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: UBE2D2

Gene summary for UBE2D2

Gene summary.

Gene information	Species	Human
	Gene symbol	UBE2D2
	Gene ID	7322
	Gene name	ubiquitin conjugating enzyme E2 D2
	Gene Alias	E2(17)KB2
	Cytomap	5q31.2
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	P62837

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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
7322	UBE2D2	CA_HPV_1	Human	Cervix	CC	1.76e-06	-1.79e-01	0.0264
7322	UBE2D2	CCI_2	Human	Cervix	CC	1.89e-16	1.19e+00	0.5249
7322	UBE2D2	CCII_1	Human	Cervix	CC	8.00e-07	-5.14e-01	0.3249
7322	UBE2D2	sample3	Human	Cervix	CC	9.67e-06	-1.36e-01	0.1387
7322	UBE2D2	L1	Human	Cervix	CC	8.53e-03	-1.45e-01	0.0802
7322	UBE2D2	T1	Human	Cervix	CC	2.53e-04	-3.61e-01	0.0918
7322	UBE2D2	HTA11_3410_2000001011	Human	Colorectum	AD	5.35e-12	-4.59e-01	0.0155
7322	UBE2D2	HTA11_347_2000001011	Human	Colorectum	AD	3.04e-03	4.23e-01	-0.1954
7322	UBE2D2	HTA11_866_3004761011	Human	Colorectum	AD	3.52e-02	-3.30e-01	0.096
7322	UBE2D2	HTA11_99999965062_69753	Human	Colorectum	MSI-H	5.21e-04	8.37e-01	0.3487
7322	UBE2D2	HTA11_99999973899_84307	Human	Colorectum	MSS	1.71e-02	-3.31e-01	0.2585
7322	UBE2D2	HTA11_99999974143_84620	Human	Colorectum	MSS	2.26e-03	-3.61e-01	0.3005
7322	UBE2D2	F007	Human	Colorectum	FAP	6.54e-08	-5.20e-01	0.1176
7322	UBE2D2	A002-C-010	Human	Colorectum	FAP	1.32e-08	-3.64e-01	0.242
7322	UBE2D2	A001-C-207	Human	Colorectum	FAP	5.26e-07	-4.20e-01	0.1278
7322	UBE2D2	A015-C-203	Human	Colorectum	FAP	7.09e-38	-5.58e-01	-0.1294
7322	UBE2D2	A015-C-204	Human	Colorectum	FAP	4.72e-05	-2.14e-01	-0.0228
7322	UBE2D2	A014-C-040	Human	Colorectum	FAP	2.03e-08	-6.40e-01	-0.1184
7322	UBE2D2	A002-C-201	Human	Colorectum	FAP	1.08e-20	-5.50e-01	0.0324
7322	UBE2D2	A002-C-203	Human	Colorectum	FAP	5.10e-13	-3.96e-01	0.2786

