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: SETX

Gene summary for SETX

Gene summary.

Gene information	Species	Human
	Gene symbol	SETX
	Gene ID	23064
	Gene name	senataxin
	Gene Alias	ALS4
	Cytomap	9q34.13
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q7Z333

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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
23064	SETX	CA_HPV_1	Human	Cervix	CC	1.46e-05	1.81e-01	0.0264
23064	SETX	CCI_1	Human	Cervix	CC	2.62e-03	5.60e-01	0.528
23064	SETX	CCI_2	Human	Cervix	CC	2.99e-15	1.75e+00	0.5249
23064	SETX	CCI_3	Human	Cervix	CC	3.06e-16	9.89e-01	0.516
23064	SETX	HTA11_3410_2000001011	Human	Colorectum	AD	1.23e-05	-4.08e-01	0.0155
23064	SETX	HTA11_866_3004761011	Human	Colorectum	AD	4.60e-02	-4.13e-01	0.096
23064	SETX	HTA11_7696_3000711011	Human	Colorectum	AD	3.52e-08	-4.28e-01	0.0674
23064	SETX	HTA11_99999974143_84620	Human	Colorectum	MSS	3.77e-07	-4.30e-01	0.3005
23064	SETX	A002-C-010	Human	Colorectum	FAP	6.06e-04	-1.30e-01	0.242
23064	SETX	A015-C-203	Human	Colorectum	FAP	1.07e-24	-2.12e-01	-0.1294
23064	SETX	A015-C-204	Human	Colorectum	FAP	4.63e-03	-5.04e-02	-0.0228
23064	SETX	A014-C-040	Human	Colorectum	FAP	6.55e-03	-3.18e-01	-0.1184
23064	SETX	A002-C-201	Human	Colorectum	FAP	3.30e-08	-8.87e-02	0.0324
23064	SETX	A002-C-203	Human	Colorectum	FAP	3.86e-03	-1.37e-01	0.2786
23064	SETX	A001-C-119	Human	Colorectum	FAP	1.76e-03	-4.88e-02	-0.1557
23064	SETX	A001-C-108	Human	Colorectum	FAP	1.99e-15	9.67e-02	-0.0272
23064	SETX	A002-C-205	Human	Colorectum	FAP	2.20e-17	-5.64e-02	-0.1236
23064	SETX	A001-C-104	Human	Colorectum	FAP	4.62e-03	1.50e-01	0.0184
23064	SETX	A015-C-005	Human	Colorectum	FAP	3.69e-03	-5.12e-02	-0.0336
23064	SETX	A015-C-006	Human	Colorectum	FAP	6.83e-12	-5.72e-02	-0.0994

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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
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:003461425	Skin	AK	cellular response to reactive oxygen species	28/1910	155/18723	1.95e-03	1.32e-02	28
GO:00063524	Skin	AK	DNA-templated transcription, initiation	23/1910	130/18723	6.10e-03	3.29e-02	23
GO:00109765	Skin	AK	positive regulation of neuron projection development	27/1910	163/18723	7.82e-03	3.97e-02	27
GO:0000302112	Skin	SCCIS	response to reactive oxygen species	29/919	222/18723	1.50e-06	8.89e-05	29
GO:0048511110	Skin	SCCIS	rhythmic process	35/919	298/18723	1.63e-06	9.13e-05	35
GO:0006979112	Skin	SCCIS	response to oxidative stress	45/919	446/18723	3.89e-06	1.76e-04	45
GO:0007623110	Skin	SCCIS	circadian rhythm	27/919	210/18723	4.64e-06	1.94e-04	27
GO:004349115	Skin	SCCIS	protein kinase B signaling	27/919	211/18723	5.07e-06	2.09e-04	27
GO:001097518	Skin	SCCIS	regulation of neuron projection development	44/919	445/18723	8.33e-06	3.03e-04	44
GO:0022618112	Skin	SCCIS	ribonucleoprotein complex assembly	27/919	220/18723	1.11e-05	3.87e-04	27
GO:0071826112	Skin	SCCIS	ribonucleoprotein complex subunit organization	27/919	227/18723	1.96e-05	5.92e-04	27
GO:0022613112	Skin	SCCIS	ribonucleoprotein complex biogenesis	44/919	463/18723	2.23e-05	6.50e-04	44
GO:0042542112	Skin	SCCIS	response to hydrogen peroxide	19/919	146/18723	9.81e-05	2.13e-03	19
GO:0043484112	Skin	SCCIS	regulation of RNA splicing	19/919	148/18723	1.18e-04	2.48e-03	19
GO:0062197112	Skin	SCCIS	cellular response to chemical stress	31/919	337/18723	6.10e-04	9.06e-03	31
GO:003252611	Skin	SCCIS	response to retinoic acid	13/919	107/18723	2.23e-03	2.24e-02	13
GO:003134618	Skin	SCCIS	positive regulation of cell projection organization	30/919	353/18723	2.54e-03	2.44e-02	30
GO:0034599112	Skin	SCCIS	cellular response to oxidative stress	25/919	288/18723	4.24e-03	3.57e-02	25
GO:002261329	Skin	cSCC	ribonucleoprotein complex biogenesis	302/4864	463/18723	5.13e-72	3.22e-68	302
GO:0008380112	Skin	cSCC	RNA splicing	263/4864	434/18723	2.45e-53	5.13e-50	263

