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: UBR5

Gene summary for UBR5

Gene summary.

Gene information	Species	Human
	Gene symbol	UBR5
	Gene ID	51366
	Gene name	ubiquitin protein ligase E3 component n-recognin 5
	Gene Alias	DD5
	Cytomap	8q22.3
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	O95071

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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
51366	UBR5	CA_HPV_1	Human	Cervix	CC	2.52e-04	-5.12e-02	0.0264
51366	UBR5	CCI_1	Human	Cervix	CC	8.71e-08	1.10e+00	0.528
51366	UBR5	CCI_2	Human	Cervix	CC	1.00e-14	1.95e+00	0.5249
51366	UBR5	CCI_3	Human	Cervix	CC	1.26e-13	1.23e+00	0.516
51366	UBR5	HTA11_3410_2000001011	Human	Colorectum	AD	2.24e-21	-6.76e-01	0.0155
51366	UBR5	HTA11_2487_2000001011	Human	Colorectum	SER	3.81e-04	-4.76e-01	-0.1808
51366	UBR5	HTA11_2951_2000001011	Human	Colorectum	AD	3.06e-03	-7.44e-01	0.0216
51366	UBR5	HTA11_3361_2000001011	Human	Colorectum	AD	2.02e-09	-7.07e-01	-0.1207
51366	UBR5	HTA11_696_2000001011	Human	Colorectum	AD	1.20e-12	-4.54e-01	-0.1464
51366	UBR5	HTA11_866_2000001011	Human	Colorectum	AD	2.33e-08	-3.76e-01	-0.1001
51366	UBR5	HTA11_5216_2000001011	Human	Colorectum	SER	3.40e-02	-5.05e-01	-0.1462
51366	UBR5	HTA11_7862_2000001011	Human	Colorectum	AD	1.03e-03	-6.23e-01	-0.0179
51366	UBR5	HTA11_866_3004761011	Human	Colorectum	AD	1.22e-15	-6.61e-01	0.096
51366	UBR5	HTA11_8622_2000001021	Human	Colorectum	SER	6.08e-04	-6.69e-01	0.0528
51366	UBR5	HTA11_10623_2000001011	Human	Colorectum	AD	2.15e-02	-5.58e-01	-0.0177
51366	UBR5	HTA11_10711_2000001011	Human	Colorectum	AD	8.44e-07	-5.67e-01	0.0338
51366	UBR5	HTA11_7696_3000711011	Human	Colorectum	AD	4.32e-15	-5.39e-01	0.0674
51366	UBR5	HTA11_6818_2000001021	Human	Colorectum	AD	1.64e-03	-4.86e-01	0.0588
51366	UBR5	HTA11_99999970781_79442	Human	Colorectum	MSS	2.20e-08	-3.47e-01	0.294
51366	UBR5	HTA11_99999973899_84307	Human	Colorectum	MSS	3.81e-06	-6.60e-01	0.2585

