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: RPS14

Gene summary for RPS14

Gene summary.

Gene information	Species	Human
	Gene symbol	RPS14
	Gene ID	6208
	Gene name	ribosomal protein S14
	Gene Alias	EMTB
	Cytomap	5q33.1
	Gene Type	protein-coding
	GO ID	GO:0000028
	UniProtAcc	P62263

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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
6208	RPS14	GSM4909281	Human	Breast	IDC	2.00e-39	-2.55e-01	0.21
6208	RPS14	GSM4909282	Human	Breast	IDC	1.68e-55	-2.83e-01	-0.0288
6208	RPS14	GSM4909286	Human	Breast	IDC	4.06e-02	-4.03e-02	0.1081
6208	RPS14	GSM4909287	Human	Breast	IDC	4.59e-22	-2.97e-01	0.2057
6208	RPS14	GSM4909290	Human	Breast	IDC	5.38e-25	-2.79e-01	0.2096
6208	RPS14	GSM4909293	Human	Breast	IDC	3.14e-07	-7.30e-02	0.1581
6208	RPS14	GSM4909297	Human	Breast	IDC	1.29e-11	-1.84e-01	0.1517
6208	RPS14	GSM4909304	Human	Breast	IDC	6.06e-38	-2.03e-01	0.1636
6208	RPS14	GSM4909305	Human	Breast	IDC	9.51e-03	6.66e-02	0.0436
6208	RPS14	GSM4909315	Human	Breast	IDC	2.33e-08	-1.52e-01	0.21
6208	RPS14	GSM4909316	Human	Breast	IDC	5.29e-11	-4.30e-01	0.21
6208	RPS14	GSM4909317	Human	Breast	IDC	2.74e-06	-1.79e-01	0.1355
6208	RPS14	GSM4909319	Human	Breast	IDC	5.32e-24	-3.58e-01	0.1563
6208	RPS14	brca2	Human	Breast	Precancer	4.28e-14	-1.18e-01	-0.024
6208	RPS14	brca3	Human	Breast	Precancer	7.78e-05	-6.17e-02	-0.0263
6208	RPS14	brca10	Human	Breast	Precancer	5.22e-12	-2.18e-01	-0.0029
6208	RPS14	M2	Human	Breast	IDC	1.32e-11	-4.99e-01	0.21
6208	RPS14	M5	Human	Breast	IDC	1.15e-03	-3.77e-01	0.1598
6208	RPS14	NCCBC14	Human	Breast	DCIS	7.07e-38	-5.68e-01	0.2021
6208	RPS14	NCCBC3	Human	Breast	DCIS	9.48e-04	-6.44e-02	0.1198

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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
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:00021819	Breast	Precancer	cytoplasmic translation	80/1080	148/18723	1.59e-59	8.54e-56	80
GO:00226139	Breast	Precancer	ribonucleoprotein complex biogenesis	79/1080	463/18723	2.11e-18	1.03e-15	79
GO:00718269	Breast	Precancer	ribonucleoprotein complex subunit organization	48/1080	227/18723	2.68e-15	8.45e-13	48
GO:00226189	Breast	Precancer	ribonucleoprotein complex assembly	47/1080	220/18723	3.47e-15	1.03e-12	47
GO:00422549	Breast	Precancer	ribosome biogenesis	52/1080	299/18723	7.35e-13	1.51e-10	52
GO:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:00422559	Breast	Precancer	ribosome assembly	21/1080	61/18723	1.06e-11	1.53e-09	21
GO:00422749	Breast	Precancer	ribosomal small subunit biogenesis	21/1080	73/18723	4.84e-10	4.39e-08	21
GO:00000289	Breast	Precancer	ribosomal small subunit assembly	10/1080	19/18723	2.24e-08	1.50e-06	10
GO:00063646	Breast	Precancer	rRNA processing	35/1080	225/18723	7.90e-08	4.60e-06	35
GO:00160726	Breast	Precancer	rRNA metabolic process	36/1080	236/18723	8.59e-08	4.84e-06	36
GO:00022629	Breast	Precancer	myeloid cell homeostasis	27/1080	157/18723	3.10e-07	1.49e-05	27
GO:00341019	Breast	Precancer	erythrocyte homeostasis	23/1080	129/18723	1.20e-06	4.60e-05	23
GO:00300999	Breast	Precancer	myeloid cell differentiation	45/1080	381/18723	4.00e-06	1.25e-04	45
GO:00344705	Breast	Precancer	ncRNA processing	42/1080	395/18723	9.91e-05	1.83e-03	42
GO:00488729	Breast	Precancer	homeostasis of number of cells	32/1080	272/18723	1.03e-04	1.89e-03	32
GO:00302189	Breast	Precancer	erythrocyte differentiation	18/1080	120/18723	1.76e-04	2.87e-03	18
GO:00346604	Breast	Precancer	ncRNA metabolic process	45/1080	485/18723	1.15e-03	1.26e-02	45
GO:00304902	Breast	Precancer	maturation of SSU-rRNA	8/1080	50/18723	7.39e-03	4.90e-02	8
GO:000218114	Breast	IDC	cytoplasmic translation	82/1434	148/18723	2.60e-52	1.48e-48	82

