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: UBE4B

Gene summary for UBE4B

Gene summary.

Gene information	Species	Human
	Gene symbol	UBE4B
	Gene ID	10277
	Gene name	ubiquitination factor E4B
	Gene Alias	E4
	Cytomap	1p36.22
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	O95155

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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
10277	UBE4B	CCI_1	Human	Cervix	CC	1.34e-09	1.00e+00	0.528
10277	UBE4B	CCI_2	Human	Cervix	CC	1.38e-12	1.37e+00	0.5249
10277	UBE4B	CCI_3	Human	Cervix	CC	8.37e-13	9.72e-01	0.516
10277	UBE4B	AEH-subject1	Human	Endometrium	AEH	5.38e-04	2.38e-01	-0.3059
10277	UBE4B	AEH-subject2	Human	Endometrium	AEH	3.08e-02	1.54e-01	-0.2525
10277	UBE4B	AEH-subject3	Human	Endometrium	AEH	1.79e-02	1.95e-01	-0.2576
10277	UBE4B	AEH-subject4	Human	Endometrium	AEH	1.41e-05	2.87e-01	-0.2657
10277	UBE4B	AEH-subject5	Human	Endometrium	AEH	2.70e-07	3.34e-01	-0.2953
10277	UBE4B	EEC-subject1	Human	Endometrium	EEC	1.27e-02	2.50e-01	-0.2682
10277	UBE4B	EEC-subject4	Human	Endometrium	EEC	3.48e-02	2.35e-01	-0.2571
10277	UBE4B	GSM5276934	Human	Endometrium	EEC	3.65e-04	-9.18e-02	-0.0913
10277	UBE4B	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	3.17e-02	-7.52e-02	-0.1869
10277	UBE4B	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	9.94e-03	3.39e-02	-0.1875
10277	UBE4B	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	6.40e-04	-2.53e-02	-0.1883
10277	UBE4B	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	1.79e-04	-9.11e-03	-0.1934
10277	UBE4B	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	1.66e-10	-9.92e-02	-0.1917
10277	UBE4B	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	2.63e-04	-6.57e-02	-0.1916
10277	UBE4B	LZE2T	Human	Esophagus	ESCC	9.32e-03	3.85e-01	0.082
10277	UBE4B	LZE4T	Human	Esophagus	ESCC	1.49e-12	4.88e-01	0.0811
10277	UBE4B	LZE7T	Human	Esophagus	ESCC	2.34e-07	5.92e-01	0.0667

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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
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
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:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:003497610	Cervix	CC	response to endoplasmic reticulum stress	57/2311	256/18723	5.81e-06	1.42e-04	57
GO:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86
GO:00094112	Cervix	CC	response to UV	33/2311	149/18723	5.51e-04	5.29e-03	33
GO:00094163	Cervix	CC	response to light stimulus	54/2311	320/18723	1.03e-02	4.97e-02	54
GO:001049816	Endometrium	AEH	proteasomal protein catabolic process	108/2100	490/18723	2.73e-12	4.67e-10	108
GO:004316116	Endometrium	AEH	proteasome-mediated ubiquitin-dependent protein catabolic process	88/2100	412/18723	1.54e-09	1.36e-07	88
GO:003497616	Endometrium	AEH	response to endoplasmic reticulum stress	62/2100	256/18723	2.88e-09	2.13e-07	62
GO:00002098	Endometrium	AEH	protein polyubiquitination	44/2100	236/18723	4.83e-04	4.97e-03	44
GO:00365033	Endometrium	AEH	ERAD pathway	23/2100	107/18723	1.55e-03	1.27e-02	23
GO:000931410	Endometrium	AEH	response to radiation	70/2100	456/18723	3.99e-03	2.68e-02	70
GO:00304332	Endometrium	AEH	ubiquitin-dependent ERAD pathway	18/2100	85/18723	5.63e-03	3.46e-02	18
GO:001049817	Endometrium	EEC	proteasomal protein catabolic process	112/2168	490/18723	6.99e-13	1.40e-10	112
GO:004316117	Endometrium	EEC	proteasome-mediated ubiquitin-dependent protein catabolic process	92/2168	412/18723	3.01e-10	3.23e-08	92
GO:003497617	Endometrium	EEC	response to endoplasmic reticulum stress	63/2168	256/18723	3.84e-09	2.71e-07	63
GO:000020913	Endometrium	EEC	protein polyubiquitination	46/2168	236/18723	2.65e-04	3.04e-03	46
GO:003650312	Endometrium	EEC	ERAD pathway	24/2168	107/18723	1.03e-03	9.07e-03	24
GO:003043311	Endometrium	EEC	ubiquitin-dependent ERAD pathway	19/2168	85/18723	3.43e-03	2.32e-02	19

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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
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa0414126	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa0412016	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa04141111	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa0412017	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0414127	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0412023	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0414136	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0412033	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412010	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412011	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110

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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

UBE4B

SNV

Missense_Mutation

c.3502N>A

p.Ala1168Thr

p.A1168T

O95155

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-A8-A096-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBE4B

SNV

Missense_Mutation

c.499N>A

p.Arg167Ser

p.R167S

O95155

protein_coding

tolerated(0.16)

probably_damaging(0.982)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBE4B

SNV

Missense_Mutation

c.461C>G

p.Ser154Cys

p.S154C

O95155

protein_coding

deleterious(0)

possibly_damaging(0.751)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBE4B

SNV

Missense_Mutation

rs781407095

c.2333G>A

p.Arg778His

p.R778H

O95155

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBE4B

SNV

Missense_Mutation

rs760809804

c.407N>A

p.Arg136Gln

p.R136Q

O95155

protein_coding

deleterious(0.02)

probably_damaging(0.968)

TCGA-AR-A250-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

UBE4B

SNV

Missense_Mutation

novel

c.3061A>G

p.Lys1021Glu

p.K1021E

O95155

protein_coding

deleterious(0.01)

possibly_damaging(0.6)

TCGA-AR-A5QN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

taxotere

UBE4B

SNV

Missense_Mutation

rs372819662

c.991N>T

p.Arg331Cys

p.R331C

O95155

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

UBE4B

SNV

Missense_Mutation

c.569N>G

p.Asn190Ser

p.N190S

O95155

protein_coding

tolerated(0.11)

benign(0.138)

TCGA-D8-A1Y0-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide+methotrexatum+fluorouracillum

UBE4B

SNV

Missense_Mutation

rs750897247

c.2443N>T

p.Arg815Cys

p.R815C

O95155

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-E2-A15O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

UBE4B

insertion

Frame_Shift_Ins

novel

c.1329dupA

p.Ala444SerfsTer52

p.A444Sfs*52

O95155

protein_coding

TCGA-A2-A0SY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

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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