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501418	Cervix	CC	Amyotrophic lateral sclerosis	103/1267	364/8465	1.79e-11	4.47e-10	2.64e-10	103
hsa0501419	Cervix	CC	Amyotrophic lateral sclerosis	103/1267	364/8465	1.79e-11	4.47e-10	2.64e-10	103
hsa05014	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa050141	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa050148	Colorectum	FAP	Amyotrophic lateral sclerosis	91/1404	364/8465	1.84e-05	2.36e-04	1.44e-04	91
hsa050149	Colorectum	FAP	Amyotrophic lateral sclerosis	91/1404	364/8465	1.84e-05	2.36e-04	1.44e-04	91
hsa0501430	Esophagus	HGIN	Amyotrophic lateral sclerosis	140/1383	364/8465	2.13e-25	1.16e-23	9.19e-24	140
hsa05014113	Esophagus	HGIN	Amyotrophic lateral sclerosis	140/1383	364/8465	2.13e-25	1.16e-23	9.19e-24	140
hsa05014210	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0501438	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0501422	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa0501432	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa0501428	Oral cavity	OSCC	Amyotrophic lateral sclerosis	246/3704	364/8465	6.65e-21	1.11e-18	5.67e-19	246
hsa05014112	Oral cavity	OSCC	Amyotrophic lateral sclerosis	246/3704	364/8465	6.65e-21	1.11e-18	5.67e-19	246
hsa0501445	Oral cavity	EOLP	Amyotrophic lateral sclerosis	93/1218	364/8465	7.07e-09	1.14e-07	6.74e-08	93
hsa0501455	Oral cavity	EOLP	Amyotrophic lateral sclerosis	93/1218	364/8465	7.07e-09	1.14e-07	6.74e-08	93
hsa0501462	Oral cavity	NEOLP	Amyotrophic lateral sclerosis	95/1112	364/8465	8.76e-12	3.98e-10	2.50e-10	95
hsa0501472	Oral cavity	NEOLP	Amyotrophic lateral sclerosis	95/1112	364/8465	8.76e-12	3.98e-10	2.50e-10	95
hsa0501426	Prostate	BPH	Amyotrophic lateral sclerosis	151/1718	364/8465	3.37e-21	1.01e-19	6.25e-20	151
hsa05014111	Prostate	BPH	Amyotrophic lateral sclerosis	151/1718	364/8465	3.37e-21	1.01e-19	6.25e-20	151

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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

SETX

SNV

Missense_Mutation

rs757652780

c.5566G>A

p.Glu1856Lys

p.E1856K

Q7Z333

protein_coding

deleterious(0.05)

probably_damaging(0.994)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SETX

SNV

Missense_Mutation

c.3961G>A

p.Asp1321Asn

p.D1321N

Q7Z333

protein_coding

tolerated(0.21)

benign(0.007)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SETX

SNV

Missense_Mutation

c.2356G>C

p.Glu786Gln

p.E786Q

Q7Z333

protein_coding

deleterious_low_confidence(0.04)

possibly_damaging(0.69)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SETX

SNV

Missense_Mutation

novel

c.7568N>A

p.Thr2523Asn

p.T2523N

Q7Z333

protein_coding

tolerated(0.16)

benign(0.188)

TCGA-A2-A4S1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SETX

SNV

Missense_Mutation

c.689N>G

p.Asp230Gly

p.D230G

Q7Z333

protein_coding

deleterious(0)

probably_damaging(0.914)

TCGA-A8-A07P-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

SETX

SNV

Missense_Mutation

c.5126N>C

p.Lys1709Thr

p.K1709T

Q7Z333

protein_coding

tolerated(0.8)

benign(0.123)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SETX

SNV

Missense_Mutation

c.6590N>G

p.His2197Arg

p.H2197R

Q7Z333

protein_coding

deleterious(0)

probably_damaging(0.956)

TCGA-A8-A09N-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SETX

SNV

Missense_Mutation

novel

c.7393N>A

p.Leu2465Ile

p.L2465I

Q7Z333

protein_coding

tolerated(0.05)

possibly_damaging(0.749)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SETX

SNV

Missense_Mutation

novel

c.7034N>C

p.Ile2345Thr

p.I2345T

Q7Z333

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SETX

SNV

Missense_Mutation

novel

c.6252N>T

p.Lys2084Asn

p.K2084N

Q7Z333

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive 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

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