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: UBA1

Gene summary for UBA1

Gene summary.

Gene information	Species	Human
	Gene symbol	UBA1
	Gene ID	7317
	Gene name	ubiquitin like modifier activating enzyme 1
	Gene Alias	A1S9
	Cytomap	Xp11.3
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	A0A024R1A3

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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
7317	UBA1	HTA11_3410_2000001011	Human	Colorectum	AD	9.45e-07	2.35e-01	0.0155
7317	UBA1	HTA11_2487_2000001011	Human	Colorectum	SER	1.21e-32	1.01e+00	-0.1808
7317	UBA1	HTA11_2951_2000001011	Human	Colorectum	AD	9.76e-03	5.49e-01	0.0216
7317	UBA1	HTA11_1938_2000001011	Human	Colorectum	AD	2.02e-20	7.79e-01	-0.0811
7317	UBA1	HTA11_78_2000001011	Human	Colorectum	AD	1.61e-17	5.47e-01	-0.1088
7317	UBA1	HTA11_347_2000001011	Human	Colorectum	AD	1.15e-34	7.72e-01	-0.1954
7317	UBA1	HTA11_411_2000001011	Human	Colorectum	SER	2.39e-16	1.74e+00	-0.2602
7317	UBA1	HTA11_2112_2000001011	Human	Colorectum	SER	1.76e-06	9.27e-01	-0.2196
7317	UBA1	HTA11_3361_2000001011	Human	Colorectum	AD	4.83e-10	5.80e-01	-0.1207
7317	UBA1	HTA11_83_2000001011	Human	Colorectum	SER	9.57e-12	5.39e-01	-0.1526
7317	UBA1	HTA11_696_2000001011	Human	Colorectum	AD	6.08e-28	7.48e-01	-0.1464
7317	UBA1	HTA11_866_2000001011	Human	Colorectum	AD	2.32e-05	3.71e-01	-0.1001
7317	UBA1	HTA11_1391_2000001011	Human	Colorectum	AD	8.44e-30	9.97e-01	-0.059
7317	UBA1	HTA11_2992_2000001011	Human	Colorectum	SER	5.65e-06	6.36e-01	-0.1706
7317	UBA1	HTA11_5212_2000001011	Human	Colorectum	AD	4.22e-07	5.85e-01	-0.2061
7317	UBA1	HTA11_5216_2000001011	Human	Colorectum	SER	9.61e-09	7.47e-01	-0.1462
7317	UBA1	HTA11_546_2000001011	Human	Colorectum	AD	7.84e-12	5.69e-01	-0.0842
7317	UBA1	HTA11_7862_2000001011	Human	Colorectum	AD	2.25e-03	2.42e-01	-0.0179
7317	UBA1	HTA11_866_3004761011	Human	Colorectum	AD	1.99e-19	5.18e-01	0.096
7317	UBA1	HTA11_7663_2000001011	Human	Colorectum	SER	3.74e-04	3.96e-01	0.0131

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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
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:00307057	Cervix	CC	cytoskeleton-dependent intracellular transport	40/2311	195/18723	7.92e-04	6.99e-03	40
GO:00713533	Cervix	HSIL_HPV	cellular response to interleukin-4	7/737	33/18723	2.48e-04	4.30e-03	7
GO:00706703	Cervix	HSIL_HPV	response to interleukin-4	7/737	36/18723	4.38e-04	6.51e-03	7
GO:003070513	Cervix	N_HPV	cytoskeleton-dependent intracellular transport	13/534	195/18723	4.03e-03	3.16e-02	13
GO:00307058	Endometrium	AEH	cytoskeleton-dependent intracellular transport	38/2100	195/18723	4.72e-04	4.91e-03	38
GO:00508086	Endometrium	AEH	synapse organization	67/2100	426/18723	2.67e-03	1.94e-02	67
GO:003070514	Endometrium	EEC	cytoskeleton-dependent intracellular transport	39/2168	195/18723	4.40e-04	4.58e-03	39
GO:005080812	Endometrium	EEC	synapse organization	68/2168	426/18723	3.73e-03	2.49e-02	68
GO:003070517	Esophagus	HGIN	cytoskeleton-dependent intracellular transport	45/2587	195/18723	3.07e-04	5.15e-03	45
GO:003070518	Esophagus	ESCC	cytoskeleton-dependent intracellular transport	133/8552	195/18723	1.48e-10	4.27e-09	133
GO:00713532	Liver	Cirrhotic	cellular response to interleukin-4	17/4634	33/18723	8.32e-04	6.06e-03	17
GO:003070511	Liver	Cirrhotic	cytoskeleton-dependent intracellular transport	68/4634	195/18723	9.54e-04	6.77e-03	68
GO:00706702	Liver	Cirrhotic	response to interleukin-4	17/4634	36/18723	2.82e-03	1.63e-02	17
GO:003070521	Liver	HCC	cytoskeleton-dependent intracellular transport	111/7958	195/18723	3.25e-05	3.28e-04	111
GO:007135311	Liver	HCC	cellular response to interleukin-4	21/7958	33/18723	1.16e-02	4.28e-02	21
GO:003070510	Oral cavity	OSCC	cytoskeleton-dependent intracellular transport	113/7305	195/18723	6.03e-08	1.09e-06	113
GO:00713535	Oral cavity	OSCC	cellular response to interleukin-4	21/7305	33/18723	3.63e-03	1.51e-02	21
GO:00706705	Oral cavity	OSCC	response to interleukin-4	21/7305	36/18723	1.46e-02	4.76e-02	21
GO:007135313	Oral cavity	LP	cellular response to interleukin-4	18/4623	33/18723	2.26e-04	2.41e-03	18
GO:003070516	Oral cavity	LP	cytoskeleton-dependent intracellular transport	68/4623	195/18723	8.92e-04	7.64e-03	68

