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: UBE2D3

Gene summary for UBE2D3

Gene summary.

Gene information	Species	Human
	Gene symbol	UBE2D3
	Gene ID	7323
	Gene name	ubiquitin conjugating enzyme E2 D3
	Gene Alias	E2(17)KB3
	Cytomap	4q24
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	D6RAH7

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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
7323	UBE2D3	GSM4909277	Human	Breast	Precancer	1.69e-04	3.11e-01	0.0177
7323	UBE2D3	GSM4909282	Human	Breast	IDC	4.17e-07	-3.63e-01	-0.0288
7323	UBE2D3	GSM4909285	Human	Breast	IDC	3.14e-15	-3.68e-01	0.21
7323	UBE2D3	GSM4909286	Human	Breast	IDC	8.66e-13	-2.11e-01	0.1081
7323	UBE2D3	GSM4909293	Human	Breast	IDC	4.04e-17	-3.63e-01	0.1581
7323	UBE2D3	GSM4909294	Human	Breast	IDC	8.71e-09	-2.58e-01	0.2022
7323	UBE2D3	GSM4909296	Human	Breast	IDC	2.20e-39	-6.89e-01	0.1524
7323	UBE2D3	GSM4909297	Human	Breast	IDC	5.96e-27	-4.44e-01	0.1517
7323	UBE2D3	GSM4909298	Human	Breast	IDC	5.23e-03	-1.45e-01	0.1551
7323	UBE2D3	GSM4909301	Human	Breast	IDC	3.01e-25	-6.20e-01	0.1577
7323	UBE2D3	GSM4909302	Human	Breast	IDC	1.66e-10	-4.81e-01	0.1545
7323	UBE2D3	GSM4909304	Human	Breast	IDC	1.03e-05	-3.18e-01	0.1636
7323	UBE2D3	GSM4909307	Human	Breast	IDC	5.50e-18	-5.39e-01	0.1569
7323	UBE2D3	GSM4909308	Human	Breast	IDC	7.90e-04	-2.69e-01	0.158
7323	UBE2D3	GSM4909309	Human	Breast	IDC	2.30e-11	-4.88e-01	0.0483
7323	UBE2D3	GSM4909311	Human	Breast	IDC	3.23e-59	-7.84e-01	0.1534
7323	UBE2D3	GSM4909312	Human	Breast	IDC	7.67e-14	-2.01e-01	0.1552
7323	UBE2D3	GSM4909313	Human	Breast	IDC	3.26e-02	-2.36e-01	0.0391
7323	UBE2D3	GSM4909315	Human	Breast	IDC	7.11e-27	-6.61e-01	0.21
7323	UBE2D3	GSM4909316	Human	Breast	IDC	5.18e-07	-6.32e-01	0.21

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00068398	Breast	Precancer	mitochondrial transport	45/1080	254/18723	1.37e-11	1.88e-09	45
GO:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58
GO:00100389	Breast	Precancer	response to metal ion	47/1080	373/18723	3.88e-07	1.79e-05	47
GO:00705858	Breast	Precancer	protein localization to mitochondrion	21/1080	125/18723	9.07e-06	2.42e-04	21
GO:00726558	Breast	Precancer	establishment of protein localization to mitochondrion	20/1080	120/18723	1.66e-05	4.03e-04	20
GO:00466868	Breast	Precancer	response to cadmium ion	14/1080	68/18723	2.74e-05	6.21e-04	14
GO:19049519	Breast	Precancer	positive regulation of establishment of protein localization	36/1080	319/18723	9.30e-05	1.75e-03	36
GO:00431619	Breast	Precancer	proteasome-mediated ubiquitin-dependent protein catabolic process	42/1080	412/18723	2.49e-04	3.72e-03	42
GO:00712767	Breast	Precancer	cellular response to cadmium ion	9/1080	40/18723	3.69e-04	5.03e-03	9
GO:00712488	Breast	Precancer	cellular response to metal ion	24/1080	197/18723	4.35e-04	5.79e-03	24
GO:00066268	Breast	Precancer	protein targeting to mitochondrion	15/1080	100/18723	5.94e-04	7.48e-03	15
GO:00712418	Breast	Precancer	cellular response to inorganic substance	26/1080	226/18723	6.23e-04	7.78e-03	26
GO:19038299	Breast	Precancer	positive regulation of cellular protein localization	30/1080	276/18723	6.48e-04	7.99e-03	30
GO:00066059	Breast	Precancer	protein targeting	33/1080	314/18723	6.50e-04	7.99e-03	33
GO:00725948	Breast	Precancer	establishment of protein localization to organelle	41/1080	422/18723	7.75e-04	9.20e-03	41
GO:00512229	Breast	Precancer	positive regulation of protein transport	31/1080	303/18723	1.44e-03	1.50e-02	31
GO:19037474	Breast	Precancer	regulation of establishment of protein localization to mitochondrion	8/1080	50/18723	7.39e-03	4.90e-02	8
GO:000683913	Breast	IDC	mitochondrial transport	51/1434	254/18723	1.54e-10	1.83e-08	51
GO:001003814	Breast	IDC	response to metal ion	65/1434	373/18723	2.95e-10	3.42e-08	65
GO:001049814	Breast	IDC	proteasomal protein catabolic process	75/1434	490/18723	5.59e-09	4.41e-07	75

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513118	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0414118	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0513119	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0513124	Breast	IDC	Shigellosis	47/867	247/8465	1.78e-05	2.00e-04	1.49e-04	47
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0513134	Breast	IDC	Shigellosis	47/867	247/8465	1.78e-05	2.00e-04	1.49e-04	47
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0513144	Breast	DCIS	Shigellosis	46/846	247/8465	2.06e-05	2.38e-04	1.75e-04	46
hsa0414153	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0513154	Breast	DCIS	Shigellosis	46/846	247/8465	2.06e-05	2.38e-04	1.75e-04	46
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

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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

UBE2D3

SNV

Missense_Mutation

novel

c.313C>A

p.Leu105Ile

p.L105I

P61077

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.648)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBE2D3

SNV

Missense_Mutation

c.69T>G

p.Cys23Trp

p.C23W

P61077

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.797)

TCGA-E9-A24A-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

UBE2D3

SNV

Missense_Mutation

novel

c.40N>A

p.Asp14Asn

p.D14N

P61077

protein_coding

deleterious_low_confidence(0.03)

benign(0.149)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

UBE2D3

SNV

Missense_Mutation

novel

c.197C>T

p.Pro66Leu

p.P66L

P61077

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.698)

TCGA-EX-A8YF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

UBE2D3

SNV

Missense_Mutation

novel

c.313C>A

p.Leu105Ile

p.L105I

P61077

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.648)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

UBE2D3

SNV

Missense_Mutation

c.407N>G

p.Tyr136Cys

p.Y136C

P61077

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.996)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2D3

SNV

Missense_Mutation

novel

c.352N>A

p.Asp118Asn

p.D118N

P61077

protein_coding

tolerated_low_confidence(0.06)

benign(0.028)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2D3

SNV

Missense_Mutation

c.305C>A

p.Ser102Tyr

p.S102Y

P61077

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.905)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UBE2D3

SNV

Missense_Mutation

c.50N>C

p.Arg17Pro

p.R17P

P61077

protein_coding

deleterious_low_confidence(0.02)

benign(0.047)

TCGA-E6-A8L9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

UBE2D3

SNV

Missense_Mutation

novel

c.131N>G

p.Asp44Gly

p.D44G

P61077

protein_coding

tolerated_low_confidence(0.1)

benign(0.025)

TCGA-EO-A22R-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

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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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