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: UBE2D1

Gene summary for UBE2D1

Gene summary.

Gene information	Species	Human
	Gene symbol	UBE2D1
	Gene ID	7321
	Gene name	ubiquitin conjugating enzyme E2 D1
	Gene Alias	E2(17)KB1
	Cytomap	10q21.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	A0A087WW00

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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
7321	UBE2D1	LZE4T	Human	Esophagus	ESCC	1.10e-11	4.31e-01	0.0811
7321	UBE2D1	LZE5T	Human	Esophagus	ESCC	1.49e-10	3.27e-01	0.0514
7321	UBE2D1	LZE7T	Human	Esophagus	ESCC	8.56e-03	3.12e-02	0.0667
7321	UBE2D1	LZE8T	Human	Esophagus	ESCC	2.02e-04	-9.09e-02	0.067
7321	UBE2D1	LZE20T	Human	Esophagus	ESCC	3.71e-11	1.64e-01	0.0662
7321	UBE2D1	LZE22D1	Human	Esophagus	HGIN	5.27e-03	-3.46e-02	0.0595
7321	UBE2D1	LZE24T	Human	Esophagus	ESCC	1.32e-27	1.07e+00	0.0596
7321	UBE2D1	LZE6T	Human	Esophagus	ESCC	1.35e-02	-1.30e-01	0.0845
7321	UBE2D1	P1T-E	Human	Esophagus	ESCC	7.91e-04	3.05e-01	0.0875
7321	UBE2D1	P2T-E	Human	Esophagus	ESCC	1.50e-20	4.94e-01	0.1177
7321	UBE2D1	P4T-E	Human	Esophagus	ESCC	4.21e-25	6.99e-01	0.1323
7321	UBE2D1	P5T-E	Human	Esophagus	ESCC	1.79e-26	6.49e-01	0.1327
7321	UBE2D1	P8T-E	Human	Esophagus	ESCC	4.50e-26	6.33e-01	0.0889
7321	UBE2D1	P9T-E	Human	Esophagus	ESCC	1.12e-18	3.77e-01	0.1131
7321	UBE2D1	P10T-E	Human	Esophagus	ESCC	1.00e-18	1.74e-01	0.116
7321	UBE2D1	P11T-E	Human	Esophagus	ESCC	7.92e-16	1.12e+00	0.1426
7321	UBE2D1	P12T-E	Human	Esophagus	ESCC	8.77e-25	6.66e-01	0.1122
7321	UBE2D1	P15T-E	Human	Esophagus	ESCC	1.32e-19	4.19e-01	0.1149
7321	UBE2D1	P16T-E	Human	Esophagus	ESCC	1.52e-15	3.23e-01	0.1153
7321	UBE2D1	P17T-E	Human	Esophagus	ESCC	1.33e-04	3.86e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
Liver		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

