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: UBE2L6

Gene summary for UBE2L6

Gene summary.

Gene information	Species	Human
	Gene symbol	UBE2L6
	Gene ID	9246
	Gene name	ubiquitin conjugating enzyme E2 L6
	Gene Alias	RIG-B
	Cytomap	11q12.1
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	O14933

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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
9246	UBE2L6	GSM4909281	Human	Breast	IDC	2.78e-31	7.83e-01	0.21
9246	UBE2L6	GSM4909286	Human	Breast	IDC	1.49e-12	-2.05e-01	0.1081
9246	UBE2L6	GSM4909296	Human	Breast	IDC	1.05e-03	8.74e-02	0.1524
9246	UBE2L6	GSM4909297	Human	Breast	IDC	1.30e-04	5.20e-02	0.1517
9246	UBE2L6	GSM4909311	Human	Breast	IDC	7.62e-13	-1.10e-01	0.1534
9246	UBE2L6	GSM4909312	Human	Breast	IDC	1.59e-07	-4.49e-02	0.1552
9246	UBE2L6	GSM4909315	Human	Breast	IDC	3.97e-11	5.01e-01	0.21
9246	UBE2L6	GSM4909316	Human	Breast	IDC	1.03e-11	7.18e-01	0.21
9246	UBE2L6	GSM4909319	Human	Breast	IDC	1.41e-26	-2.25e-02	0.1563
9246	UBE2L6	GSM4909321	Human	Breast	IDC	1.93e-09	1.82e-01	0.1559
9246	UBE2L6	NCCBC5	Human	Breast	DCIS	7.04e-11	4.16e-01	0.2046
9246	UBE2L6	P1	Human	Breast	IDC	1.60e-04	-5.78e-02	0.1527
9246	UBE2L6	P2	Human	Breast	IDC	6.84e-18	7.56e-01	0.21
9246	UBE2L6	DCIS2	Human	Breast	DCIS	3.74e-26	2.41e-02	0.0085
9246	UBE2L6	CA_HPV_1	Human	Cervix	CC	4.33e-06	2.63e-01	0.0264
9246	UBE2L6	CCII_1	Human	Cervix	CC	3.81e-03	-2.55e-01	0.3249
9246	UBE2L6	Tumor	Human	Cervix	CC	9.68e-23	5.63e-01	0.1241
9246	UBE2L6	sample1	Human	Cervix	CC	3.46e-13	7.23e-01	0.0959
9246	UBE2L6	sample3	Human	Cervix	CC	1.74e-12	4.10e-01	0.1387
9246	UBE2L6	L1	Human	Cervix	CC	3.69e-02	-1.24e-01	0.0802

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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
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
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:000020916	Esophagus	HGIN	protein polyubiquitination	58/2587	236/18723	6.29e-06	1.97e-04	58
GO:000020917	Esophagus	ESCC	protein polyubiquitination	170/8552	236/18723	1.40e-16	1.09e-14	170
GO:000020911	Liver	Cirrhotic	protein polyubiquitination	89/4634	236/18723	6.09e-06	9.80e-05	89
GO:000020921	Liver	HCC	protein polyubiquitination	151/7958	236/18723	1.90e-11	7.59e-10	151
GO:000020910	Oral cavity	OSCC	protein polyubiquitination	150/7305	236/18723	1.59e-14	9.27e-13	150
GO:000020915	Oral cavity	LP	protein polyubiquitination	82/4623	236/18723	3.23e-04	3.26e-03	82
GO:000020924	Skin	cSCC	protein polyubiquitination	103/4864	236/18723	2.57e-09	9.09e-08	103
GO:000020920	Thyroid	PTC	protein polyubiquitination	128/5968	236/18723	7.81e-13	3.65e-11	128
GO:0000209110	Thyroid	ATC	protein polyubiquitination	134/6293	236/18723	1.86e-13	9.20e-12	134

