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: SENP5

Gene summary for SENP5

Gene summary.

Gene information	Species	Human
	Gene symbol	SENP5
	Gene ID	205564
	Gene name	SUMO specific peptidase 5
	Gene Alias	SENP5
	Cytomap	3q29
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	B2R9F5

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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
205564	SENP5	CCI_1	Human	Cervix	CC	3.92e-11	9.73e-01	0.528
205564	SENP5	CCI_2	Human	Cervix	CC	9.45e-23	2.06e+00	0.5249
205564	SENP5	CCI_3	Human	Cervix	CC	1.13e-21	1.19e+00	0.516
205564	SENP5	T1	Human	Cervix	CC	3.87e-04	2.59e-01	0.0918
205564	SENP5	LZE2T	Human	Esophagus	ESCC	8.26e-06	5.10e-01	0.082
205564	SENP5	LZE4T	Human	Esophagus	ESCC	1.65e-09	3.09e-01	0.0811
205564	SENP5	LZE7T	Human	Esophagus	ESCC	1.58e-08	4.80e-01	0.0667
205564	SENP5	LZE8T	Human	Esophagus	ESCC	4.44e-06	1.25e-01	0.067
205564	SENP5	LZE20T	Human	Esophagus	ESCC	1.01e-07	1.21e-01	0.0662
205564	SENP5	LZE21D1	Human	Esophagus	HGIN	1.11e-05	2.97e-01	0.0632
205564	SENP5	LZE22T	Human	Esophagus	ESCC	6.47e-05	2.38e-01	0.068
205564	SENP5	LZE24T	Human	Esophagus	ESCC	5.65e-25	5.66e-01	0.0596
205564	SENP5	LZE21T	Human	Esophagus	ESCC	7.25e-09	3.92e-01	0.0655
205564	SENP5	P1T-E	Human	Esophagus	ESCC	4.97e-11	4.58e-01	0.0875
205564	SENP5	P2T-E	Human	Esophagus	ESCC	3.70e-55	8.73e-01	0.1177
205564	SENP5	P4T-E	Human	Esophagus	ESCC	3.60e-16	3.78e-01	0.1323
205564	SENP5	P5T-E	Human	Esophagus	ESCC	7.55e-18	2.45e-01	0.1327
205564	SENP5	P8T-E	Human	Esophagus	ESCC	6.16e-14	3.07e-01	0.0889
205564	SENP5	P9T-E	Human	Esophagus	ESCC	3.47e-09	2.81e-01	0.1131
205564	SENP5	P10T-E	Human	Esophagus	ESCC	6.13e-22	3.61e-01	0.116

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:00182054	Cervix	CC	peptidyl-lysine modification	62/2311	376/18723	1.04e-02	4.97e-02	62
GO:00182057	Esophagus	HGIN	peptidyl-lysine modification	88/2587	376/18723	2.99e-07	1.39e-05	88
GO:00706463	Esophagus	HGIN	protein modification by small protein removal	34/2587	157/18723	4.68e-03	4.02e-02	34
GO:001820514	Esophagus	ESCC	peptidyl-lysine modification	259/8552	376/18723	3.90e-20	5.26e-18	259
GO:007064612	Esophagus	ESCC	protein modification by small protein removal	95/8552	157/18723	1.25e-04	8.56e-04	95
GO:0018205	Liver	NAFLD	peptidyl-lysine modification	65/1882	376/18723	9.42e-06	3.02e-04	65
GO:0070646	Liver	NAFLD	protein modification by small protein removal	29/1882	157/18723	9.11e-04	1.09e-02	29
GO:00182052	Liver	HCC	peptidyl-lysine modification	230/7958	376/18723	1.51e-13	8.32e-12	230
GO:00706461	Liver	HCC	protein modification by small protein removal	91/7958	157/18723	6.50e-05	5.92e-04	91
GO:00182056	Oral cavity	OSCC	peptidyl-lysine modification	216/7305	376/18723	2.32e-13	1.16e-11	216
GO:00706462	Oral cavity	OSCC	protein modification by small protein removal	77/7305	157/18723	6.55e-03	2.43e-02	77
GO:001820521	Oral cavity	EOLP	peptidyl-lysine modification	72/2218	376/18723	2.38e-05	3.56e-04	72
GO:007064611	Oral cavity	EOLP	protein modification by small protein removal	33/2218	157/18723	7.04e-04	5.78e-03	33
GO:001820531	Oral cavity	NEOLP	peptidyl-lysine modification	64/2005	376/18723	1.21e-04	1.43e-03	64
GO:00182058	Skin	AK	peptidyl-lysine modification	66/1910	376/18723	7.80e-06	1.72e-04	66
GO:001820515	Skin	cSCC	peptidyl-lysine modification	137/4864	376/18723	4.09e-06	6.09e-05	137
GO:00706464	Skin	cSCC	protein modification by small protein removal	55/4864	157/18723	7.29e-03	3.46e-02	55
GO:00182059	Thyroid	PTC	peptidyl-lysine modification	188/5968	376/18723	1.34e-13	7.09e-12	188
GO:00706465	Thyroid	PTC	protein modification by small protein removal	71/5968	157/18723	3.03e-04	2.12e-03	71
GO:001820516	Thyroid	ATC	peptidyl-lysine modification	193/6293	376/18723	6.92e-13	3.06e-11	193

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

SENP5

SNV

Missense_Mutation

novel

c.799N>G

p.Trp267Gly

p.W267G

Q96HI0

protein_coding

deleterious(0.03)

probably_damaging(0.996)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SENP5

SNV

Missense_Mutation

c.1205N>C

p.Gln402Pro

p.Q402P

Q96HI0

protein_coding

tolerated(0.24)

benign(0.026)

TCGA-A8-A09N-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SENP5

SNV

Missense_Mutation

rs369618833

c.1430N>G

p.Lys477Arg

p.K477R

Q96HI0

protein_coding

tolerated(0.08)

benign(0.054)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SENP5

insertion

In_Frame_Ins

novel

c.1244_1245insTATGGAAGCTGA

p.Val415_Ser416insMetGluAlaGlu

p.V415_S416insMEAE

Q96HI0

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

SENP5

insertion

Frame_Shift_Ins

novel

c.1246_1247insGGGGAAGGGC

p.Ser416TrpfsTer12

p.S416Wfs*12

Q96HI0

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

SENP5

insertion

Frame_Shift_Ins

novel

c.953_954insAGCTCATGCAAGGTTTATCATCCTAA

p.Thr319AlafsTer31

p.T319Afs*31

Q96HI0

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

SENP5

insertion

Nonsense_Mutation

novel

c.657_658insTGCCTCTGCTTCTGAGCCTTTCTGCTTTCTG

p.Asn220CysfsTer5

p.N220Cfs*5

Q96HI0

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SENP5

insertion

Nonsense_Mutation

novel

c.1438_1439insCCTTCCCCAGAACCTAAAGACCCTTCTTGTCGGC

p.Asn480ThrfsTer6

p.N480Tfs*6

Q96HI0

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SENP5

insertion

Frame_Shift_Ins

novel

c.1354_1355insC

p.Ile452ThrfsTer3

p.I452Tfs*3

Q96HI0

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

SENP5

insertion

In_Frame_Ins

novel

c.1356_1357insCAGAACCAAAAGCAAGGTTTGCAAGCTAAGAAAAGC

p.Ile452_Leu453insGlnAsnGlnLysGlnGlyLeuGlnAlaLysLysSer

p.I452_L453insQNQKQGLQAKKS

Q96HI0

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

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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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