∗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:190332027	Esophagus	HGIN	regulation of protein modification by small protein conjugation or removal	78/2587	242/18723	1.40e-13	2.26e-11	78
GO:003139627	Esophagus	HGIN	regulation of protein ubiquitination	64/2587	210/18723	3.02e-10	2.71e-08	64
GO:007093610	Esophagus	HGIN	protein K48-linked ubiquitination	24/2587	65/18723	2.69e-06	9.49e-05	24
GO:000020916	Esophagus	HGIN	protein polyubiquitination	58/2587	236/18723	6.29e-06	1.97e-04	58
GO:19033228	Esophagus	HGIN	positive regulation of protein modification by small protein conjugation or removal	35/2587	138/18723	2.11e-04	3.88e-03	35
GO:19029142	Esophagus	HGIN	regulation of protein polyubiquitination	11/2587	27/18723	5.28e-04	7.56e-03	11
GO:00313987	Esophagus	HGIN	positive regulation of protein ubiquitination	28/2587	119/18723	2.89e-03	2.81e-02	28
GO:1903320111	Esophagus	ESCC	regulation of protein modification by small protein conjugation or removal	181/8552	242/18723	1.80e-20	2.60e-18	181
GO:000020917	Esophagus	ESCC	protein polyubiquitination	170/8552	236/18723	1.40e-16	1.09e-14	170
GO:0031396111	Esophagus	ESCC	regulation of protein ubiquitination	154/8552	210/18723	2.70e-16	2.04e-14	154
GO:007093617	Esophagus	ESCC	protein K48-linked ubiquitination	55/8552	65/18723	8.42e-11	2.58e-09	55
GO:190332216	Esophagus	ESCC	positive regulation of protein modification by small protein conjugation or removal	99/8552	138/18723	4.39e-10	1.16e-08	99
GO:003139816	Esophagus	ESCC	positive regulation of protein ubiquitination	82/8552	119/18723	2.41e-07	3.64e-06	82
GO:000717810	Esophagus	ESCC	transmembrane receptor protein serine/threonine kinase signaling pathway	195/8552	355/18723	2.58e-04	1.58e-03	195
GO:190332022	Liver	HCC	regulation of protein modification by small protein conjugation or removal	167/7958	242/18723	4.99e-17	4.72e-15	167
GO:003139622	Liver	HCC	regulation of protein ubiquitination	142/7958	210/18723	1.39e-13	7.81e-12	142
GO:000020921	Liver	HCC	protein polyubiquitination	151/7958	236/18723	1.90e-11	7.59e-10	151
GO:007093621	Liver	HCC	protein K48-linked ubiquitination	52/7958	65/18723	6.70e-10	2.11e-08	52
GO:19033221	Liver	HCC	positive regulation of protein modification by small protein conjugation or removal	94/7958	138/18723	9.87e-10	3.01e-08	94
GO:00313981	Liver	HCC	positive regulation of protein ubiquitination	79/7958	119/18723	1.18e-07	2.26e-06	79

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0513139	Esophagus	HGIN	Shigellosis	71/1383	247/8465	4.89e-07	7.98e-06	6.34e-06	71
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa05131114	Esophagus	HGIN	Shigellosis	71/1383	247/8465	4.89e-07	7.98e-06	6.34e-06	71
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
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
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
hsa05131310	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
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
hsa0513142	Liver	HCC	Shigellosis	150/4020	247/8465	1.53e-05	1.04e-04	5.81e-05	150
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0513152	Liver	HCC	Shigellosis	150/4020	247/8465	1.53e-05	1.04e-04	5.81e-05	150
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa0412020	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105

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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

UBE2D1

SNV

Missense_Mutation

novel

c.383N>C

p.Lys128Thr

p.K128T

P51668

protein_coding

deleterious_low_confidence(0.01)

benign(0.232)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBE2D1

SNV

Missense_Mutation

novel

c.325N>G

p.Leu109Val

p.L109V

P51668

protein_coding

deleterious_low_confidence(0.04)

possibly_damaging(0.566)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

UBE2D1

deletion

Frame_Shift_Del

c.165delN

p.Pro57ArgfsTer22

p.P57Rfs*22

P51668

protein_coding

TCGA-AA-A022-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

UBE2D1

SNV

Missense_Mutation

rs766515311

c.130N>A

p.Ala44Thr

p.A44T

P51668

protein_coding

deleterious_low_confidence(0)

benign(0.078)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2D1

SNV

Missense_Mutation

rs766515311

c.130N>A

p.Ala44Thr

p.A44T

P51668

protein_coding

deleterious_low_confidence(0)

benign(0.078)

TCGA-AJ-A3OJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

UBE2D1

SNV

Missense_Mutation

novel

c.371C>T

p.Ala124Val

p.A124V

P51668

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.972)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2D1

SNV

Missense_Mutation

novel

c.323N>A

p.Ser108Tyr

p.S108Y

P51668

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.969)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2D1

SNV

Missense_Mutation

novel

c.29T>C

p.Leu10Ser

p.L10S

P51668

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.95)

TCGA-DI-A1BU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

UBE2D1

SNV

Missense_Mutation

novel

c.85N>T

p.Asp29Tyr

p.D29Y

P51668

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.953)

TCGA-EO-A3AV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

UBE2D1

SNV

Missense_Mutation

novel

c.391N>G

p.Lys131Glu

p.K131E

P51668

protein_coding

deleterious_low_confidence(0)

benign(0.007)

TCGA-EO-A3AY-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
7321	UBE2D1	ENZYME, TRANSCRIPTION FACTOR		DESFERRIOXAMINE	DEFEROXAMINE	9694900

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