrhotic	proteasomal protein catabolic process	216/4634	490/18723	2.52e-21	9.29e-19	216
GO:004316112	Liver	Cirrhotic	proteasome-mediated ubiquitin-dependent protein catabolic process	184/4634	412/18723	4.52e-19	8.85e-17	184
GO:001049822	Liver	HCC	proteasomal protein catabolic process	351/7958	490/18723	6.92e-40	1.46e-36	351
GO:004316122	Liver	HCC	proteasome-mediated ubiquitin-dependent protein catabolic process	299/7958	412/18723	7.82e-36	8.27e-33	299
GO:00104988	Lung	IAC	proteasomal protein catabolic process	90/2061	490/18723	6.69e-07	3.89e-05	90
GO:00431618	Lung	IAC	proteasome-mediated ubiquitin-dependent protein catabolic process	78/2061	412/18723	1.10e-06	6.02e-05	78

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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

UBR3

SNV

Missense_Mutation

rs749430097

c.2083N>A

p.Gln695Lys

p.Q695K

Q6ZT12

protein_coding

deleterious(0)

possibly_damaging(0.9)

TCGA-A2-A0CS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

UBR3

SNV

Missense_Mutation

novel

c.784N>G

p.Met262Val

p.M262V

Q6ZT12

protein_coding

deleterious(0.01)

possibly_damaging(0.761)

TCGA-AC-A3EH-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

UBR3

SNV

Missense_Mutation

c.3184N>T

p.Arg1062Cys

p.R1062C

Q6ZT12

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBR3

SNV

Missense_Mutation

rs747734159

c.4655N>A

p.Arg1552His

p.R1552H

Q6ZT12

protein_coding

tolerated(0.28)

benign(0)

TCGA-BH-A0DH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

UBR3

SNV

Missense_Mutation

novel

c.1901T>C

p.Leu634Pro

p.L634P

Q6ZT12

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBR3

SNV

Missense_Mutation

c.4480C>T

p.His1494Tyr

p.H1494Y

Q6ZT12

protein_coding

deleterious(0)

probably_damaging(0.932)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBR3

SNV

Missense_Mutation

rs756966878

c.4217N>T

p.Pro1406Leu

p.P1406L

Q6ZT12

protein_coding

tolerated(0.78)

benign(0)

TCGA-BH-A1F8-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

UBR3

SNV

Missense_Mutation

rs749430097

c.2083N>A

p.Gln695Lys

p.Q695K

Q6ZT12

protein_coding

deleterious(0)

possibly_damaging(0.9)

TCGA-BH-A1FH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

UBR3

SNV

Missense_Mutation

c.4886N>C

p.Cys1629Ser

p.C1629S

Q6ZT12

protein_coding

tolerated(0.41)

benign(0)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

UBR3

SNV

Missense_Mutation

c.3538N>C

p.Glu1180Gln

p.E1180Q

Q6ZT12

protein_coding

deleterious(0.02)

probably_damaging(0.986)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

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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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