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05012	Colorectum	AD	Parkinson disease	147/2092	266/8465	2.53e-27	8.48e-25	5.41e-25	147
hsa05022	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa050121	Colorectum	AD	Parkinson disease	147/2092	266/8465	2.53e-27	8.48e-25	5.41e-25	147
hsa050221	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa050122	Colorectum	SER	Parkinson disease	132/1580	266/8465	2.72e-31	9.03e-29	6.55e-29	132
hsa050222	Colorectum	SER	Pathways of neurodegeneration - multiple diseases	168/1580	476/8465	6.23e-19	2.07e-17	1.50e-17	168
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa050123	Colorectum	SER	Parkinson disease	132/1580	266/8465	2.72e-31	9.03e-29	6.55e-29	132
hsa050223	Colorectum	SER	Pathways of neurodegeneration - multiple diseases	168/1580	476/8465	6.23e-19	2.07e-17	1.50e-17	168
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa050124	Colorectum	MSS	Parkinson disease	140/1875	266/8465	2.32e-28	7.79e-26	4.77e-26	140
hsa050224	Colorectum	MSS	Pathways of neurodegeneration - multiple diseases	192/1875	476/8465	2.79e-20	1.04e-18	6.36e-19	192
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa050125	Colorectum	MSS	Parkinson disease	140/1875	266/8465	2.32e-28	7.79e-26	4.77e-26	140
hsa050225	Colorectum	MSS	Pathways of neurodegeneration - multiple diseases	192/1875	476/8465	2.79e-20	1.04e-18	6.36e-19	192
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa050126	Colorectum	MSI-H	Parkinson disease	85/797	266/8465	1.19e-25	1.29e-23	1.08e-23	85
hsa050226	Colorectum	MSI-H	Pathways of neurodegeneration - multiple diseases	107/797	476/8465	1.24e-18	5.72e-17	4.80e-17	107

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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

UBA1

SNV

Missense_Mutation

novel

c.2132N>T

p.Cys711Phe

p.C711F

P22314

protein_coding

deleterious(0.02)

benign(0.001)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

UBA1

SNV

Missense_Mutation

novel

c.2851G>A

p.Glu951Lys

p.E951K

P22314

protein_coding

tolerated(0.23)

benign(0.094)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBA1

SNV

Missense_Mutation

c.2464N>A

p.Asp822Asn

p.D822N

P22314

protein_coding

deleterious(0.04)

benign(0.12)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UBA1

SNV

Missense_Mutation

rs781991007

c.636T>G

p.Asn212Lys

p.N212K

P22314

protein_coding

deleterious(0.01)

benign(0.333)

TCGA-AR-A1AP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

UBA1

SNV

Missense_Mutation

rs782282295

c.385N>A

p.Glu129Lys

p.E129K

P22314

protein_coding

tolerated(0.12)

possibly_damaging(0.701)

TCGA-BH-A0W7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

UBA1

SNV

Missense_Mutation

c.2988N>A

p.Met996Ile

p.M996I

P22314

protein_coding

tolerated(0.17)

benign(0.237)

TCGA-C8-A12P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UBA1

SNV

Missense_Mutation

novel

c.1750N>T

p.Met584Leu

p.M584L

P22314

protein_coding

tolerated(0.08)

benign(0.363)

TCGA-E2-A154-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

UBA1

insertion

In_Frame_Ins

novel

c.1065_1066insCCTGTCACTGCCTACACTGGACCCCTCGTTGAG

p.Ala355_Ala356insProValThrAlaTyrThrGlyProLeuValGlu

p.A355_A356insPVTAYTGPLVE

P22314

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBA1

SNV

Missense_Mutation

c.2467N>A

p.Asp823Asn

p.D823N

P22314

protein_coding

tolerated(0.11)

benign(0.147)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

UBA1

SNV

Missense_Mutation

novel

c.1570N>A

p.Val524Ile

p.V524I

P22314

protein_coding

tolerated(0.27)

benign(0.341)

TCGA-MA-AA43-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

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
7317	UBA1	ENZYME		HYRTIOERECTINE B	HYRTIOERECTINE B	22695182
7317	UBA1	ENZYME		HIMEIC ACID A	HIMEIC ACID A	22695182

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