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: UBA2

Gene summary for UBA2

Gene summary.

Gene information	Species	Human
	Gene symbol	UBA2
	Gene ID	10054
	Gene name	ubiquitin like modifier activating enzyme 2
	Gene Alias	ARX
	Cytomap	19q13.11
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q9UBT2

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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
10054	UBA2	HTA11_1938_2000001011	Human	Colorectum	AD	4.98e-03	3.73e-01	-0.0811
10054	UBA2	HTA11_347_2000001011	Human	Colorectum	AD	3.00e-04	3.30e-01	-0.1954
10054	UBA2	HTA11_99999965062_69753	Human	Colorectum	MSI-H	7.73e-04	1.00e+00	0.3487
10054	UBA2	HTA11_99999965104_69814	Human	Colorectum	MSS	7.57e-05	4.93e-01	0.281
10054	UBA2	HTA11_99999971662_82457	Human	Colorectum	MSS	1.25e-02	4.87e-01	0.3859
10054	UBA2	A015-C-203	Human	Colorectum	FAP	9.97e-15	-2.73e-01	-0.1294
10054	UBA2	A014-C-040	Human	Colorectum	FAP	4.94e-03	-4.29e-01	-0.1184
10054	UBA2	A002-C-201	Human	Colorectum	FAP	3.66e-05	-2.49e-01	0.0324
10054	UBA2	A001-C-108	Human	Colorectum	FAP	1.72e-08	-1.49e-01	-0.0272
10054	UBA2	A002-C-205	Human	Colorectum	FAP	4.69e-08	-2.46e-01	-0.1236
10054	UBA2	A015-C-006	Human	Colorectum	FAP	1.38e-05	-1.26e-01	-0.0994
10054	UBA2	A015-C-106	Human	Colorectum	FAP	6.80e-06	-1.98e-01	-0.0511
10054	UBA2	A002-C-114	Human	Colorectum	FAP	3.53e-07	-2.94e-01	-0.1561
10054	UBA2	A015-C-104	Human	Colorectum	FAP	7.37e-16	-2.85e-01	-0.1899
10054	UBA2	A001-C-014	Human	Colorectum	FAP	5.01e-08	-2.46e-01	0.0135
10054	UBA2	A002-C-016	Human	Colorectum	FAP	1.34e-11	-2.67e-01	0.0521
10054	UBA2	A015-C-002	Human	Colorectum	FAP	3.62e-03	-2.86e-01	-0.0763
10054	UBA2	A001-C-203	Human	Colorectum	FAP	6.58e-07	-2.21e-01	-0.0481
10054	UBA2	A002-C-116	Human	Colorectum	FAP	6.56e-16	-2.33e-01	-0.0452
10054	UBA2	A014-C-008	Human	Colorectum	FAP	1.25e-04	-2.74e-01	-0.191

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:190332018	Prostate	BPH	regulation of protein modification by small protein conjugation or removal	90/3107	242/18723	7.37e-15	1.01e-12	90
GO:19033226	Prostate	BPH	positive regulation of protein modification by small protein conjugation or removal	46/3107	138/18723	1.09e-06	1.97e-05	46
GO:00182055	Prostate	BPH	peptidyl-lysine modification	96/3107	376/18723	5.70e-06	8.39e-05	96
GO:00169252	Prostate	BPH	protein sumoylation	18/3107	53/18723	1.56e-03	9.16e-03	18
GO:190332019	Prostate	Tumor	regulation of protein modification by small protein conjugation or removal	92/3246	242/18723	1.20e-14	1.73e-12	92
GO:190332214	Prostate	Tumor	positive regulation of protein modification by small protein conjugation or removal	47/3246	138/18723	1.50e-06	2.67e-05	47
GO:001820512	Prostate	Tumor	peptidyl-lysine modification	99/3246	376/18723	6.77e-06	1.02e-04	99
GO:00169251	Prostate	Tumor	protein sumoylation	18/3246	53/18723	2.59e-03	1.43e-02	18
GO:190332028	Skin	AK	regulation of protein modification by small protein conjugation or removal	62/1910	242/18723	4.90e-12	1.04e-09	62
GO:00182058	Skin	AK	peptidyl-lysine modification	66/1910	376/18723	7.80e-06	1.72e-04	66
GO:19033229	Skin	AK	positive regulation of protein modification by small protein conjugation or removal	25/1910	138/18723	3.18e-03	1.95e-02	25
GO:190332029	Skin	cSCC	regulation of protein modification by small protein conjugation or removal	125/4864	242/18723	9.50e-18	1.05e-15	125
GO:190332217	Skin	cSCC	positive regulation of protein modification by small protein conjugation or removal	64/4864	138/18723	1.79e-07	3.94e-06	64
GO:001820515	Skin	cSCC	peptidyl-lysine modification	137/4864	376/18723	4.09e-06	6.09e-05	137
GO:00169255	Skin	cSCC	protein sumoylation	23/4864	53/18723	4.39e-03	2.29e-02	23
GO:1903320113	Thyroid	PTC	regulation of protein modification by small protein conjugation or removal	148/5968	242/18723	4.49e-21	8.10e-19	148
GO:00182059	Thyroid	PTC	peptidyl-lysine modification	188/5968	376/18723	1.34e-13	7.09e-12	188
GO:190332210	Thyroid	PTC	positive regulation of protein modification by small protein conjugation or removal	73/5968	138/18723	2.34e-07	4.11e-06	73
GO:00169256	Thyroid	PTC	protein sumoylation	30/5968	53/18723	1.71e-04	1.31e-03	30
GO:190332034	Thyroid	ATC	regulation of protein modification by small protein conjugation or removal	152/6293	242/18723	9.76e-21	1.71e-18	152