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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
Prostate		BPH: Benign Prostatic Hyperplasia
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:019873812	Lung	AIS	cell-cell signaling by wnt	91/1849	446/18723	1.22e-11	6.13e-09	91
GO:003011112	Lung	AIS	regulation of Wnt signaling pathway	70/1849	328/18723	3.81e-10	8.87e-08	70
GO:190332013	Lung	AIS	regulation of protein modification by small protein conjugation or removal	55/1849	242/18723	2.75e-09	4.92e-07	55
GO:003139613	Lung	AIS	regulation of protein ubiquitination	46/1849	210/18723	1.71e-07	1.72e-05	46
GO:001657012	Lung	AIS	histone modification	81/1849	463/18723	2.30e-07	2.16e-05	81
GO:006082812	Lung	AIS	regulation of canonical Wnt signaling pathway	52/1849	253/18723	2.40e-07	2.22e-05	52
GO:006007012	Lung	AIS	canonical Wnt signaling pathway	59/1849	303/18723	2.73e-07	2.37e-05	59
GO:000020912	Lung	AIS	protein polyubiquitination	49/1849	236/18723	3.85e-07	3.16e-05	49
GO:003052213	Lung	AIS	intracellular receptor signaling pathway	53/1849	265/18723	4.57e-07	3.55e-05	53
GO:003051812	Lung	AIS	intracellular steroid hormone receptor signaling pathway	28/1849	116/18723	6.14e-06	2.82e-04	28
GO:007138313	Lung	AIS	cellular response to steroid hormone stimulus	41/1849	204/18723	7.76e-06	3.35e-04	41
GO:004854513	Lung	AIS	response to steroid hormone	59/1849	339/18723	1.15e-05	4.65e-04	59
GO:190332113	Lung	AIS	negative regulation of protein modification by small protein conjugation or removal	24/1849	95/18723	1.22e-05	4.71e-04	24
GO:003139713	Lung	AIS	negative regulation of protein ubiquitination	22/1849	83/18723	1.22e-05	4.71e-04	22
GO:000691313	Lung	AIS	nucleocytoplasmic transport	52/1849	301/18723	4.54e-05	1.34e-03	52
GO:005116913	Lung	AIS	nuclear transport	52/1849	301/18723	4.54e-05	1.34e-03	52
GO:003017712	Lung	AIS	positive regulation of Wnt signaling pathway	29/1849	140/18723	9.01e-05	2.21e-03	29
GO:004340112	Lung	AIS	steroid hormone mediated signaling pathway	28/1849	136/18723	1.32e-04	2.97e-03	28
GO:007093612	Lung	AIS	protein K48-linked ubiquitination	17/1849	65/18723	1.39e-04	3.05e-03	17
GO:003315712	Lung	AIS	regulation of intracellular protein transport	40/1849	229/18723	2.58e-04	4.97e-03	40

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041207	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041208	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa041209	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa0412016	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0412017	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0412023	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412033	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122

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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

UBR5

SNV

Missense_Mutation

novel

c.5624N>T

p.Ser1875Phe

p.S1875F

O95071

protein_coding

deleterious(0)

probably_damaging(0.974)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

UBR5

SNV

Missense_Mutation

novel

c.5161A>C

p.Thr1721Pro

p.T1721P

O95071

protein_coding

tolerated(0.08)

benign(0)

TCGA-A2-A0CW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

UBR5

SNV

Missense_Mutation

c.1608N>T

p.Leu536Phe

p.L536F

O95071

protein_coding

deleterious(0.01)

possibly_damaging(0.656)

TCGA-A7-A0D9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

UBR5

SNV

Missense_Mutation

novel

c.1367C>T

p.Ser456Phe

p.S456F

O95071

protein_coding

tolerated(0.12)

benign(0.094)

TCGA-A8-A06U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBR5

SNV

Missense_Mutation

c.7679N>T

p.Gly2560Val

p.G2560V

O95071

protein_coding

deleterious(0)

possibly_damaging(0.908)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UBR5

SNV

Missense_Mutation

novel

c.5161N>C

p.Thr1721Pro

p.T1721P

O95071

protein_coding

tolerated(0.08)

benign(0)

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

UBR5

SNV

Missense_Mutation

c.1795N>C

p.Lys599Gln

p.K599Q

O95071

protein_coding

tolerated(0.07)

probably_damaging(0.95)

TCGA-A8-A09Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

UBR5

SNV

Missense_Mutation

novel

c.2473N>T

p.Asp825Tyr

p.D825Y

O95071

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBR5

SNV

Missense_Mutation

c.6185N>A

p.Arg2062Lys

p.R2062K

O95071

protein_coding

tolerated(0.19)

possibly_damaging(0.815)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

UBR5

SNV

Missense_Mutation

novel

c.5161N>C

p.Thr1721Pro

p.T1721P

O95071

protein_coding

tolerated(0.08)

benign(0)

TCGA-AO-A12H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

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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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