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: SRPK1

Gene summary for SRPK1

Gene summary.

Gene information	Species	Human
	Gene symbol	SRPK1
	Gene ID	6732
	Gene name	SRSF protein kinase 1
	Gene Alias	SFRSK1
	Cytomap	6p21.31
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q96SB4

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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
6732	SRPK1	CA_HPV_3	Human	Cervix	CC	3.29e-02	8.55e-02	0.0414
6732	SRPK1	CCI_1	Human	Cervix	CC	2.03e-03	6.00e-01	0.528
6732	SRPK1	CCI_2	Human	Cervix	CC	1.21e-03	6.95e-01	0.5249
6732	SRPK1	CCI_3	Human	Cervix	CC	1.30e-02	4.39e-01	0.516
6732	SRPK1	HTA11_3410_2000001011	Human	Colorectum	AD	7.19e-11	-4.37e-01	0.0155
6732	SRPK1	HTA11_2487_2000001011	Human	Colorectum	SER	9.38e-06	-5.00e-01	-0.1808
6732	SRPK1	HTA11_5216_2000001011	Human	Colorectum	SER	6.63e-06	-6.00e-01	-0.1462
6732	SRPK1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.51e-08	6.60e-01	0.3487
6732	SRPK1	HTA11_99999965104_69814	Human	Colorectum	MSS	5.02e-05	5.61e-01	0.281
6732	SRPK1	HTA11_99999974143_84620	Human	Colorectum	MSS	5.03e-04	-3.54e-01	0.3005
6732	SRPK1	A002-C-010	Human	Colorectum	FAP	3.98e-02	3.79e-02	0.242
6732	SRPK1	A001-C-207	Human	Colorectum	FAP	1.32e-06	-2.45e-01	0.1278
6732	SRPK1	A015-C-203	Human	Colorectum	FAP	3.20e-31	-1.16e-01	-0.1294
6732	SRPK1	A015-C-204	Human	Colorectum	FAP	1.27e-10	-3.56e-01	-0.0228
6732	SRPK1	A014-C-040	Human	Colorectum	FAP	1.06e-06	-2.71e-01	-0.1184
6732	SRPK1	A002-C-201	Human	Colorectum	FAP	2.04e-17	-2.91e-01	0.0324
6732	SRPK1	A002-C-203	Human	Colorectum	FAP	2.71e-07	-3.35e-01	0.2786
6732	SRPK1	A001-C-119	Human	Colorectum	FAP	1.07e-11	-5.02e-02	-0.1557
6732	SRPK1	A001-C-108	Human	Colorectum	FAP	1.12e-16	-1.97e-01	-0.0272
6732	SRPK1	A002-C-205	Human	Colorectum	FAP	1.53e-29	-7.03e-02	-0.1236

