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: SELENOS

Gene summary for SELENOS

Gene summary.

Gene information	Species	Human
	Gene symbol	SELENOS
	Gene ID	55829
	Gene name	selenoprotein S
	Gene Alias	AD-015
	Cytomap	15q26.3
	Gene Type	protein-coding
	GO ID	GO:0000271
	UniProtAcc	Q9BQE4

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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
55829	SELENOS	GSM5353217_PA_PB1A_Pool_2_S107_L004	Human	Prostate	Tumor	4.11e-02	-7.96e-01	0.156
55829	SELENOS	GSM5353218_PA_PB1B_Pool_1_2_S74_L003	Human	Prostate	Tumor	1.06e-03	-7.96e-01	0.1479
55829	SELENOS	GSM5353220_PA_PB1B_Pool_3_S51_L002	Human	Prostate	Tumor	6.12e-05	-7.96e-01	0.1531
55829	SELENOS	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	1.12e-19	-7.96e-01	0.1633
55829	SELENOS	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	1.56e-27	-7.96e-01	0.1608
55829	SELENOS	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	1.13e-16	-7.96e-01	0.1604
55829	SELENOS	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	6.10e-18	-7.96e-01	0.1621
55829	SELENOS	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	2.24e-09	-7.96e-01	0.1619
55829	SELENOS	GSM5353226_PA_PR5196-2_Pool_1_2_3_S54_L002	Human	Prostate	Tumor	7.47e-06	-7.96e-01	0.159
55829	SELENOS	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	1.19e-20	-7.96e-01	0.1602
55829	SELENOS	GSM5353228_PA_PR5199-640K_Pool_1_3_S108_L004	Human	Prostate	Tumor	9.39e-03	-7.96e-01	0.1537
55829	SELENOS	GSM5353232_PA_PR5249_T1_S3_L001	Human	Prostate	Tumor	1.24e-04	-7.96e-01	0.1439
55829	SELENOS	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	3.15e-10	-7.96e-01	0.1608
55829	SELENOS	GSM5353237_PA_PR5251_T2_S8_L001	Human	Prostate	Tumor	7.47e-06	-7.96e-01	0.1622
55829	SELENOS	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	1.46e-31	-7.96e-01	0.1575
55829	SELENOS	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	1.39e-34	-7.96e-01	0.1545
55829	SELENOS	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	7.10e-27	-7.96e-01	0.1569
55829	SELENOS	GSM5353247_PA_PR5269_3_S27_L002	Human	Prostate	Tumor	4.11e-02	-7.96e-01	0.1532
55829	SELENOS	GSM5353248_PA_PR5269_4_S28_L002	Human	Prostate	Tumor	2.53e-04	-7.96e-01	0.1541
55829	SELENOS	Pat01-B	Human	Stomach	GC	8.65e-50	8.33e-01	0.5754

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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
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Prostate		BPH: Benign Prostatic Hyperplasia
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:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00159808	Breast	Precancer	energy derivation by oxidation of organic compounds	70/1080	318/18723	8.33e-23	6.37e-20	70
GO:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:20012429	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway	41/1080	164/18723	6.48e-16	2.31e-13	41
GO:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00621979	Breast	Precancer	cellular response to chemical stress	51/1080	337/18723	2.40e-10	2.34e-08	51
GO:20012349	Breast	Precancer	negative regulation of apoptotic signaling pathway	39/1080	224/18723	5.35e-10	4.77e-08	39
GO:00069869	Breast	Precancer	response to unfolded protein	28/1080	137/18723	3.81e-09	3.00e-07	28
GO:20012439	Breast	Precancer	negative regulation of intrinsic apoptotic signaling pathway	23/1080	98/18723	5.82e-09	4.45e-07	23
GO:00345999	Breast	Precancer	cellular response to oxidative stress	42/1080	288/18723	2.78e-08	1.79e-06	42
GO:00359669	Breast	Precancer	response to topologically incorrect protein	29/1080	159/18723	3.00e-08	1.89e-06	29
GO:00349769	Breast	Precancer	response to endoplasmic reticulum stress	38/1080	256/18723	7.89e-08	4.60e-06	38
GO:00346209	Breast	Precancer	cellular response to unfolded protein	21/1080	96/18723	9.80e-08	5.46e-06	21
GO:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58
GO:00359679	Breast	Precancer	cellular response to topologically incorrect protein	22/1080	116/18723	6.84e-07	2.80e-05	22
GO:00988698	Breast	Precancer	cellular oxidant detoxification	20/1080	101/18723	1.07e-06	4.18e-05	20
GO:00454548	Breast	Precancer	cell redox homeostasis	11/1080	35/18723	2.59e-06	8.65e-05	11
GO:19907488	Breast	Precancer	cellular detoxification	21/1080	116/18723	2.67e-06	8.89e-05	21
GO:00434677	Breast	Precancer	regulation of generation of precursor metabolites and energy	22/1080	130/18723	4.95e-06	1.51e-04	22

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414118	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414153	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041418	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa041419	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa0414126	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa04141111	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa0414127	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0414136	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64

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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

SELENOS

SNV

Missense_Mutation

rs751562043

c.539N>A

p.Arg180His

p.R180H

Q9BQE4

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-BH-A1FC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SELENOS

SNV

Missense_Mutation

c.455N>T

p.Lys152Ile

p.K152I

Q9BQE4

protein_coding

deleterious(0)

possibly_damaging(0.803)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

SELENOS

SNV

Missense_Mutation

novel

c.101G>A

p.Gly34Asp

p.G34D

Q9BQE4

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A5-A7WJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SELENOS

SNV

Missense_Mutation

c.331N>C

p.Lys111Gln

p.K111Q

Q9BQE4

protein_coding

deleterious(0.01)

possibly_damaging(0.602)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SELENOS

SNV

Missense_Mutation

novel

c.221N>C

p.Val74Ala

p.V74A

Q9BQE4

protein_coding

tolerated(0.54)

benign(0.038)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SELENOS

SNV

Missense_Mutation

novel

c.361N>C

p.Ser121Arg

p.S121R

Q9BQE4

protein_coding

tolerated(0.17)

benign(0.067)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

SELENOS

SNV

Missense_Mutation

c.328N>C

p.Glu110Gln

p.E110Q

Q9BQE4

protein_coding

tolerated(0.24)

benign(0.006)

TCGA-55-A48Y-01

Lung

lung adenocarcinoma

Male

>=65

I/II

Chemotherapy

carboplatin

SELENOS

SNV

Missense_Mutation

novel

c.292N>C

p.Glu98Gln

p.E98Q

Q9BQE4

protein_coding

deleterious(0.02)

possibly_damaging(0.686)

TCGA-22-1016-01

Lung

lung squamous cell carcinoma

Male

>=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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