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041207	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041208	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa041209	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
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
hsa0412021	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0412031	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0412020	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105
hsa04120110	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

UBA2

SNV

Missense_Mutation

novel

c.91N>C

p.Glu31Gln

p.E31Q

Q9UBT2

protein_coding

deleterious(0.03)

probably_damaging(0.998)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

UBA2

SNV

Missense_Mutation

c.526N>T

p.Arg176Cys

p.R176C

Q9UBT2

protein_coding

deleterious(0.02)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBA2

SNV

Missense_Mutation

c.796C>A

p.Leu266Met

p.L266M

Q9UBT2

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

UBA2

deletion

In_Frame_Del

c.681_704delNNNNNNNNNNNNNNNNNNNNNNNN

p.Arg227_Ile235delinsSer

p.R227_I235delinsS

Q9UBT2

protein_coding

TCGA-A8-A07L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

UBA2

insertion

Nonsense_Mutation

novel

c.1343_1344insTAGCTAGCCTAGCCTTTAGCTGATTAGAAA

p.Pro448_Glu449insSerTerProSerLeuTerLeuIleArgLys

p.P448_E449insS*PSL*LIRK

Q9UBT2

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

UBA2

insertion

Frame_Shift_Ins

novel

c.1122_1123insATCTTGGCTTACTGCAGCCTCTGCGTCCCGG

p.Asp375IlefsTer27

p.D375Ifs*27

Q9UBT2

protein_coding

TCGA-B6-A0RE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UBA2

SNV

Missense_Mutation

c.752N>T

p.Pro251Leu

p.P251L

Q9UBT2

protein_coding

deleterious(0)

benign(0.362)

TCGA-EK-A2RB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

UBA2

insertion

Nonsense_Mutation

novel

c.341_342insAAAAACATAGTAAC

p.Asn114LysfsTer4

p.N114Kfs*4

Q9UBT2

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

UBA2

SNV

Missense_Mutation

c.365N>A

p.Arg122Gln

p.R122Q

Q9UBT2

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A6-3809-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

UBA2

SNV

Missense_Mutation

novel

c.173N>G

p.Asn58Ser

p.N58S

Q9UBT2

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3509-01

Colorectum

colon adenocarcinoma

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
10054	UBA2	DRUGGABLE GENOME, ENZYME		LOBARIC ACID	LOBARIC ACID
10054	UBA2	DRUGGABLE GENOME, ENZYME		BETULINIC ACID	BETULINIC ACID
10054	UBA2	DRUGGABLE GENOME, ENZYME		PEVONEDISTAT	PEVONEDISTAT
10054	UBA2	DRUGGABLE GENOME, ENZYME		ASTERRIC ACID	ASTERRIC ACID
10054	UBA2	DRUGGABLE GENOME, ENZYME		LIPOIC ACID, ALPHA	LIPOIC ACID, ALPHA
10054	UBA2	DRUGGABLE GENOME, ENZYME		4-PHENYLAMINO-[1,2]NAPHTHOQUINONE	CHEMBL299853
10054	UBA2	DRUGGABLE GENOME, ENZYME		BENSERAZIDE HYDROCHLORIDE	BENSERAZIDE HYDROCHLORIDE
10054	UBA2	DRUGGABLE GENOME, ENZYME		GINGKOLIC ACID	GINGKOLIC ACID	23920437

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