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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:000037734	Thyroid	ATC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	197/6293	320/18723	6.54e-25	2.18e-22	197
GO:000039834	Thyroid	ATC	mRNA splicing, via spliceosome	197/6293	320/18723	6.54e-25	2.18e-22	197
GO:190331134	Thyroid	ATC	regulation of mRNA metabolic process	181/6293	288/18723	1.75e-24	5.54e-22	181
GO:005068434	Thyroid	ATC	regulation of mRNA processing	97/6293	137/18723	5.28e-19	7.25e-17	97
GO:004348435	Thyroid	ATC	regulation of RNA splicing	100/6293	148/18723	2.75e-17	2.72e-15	100
GO:007182635	Thyroid	ATC	ribonucleoprotein complex subunit organization	133/6293	227/18723	8.32e-15	5.01e-13	133
GO:001905835	Thyroid	ATC	viral life cycle	173/6293	317/18723	9.22e-15	5.50e-13	173
GO:002261835	Thyroid	ATC	ribonucleoprotein complex assembly	129/6293	220/18723	1.93e-14	1.10e-12	129
GO:000705913	Thyroid	ATC	chromosome segregation	183/6293	346/18723	8.03e-14	4.23e-12	183
GO:004802434	Thyroid	ATC	regulation of mRNA splicing, via spliceosome	70/6293	101/18723	2.29e-13	1.09e-11	70
GO:001907929	Thyroid	ATC	viral genome replication	78/6293	131/18723	9.92e-10	2.55e-08	78
GO:005079228	Thyroid	ATC	regulation of viral process	90/6293	164/18723	1.61e-08	3.23e-07	90
GO:004852424	Thyroid	ATC	positive regulation of viral process	44/6293	65/18723	2.00e-08	3.93e-07	44
GO:0006325110	Thyroid	ATC	chromatin organization	189/6293	409/18723	6.40e-08	1.13e-06	189
GO:190390028	Thyroid	ATC	regulation of viral life cycle	77/6293	148/18723	2.79e-06	3.21e-05	77
GO:004506926	Thyroid	ATC	regulation of viral genome replication	49/6293	85/18723	4.54e-06	4.97e-05	49
GO:004507022	Thyroid	ATC	positive regulation of viral genome replication	21/6293	30/18723	5.03e-05	3.96e-04	21
GO:000699714	Thyroid	ATC	nucleus organization	65/6293	133/18723	1.87e-04	1.26e-03	65
GO:004507110	Thyroid	ATC	negative regulation of viral genome replication	29/6293	56/18723	3.76e-03	1.64e-02	29
GO:000024515	Thyroid	ATC	spliceosomal complex assembly	38/6293	79/18723	5.28e-03	2.15e-02	38

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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

SRPK1

SNV

Missense_Mutation

c.1640N>T

p.Gly547Val

p.G547V

Q96SB4

protein_coding

deleterious(0)

probably_damaging(0.944)

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

SRPK1

SNV

Missense_Mutation

rs773631165

c.1756N>A

p.Tyr586Asn

p.Y586N

Q96SB4

protein_coding

deleterious(0.05)

probably_damaging(0.998)

TCGA-A7-A0DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SRPK1

SNV

Missense_Mutation

rs371124622

c.251G>A

p.Arg84Gln

p.R84Q

Q96SB4

protein_coding

deleterious(0.01)

benign(0.098)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SRPK1

SNV

Missense_Mutation

c.154G>C

p.Asp52His

p.D52H

Q96SB4

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SRPK1

SNV

Missense_Mutation

rs773631165

c.1756N>A

p.Tyr586Asn

p.Y586N

Q96SB4

protein_coding

deleterious(0.05)

probably_damaging(0.998)

TCGA-AR-A255-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

SRPK1

SNV

Missense_Mutation

novel

c.781G>C

p.Asp261His

p.D261H

Q96SB4

protein_coding

tolerated(0.09)

possibly_damaging(0.889)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

SRPK1

SNV

Missense_Mutation

c.1019A>G

p.Gln340Arg

p.Q340R

Q96SB4

protein_coding

tolerated(0.47)

benign(0.015)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SRPK1

SNV

Missense_Mutation

c.1462G>A

p.Ala488Thr

p.A488T

Q96SB4

protein_coding

deleterious(0.03)

probably_damaging(0.998)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

SRPK1

SNV

Missense_Mutation

novel

c.553N>G

p.Pro185Ala

p.P185A

Q96SB4

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-C5-A8YQ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

SRPK1

SNV

Missense_Mutation

rs749597130

c.1912N>G

p.Pro638Ala

p.P638A

Q96SB4

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AA-3833-01

Colorectum

colon adenocarcinoma

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
6732	SRPK1	KINASE, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		TAE-684	TAE-684
6732	SRPK1	KINASE, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		DOVITINIB	DOVITINIB
6732	SRPK1	KINASE, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		SNS-314	SNS-314
6732	SRPK1	KINASE, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		PF-562271	PF-00562271
6732	SRPK1	KINASE, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		ALISERTIB	ALISERTIB
6732	SRPK1	KINASE, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME	inhibitor	HESPERADIN	HESPERADIN	19035792
6732	SRPK1	KINASE, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		LINIFANIB	LINIFANIB
6732	SRPK1	KINASE, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		Sphinx
6732	SRPK1	KINASE, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		ZINC959121
6732	SRPK1	KINASE, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME	inhibitor	249565868

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