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: RNPS1

Gene summary for RNPS1

Gene summary.

Gene information	Species	Human
	Gene symbol	RNPS1
	Gene ID	10921
	Gene name	RNA binding protein with serine rich domain 1
	Gene Alias	E5.1
	Cytomap	16p13.3
	Gene Type	protein-coding
	GO ID	GO:0000184
	UniProtAcc	D3DU92

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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
10921	RNPS1	HTA11_3410_2000001011	Human	Colorectum	AD	2.93e-03	1.60e-01	0.0155
10921	RNPS1	HTA11_1938_2000001011	Human	Colorectum	AD	2.89e-08	6.19e-01	-0.0811
10921	RNPS1	HTA11_347_2000001011	Human	Colorectum	AD	5.06e-05	3.13e-01	-0.1954
10921	RNPS1	HTA11_3361_2000001011	Human	Colorectum	AD	4.22e-02	3.31e-01	-0.1207
10921	RNPS1	HTA11_83_2000001011	Human	Colorectum	SER	3.47e-02	3.94e-01	-0.1526
10921	RNPS1	HTA11_696_2000001011	Human	Colorectum	AD	4.67e-05	4.16e-01	-0.1464
10921	RNPS1	HTA11_1391_2000001011	Human	Colorectum	AD	6.52e-11	6.23e-01	-0.059
10921	RNPS1	HTA11_7862_2000001011	Human	Colorectum	AD	6.22e-03	4.41e-01	-0.0179
10921	RNPS1	HTA11_866_3004761011	Human	Colorectum	AD	1.11e-14	6.68e-01	0.096
10921	RNPS1	HTA11_10623_2000001011	Human	Colorectum	AD	4.57e-03	5.19e-01	-0.0177
10921	RNPS1	HTA11_6801_2000001011	Human	Colorectum	SER	7.45e-09	9.62e-01	0.0171
10921	RNPS1	HTA11_10711_2000001011	Human	Colorectum	AD	2.38e-02	3.94e-01	0.0338
10921	RNPS1	HTA11_7696_3000711011	Human	Colorectum	AD	2.49e-13	6.49e-01	0.0674
10921	RNPS1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.36e-20	8.23e-01	0.294
10921	RNPS1	HTA11_99999965104_69814	Human	Colorectum	MSS	1.21e-16	7.77e-01	0.281
10921	RNPS1	HTA11_99999971662_82457	Human	Colorectum	MSS	6.96e-34	1.06e+00	0.3859
10921	RNPS1	HTA11_99999973899_84307	Human	Colorectum	MSS	8.48e-06	7.00e-01	0.2585
10921	RNPS1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.45e-12	4.87e-01	0.3005
10921	RNPS1	A015-C-203	Human	Colorectum	FAP	2.05e-05	-1.68e-01	-0.1294
10921	RNPS1	A002-C-205	Human	Colorectum	FAP	9.40e-05	-1.96e-01	-0.1236

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:0008380	Colorectum	AD	RNA splicing	169/3918	434/18723	3.59e-18	2.04e-15	169
GO:0000377	Colorectum	AD	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000398	Colorectum	AD	mRNA splicing, via spliceosome	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000375	Colorectum	AD	RNA splicing, via transesterification reactions	131/3918	324/18723	7.11e-16	2.22e-13	131
GO:1903311	Colorectum	AD	regulation of mRNA metabolic process	117/3918	288/18723	1.69e-14	4.23e-12	117
GO:0043484	Colorectum	AD	regulation of RNA splicing	70/3918	148/18723	6.47e-13	1.16e-10	70
GO:0048024	Colorectum	AD	regulation of mRNA splicing, via spliceosome	50/3918	101/18723	1.62e-10	1.56e-08	50
GO:0050684	Colorectum	AD	regulation of mRNA processing	61/3918	137/18723	4.23e-10	3.58e-08	61
GO:0006401	Colorectum	AD	RNA catabolic process	102/3918	278/18723	8.64e-10	6.76e-08	102
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0006402	Colorectum	AD	mRNA catabolic process	87/3918	232/18723	4.40e-09	2.84e-07	87
GO:0034655	Colorectum	AD	nucleobase-containing compound catabolic process	133/3918	407/18723	1.56e-08	9.12e-07	133
GO:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153
GO:0000380	Colorectum	AD	alternative mRNA splicing, via spliceosome	33/3918	77/18723	1.13e-05	2.55e-04	33
GO:1903312	Colorectum	AD	negative regulation of mRNA metabolic process	37/3918	92/18723	1.95e-05	4.01e-04	37
GO:0033119	Colorectum	AD	negative regulation of RNA splicing	15/3918	25/18723	2.37e-05	4.62e-04	15
GO:0000381	Colorectum	AD	regulation of alternative mRNA splicing, via spliceosome	27/3918	60/18723	2.41e-05	4.66e-04	27
GO:0000956	Colorectum	AD	nuclear-transcribed mRNA catabolic process	40/3918	112/18723	2.11e-04	2.79e-03	40

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa03015	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030151	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030152	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030153	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa030154	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301511	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301523	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa030132	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53

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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

RNPS1

SNV

Missense_Mutation

novel

c.106N>T

p.Asp36Tyr

p.D36Y

Q15287

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.446)

TCGA-AC-A2FO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

chemo

RNPS1

SNV

Missense_Mutation

c.649G>A

p.Glu217Lys

p.E217K

Q15287

protein_coding

deleterious(0.03)

possibly_damaging(0.564)

TCGA-AR-A5QM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

RNPS1

insertion

Frame_Shift_Ins

novel

c.730_731insCCTGGGAGCACACTTTTCCCTTCCCCGAT

p.Arg244ThrfsTer37

p.R244Tfs*37

Q15287

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

RNPS1

insertion

Frame_Shift_Ins

novel

c.2_3insCTTGCCCTCAG

p.Met1?

p.M1?

Q15287

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

RNPS1

SNV

Missense_Mutation

novel

c.703G>A

p.Ala235Thr

p.A235T

Q15287

protein_coding

deleterious(0.02)

probably_damaging(0.914)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RNPS1

SNV

Missense_Mutation

rs777754533

c.155N>T

p.Ser52Leu

p.S52L

Q15287

protein_coding

deleterious_low_confidence(0)

benign(0.32)

TCGA-AA-3877-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

RNPS1

SNV

Missense_Mutation

c.196C>T

p.Arg66Cys

p.R66C

Q15287

protein_coding

tolerated_low_confidence(0.06)

probably_damaging(0.973)

TCGA-AZ-6601-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

RNPS1

SNV

Missense_Mutation

rs745449452

c.851N>A

p.Arg284His

p.R284H

Q15287

protein_coding

tolerated_low_confidence(0.19)

probably_damaging(0.964)

TCGA-G4-6320-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

oxaliplatin

RNPS1

SNV

Missense_Mutation

c.487N>A

p.Val163Met

p.V163M

Q15287

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-AG-3898-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

RNPS1

deletion

Frame_Shift_Del

c.23delA

p.Lys8ArgfsTer5

p.K8Rfs*5

Q15287

protein_coding

TCGA-AA-3506-01

Colorectum

colon adenocarcinoma

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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