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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
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:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:00709366	Cervix	CC	protein K48-linked ubiquitination	22/2311	65/18723	5.56e-06	1.38e-04	22
GO:00518656	Cervix	CC	protein autoubiquitination	17/2311	73/18723	6.71e-03	3.70e-02	17
GO:0000209	Colorectum	AD	protein polyubiquitination	78/3918	236/18723	8.71e-06	2.06e-04	78
GO:0070936	Colorectum	AD	protein K48-linked ubiquitination	27/3918	65/18723	1.31e-04	1.88e-03	27
GO:0051865	Colorectum	AD	protein autoubiquitination	28/3918	73/18723	4.87e-04	5.30e-03	28
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:00518651	Colorectum	MSS	protein autoubiquitination	25/3467	73/18723	1.00e-03	1.00e-02	25
GO:00709362	Colorectum	FAP	protein K48-linked ubiquitination	24/2622	65/18723	3.42e-06	1.23e-04	24
GO:00002093	Colorectum	FAP	protein polyubiquitination	59/2622	236/18723	4.53e-06	1.52e-04	59
GO:00518652	Colorectum	FAP	protein autoubiquitination	22/2622	73/18723	2.88e-04	3.77e-03	22
GO:00709363	Colorectum	CRC	protein K48-linked ubiquitination	19/2078	65/18723	5.34e-05	1.22e-03	19
GO:00002094	Colorectum	CRC	protein polyubiquitination	46/2078	236/18723	9.91e-05	1.98e-03	46
GO:00518653	Colorectum	CRC	protein autoubiquitination	18/2078	73/18723	8.33e-04	1.04e-02	18
GO:00709367	Endometrium	AEH	protein K48-linked ubiquitination	21/2100	65/18723	4.56e-06	1.18e-04	21
GO:00002098	Endometrium	AEH	protein polyubiquitination	44/2100	236/18723	4.83e-04	4.97e-03	44
GO:007093614	Endometrium	EEC	protein K48-linked ubiquitination	22/2168	65/18723	1.92e-06	5.79e-05	22
GO:000020913	Endometrium	EEC	protein polyubiquitination	46/2168	236/18723	2.65e-04	3.04e-03	46
GO:007093610	Esophagus	HGIN	protein K48-linked ubiquitination	24/2587	65/18723	2.69e-06	9.49e-05	24

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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
hsa0513120	Cervix	CC	Shigellosis	69/1267	247/8465	7.64e-08	1.03e-06	6.10e-07	69
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
hsa05131110	Cervix	CC	Shigellosis	69/1267	247/8465	7.64e-08	1.03e-06	6.10e-07	69
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa051311	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa051314	Colorectum	MSS	Shigellosis	94/1875	247/8465	6.82e-09	1.34e-07	8.23e-08	94
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa051315	Colorectum	MSS	Shigellosis	94/1875	247/8465	6.82e-09	1.34e-07	8.23e-08	94
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041416	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa051316	Colorectum	MSI-H	Shigellosis	40/797	247/8465	4.28e-04	5.34e-03	4.47e-03	40

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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

UBE2D2

SNV

Missense_Mutation

c.93N>G

p.Phe31Leu

p.F31L

P62837

protein_coding

tolerated_low_confidence(0.06)

benign(0.108)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

UBE2D2

SNV

Missense_Mutation

novel

c.181C>T

p.Pro61Ser

p.P61S

P62837

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.971)

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

UBE2D2

SNV

Missense_Mutation

c.85G>A

p.Asp29Asn

p.D29N

P62837

protein_coding

tolerated_low_confidence(0.1)

benign(0.1)

TCGA-E2-A1IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

UBE2D2

SNV

Missense_Mutation

c.244N>A

p.Gly82Ser

p.G82S

P62837

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.981)

TCGA-AU-6004-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

UBE2D2

SNV

Missense_Mutation

novel

c.349G>T

p.Asp117Tyr

p.D117Y

P62837

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.985)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

UBE2D2

SNV

Missense_Mutation

novel

c.407G>T

p.Arg136Ile

p.R136I

P62837

protein_coding

deleterious_low_confidence(0.03)

benign(0.374)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

UBE2D2

SNV

Missense_Mutation

c.215N>T

p.Arg72Ile

p.R72I

P62837

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.591)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

UBE2D2

SNV

Missense_Mutation

c.340N>G

p.Asn114Asp

p.N114D

P62837

protein_coding

deleterious_low_confidence(0.04)

possibly_damaging(0.872)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

UBE2D2

SNV

Missense_Mutation

novel

c.202G>A

p.Ala68Thr

p.A68T

P62837

protein_coding

tolerated_low_confidence(0.32)

benign(0.031)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UBE2D2

SNV

Missense_Mutation

novel

c.160A>G

p.Ile54Val

p.I54V

P62837

protein_coding

tolerated_low_confidence(0.08)

benign(0.027)

TCGA-D1-A175-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

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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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