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501224	Breast	IDC	Parkinson disease	107/867	266/8465	2.57e-39	8.36e-37	6.26e-37	107
hsa0502223	Breast	IDC	Pathways of neurodegeneration - multiple diseases	116/867	476/8465	3.63e-20	1.18e-18	8.82e-19	116
hsa0501234	Breast	IDC	Parkinson disease	107/867	266/8465	2.57e-39	8.36e-37	6.26e-37	107
hsa0502233	Breast	IDC	Pathways of neurodegeneration - multiple diseases	116/867	476/8465	3.63e-20	1.18e-18	8.82e-19	116
hsa0501243	Breast	DCIS	Parkinson disease	106/846	266/8465	1.64e-39	5.29e-37	3.90e-37	106
hsa0502243	Breast	DCIS	Pathways of neurodegeneration - multiple diseases	114/846	476/8465	4.74e-20	1.53e-18	1.13e-18	114
hsa0501253	Breast	DCIS	Parkinson disease	106/846	266/8465	1.64e-39	5.29e-37	3.90e-37	106
hsa0502253	Breast	DCIS	Pathways of neurodegeneration - multiple diseases	114/846	476/8465	4.74e-20	1.53e-18	1.13e-18	114
hsa0501220	Cervix	CC	Parkinson disease	102/1267	266/8465	1.81e-21	1.47e-19	8.66e-20	102
hsa0502218	Cervix	CC	Pathways of neurodegeneration - multiple diseases	128/1267	476/8465	2.87e-12	9.29e-11	5.50e-11	128
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa05012110	Cervix	CC	Parkinson disease	102/1267	266/8465	1.81e-21	1.47e-19	8.66e-20	102
hsa0502219	Cervix	CC	Pathways of neurodegeneration - multiple diseases	128/1267	476/8465	2.87e-12	9.29e-11	5.50e-11	128
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0501239	Esophagus	HGIN	Parkinson disease	124/1383	266/8465	5.95e-32	9.70e-30	7.70e-30	124
hsa0502230	Esophagus	HGIN	Pathways of neurodegeneration - multiple diseases	153/1383	476/8465	1.22e-18	4.41e-17	3.50e-17	153
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa05012114	Esophagus	HGIN	Parkinson disease	124/1383	266/8465	5.95e-32	9.70e-30	7.70e-30	124
hsa05022113	Esophagus	HGIN	Pathways of neurodegeneration - multiple diseases	153/1383	476/8465	1.22e-18	4.41e-17	3.50e-17	153
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49

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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

UBE2L6

SNV

Missense_Mutation

c.277G>C

p.Glu93Gln

p.E93Q

O14933

protein_coding

tolerated(0.06)

benign(0.026)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBE2L6

SNV

Missense_Mutation

c.133N>G

p.Pro45Ala

p.P45A

O14933

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-E9-A22E-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphane

UBE2L6

SNV

Missense_Mutation

rs770937454

c.437G>A

p.Arg146Gln

p.R146Q

O14933

protein_coding

tolerated(0.24)

benign(0)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2L6

SNV

Missense_Mutation

c.310N>T

p.Val104Phe

p.V104F

O14933

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UBE2L6

SNV

Missense_Mutation

c.154A>G

p.Asn52Asp

p.N52D

O14933

protein_coding

deleterious(0.02)

benign(0.055)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2L6

SNV

Missense_Mutation

novel

c.289N>T

p.Pro97Ser

p.P97S

O14933

protein_coding

deleterious(0)

possibly_damaging(0.682)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2L6

SNV

Missense_Mutation

rs868642148

c.398N>T

p.Pro133Leu

p.P133L

O14933

protein_coding

tolerated(0.47)

benign(0.058)

TCGA-BG-A0VW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UBE2L6

SNV

Missense_Mutation

c.48N>T

p.Lys16Asn

p.K16N

O14933

protein_coding

tolerated(0.18)

benign(0.007)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UBE2L6

SNV

Missense_Mutation

novel

c.210N>A

p.Phe70Leu

p.F70L

O14933

protein_coding

deleterious(0.02)

probably_damaging(0.998)

TCGA-EO-A22R-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBE2L6

SNV

Missense_Mutation

rs199916226

c.148N>A

p.Ala50Thr

p.A50T

O14933

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EO-A22X-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unspecific

Carboplatin

Complete Response

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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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