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0301018	Breast	Precancer	Ribosome	80/684	167/8465	7.33e-44	2.32e-41	1.77e-41	80
hsa0517118	Breast	Precancer	Coronavirus disease - COVID-19	81/684	232/8465	3.74e-32	2.36e-30	1.81e-30	81
hsa0301019	Breast	Precancer	Ribosome	80/684	167/8465	7.33e-44	2.32e-41	1.77e-41	80
hsa0517119	Breast	Precancer	Coronavirus disease - COVID-19	81/684	232/8465	3.74e-32	2.36e-30	1.81e-30	81
hsa0301024	Breast	IDC	Ribosome	83/867	167/8465	6.07e-39	9.87e-37	7.38e-37	83
hsa0517124	Breast	IDC	Coronavirus disease - COVID-19	86/867	232/8465	1.50e-28	9.72e-27	7.27e-27	86
hsa0301034	Breast	IDC	Ribosome	83/867	167/8465	6.07e-39	9.87e-37	7.38e-37	83
hsa0517134	Breast	IDC	Coronavirus disease - COVID-19	86/867	232/8465	1.50e-28	9.72e-27	7.27e-27	86
hsa0301044	Breast	DCIS	Ribosome	82/846	167/8465	8.69e-39	1.40e-36	1.03e-36	82
hsa0517144	Breast	DCIS	Coronavirus disease - COVID-19	86/846	232/8465	2.42e-29	1.56e-27	1.15e-27	86
hsa0301054	Breast	DCIS	Ribosome	82/846	167/8465	8.69e-39	1.40e-36	1.03e-36	82
hsa0517154	Breast	DCIS	Coronavirus disease - COVID-19	86/846	232/8465	2.42e-29	1.56e-27	1.15e-27	86
hsa0517120	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa0301020	Cervix	CC	Ribosome	85/1267	167/8465	3.17e-28	5.14e-26	3.04e-26	85
hsa05171110	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa03010110	Cervix	CC	Ribosome	85/1267	167/8465	3.17e-28	5.14e-26	3.04e-26	85
hsa0301025	Cervix	HSIL_HPV	Ribosome	80/459	167/8465	9.61e-58	2.82e-55	2.28e-55	80
hsa0517125	Cervix	HSIL_HPV	Coronavirus disease - COVID-19	91/459	232/8465	2.14e-56	3.13e-54	2.53e-54	91
hsa0301035	Cervix	HSIL_HPV	Ribosome	80/459	167/8465	9.61e-58	2.82e-55	2.28e-55	80
hsa0517135	Cervix	HSIL_HPV	Coronavirus disease - COVID-19	91/459	232/8465	2.14e-56	3.13e-54	2.53e-54	91

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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

RPS14

SNV

Missense_Mutation

rs137915903

c.221N>G

p.Ala74Gly

p.A74G

P62263

protein_coding

deleterious(0.01)

probably_damaging(0.928)

TCGA-BH-A0BG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RPS14

insertion

Frame_Shift_Ins

novel

c.364_365insTAAAAGATTTTTTCAGACTTTTTTTCAGTGTCTTTTTACTTAATGAA

p.Ser122LeufsTer19

p.S122Lfs*19

P62263

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

RPS14

SNV

Missense_Mutation

novel

c.382N>T

p.Arg128Trp

p.R128W

P62263

protein_coding

deleterious(0.04)

benign(0.056)

TCGA-VS-A9UJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RPS14

SNV

Missense_Mutation

c.221N>A

p.Ala74Asp

p.A74D

P62263

protein_coding

deleterious(0)

benign(0.443)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

RPS14

SNV

Missense_Mutation

novel

c.293G>A

p.Arg98Gln

p.R98Q

P62263

protein_coding

tolerated(0.14)

benign(0.168)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

RPS14

SNV

Missense_Mutation

c.64N>A

p.Ala22Thr

p.A22T

P62263

protein_coding

tolerated(0.12)

benign(0.009)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RPS14

SNV

Missense_Mutation

c.292C>T

p.Arg98Trp

p.R98W

P62263

protein_coding

tolerated(0.06)

benign(0.159)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

RPS14

SNV

Missense_Mutation

novel

c.421C>T

p.Arg141Cys

p.R141C

P62263

protein_coding

tolerated(0.13)

possibly_damaging(0.898)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RPS14

SNV

Missense_Mutation

novel

c.55N>T

p.Pro19Ser

p.P19S

P62263

protein_coding

deleterious(0.02)

benign(0.139)

TCGA-EY-A215-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RPS14

SNV

Missense_Mutation

novel

c.446N>A

p.Arg149His

p.R149H

P62263

protein_coding

tolerated(0.34)

possibly_damaging(0.522)

TCGA-FI-A2D0-01

Endometrium

uterine corpus endometrioid 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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