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: SRSF3

Gene summary for SRSF3

Gene summary.

Gene information	Species	Human
	Gene symbol	SRSF3
	Gene ID	6428
	Gene name	serine and arginine rich splicing factor 3
	Gene Alias	SFRS3
	Cytomap	6p21.31-p21.2
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	B2R6F3

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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
6428	SRSF3	GSM4909277	Human	Breast	Precancer	4.10e-03	5.64e-01	0.0177
6428	SRSF3	GSM4909281	Human	Breast	IDC	6.05e-03	2.42e-01	0.21
6428	SRSF3	GSM4909282	Human	Breast	IDC	7.96e-08	3.41e-01	-0.0288
6428	SRSF3	GSM4909285	Human	Breast	IDC	3.39e-08	2.77e-01	0.21
6428	SRSF3	GSM4909286	Human	Breast	IDC	7.59e-05	-5.75e-02	0.1081
6428	SRSF3	GSM4909293	Human	Breast	IDC	1.22e-02	1.80e-01	0.1581
6428	SRSF3	GSM4909294	Human	Breast	IDC	4.72e-04	-5.21e-02	0.2022
6428	SRSF3	GSM4909296	Human	Breast	IDC	1.84e-16	-5.00e-01	0.1524
6428	SRSF3	GSM4909297	Human	Breast	IDC	1.13e-33	2.35e-01	0.1517
6428	SRSF3	GSM4909301	Human	Breast	IDC	1.60e-02	-3.37e-01	0.1577
6428	SRSF3	GSM4909302	Human	Breast	IDC	1.22e-02	-3.72e-01	0.1545
6428	SRSF3	GSM4909308	Human	Breast	IDC	3.07e-04	2.19e-01	0.158
6428	SRSF3	GSM4909311	Human	Breast	IDC	8.34e-44	-6.68e-01	0.1534
6428	SRSF3	GSM4909312	Human	Breast	IDC	2.77e-08	-1.82e-02	0.1552
6428	SRSF3	GSM4909317	Human	Breast	IDC	2.46e-02	2.29e-01	0.1355
6428	SRSF3	GSM4909319	Human	Breast	IDC	4.01e-53	-6.40e-01	0.1563
6428	SRSF3	GSM4909320	Human	Breast	IDC	1.19e-12	-7.19e-01	0.1575
6428	SRSF3	GSM4909321	Human	Breast	IDC	2.71e-13	-2.68e-02	0.1559
6428	SRSF3	brca2	Human	Breast	Precancer	8.83e-03	1.45e-01	-0.024
6428	SRSF3	brca3	Human	Breast	Precancer	5.98e-03	1.90e-01	-0.0263

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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:00083809	Breast	Precancer	RNA splicing	65/1080	434/18723	1.27e-12	2.53e-10	65
GO:00434849	Breast	Precancer	regulation of RNA splicing	34/1080	148/18723	2.66e-12	4.75e-10	34
GO:00003759	Breast	Precancer	RNA splicing, via transesterification reactions	52/1080	324/18723	1.74e-11	2.22e-09	52
GO:00003779	Breast	Precancer	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00003989	Breast	Precancer	mRNA splicing, via spliceosome	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00480249	Breast	Precancer	regulation of mRNA splicing, via spliceosome	22/1080	101/18723	5.29e-08	3.18e-06	22
GO:19033118	Breast	Precancer	regulation of mRNA metabolic process	38/1080	288/18723	1.63e-06	5.97e-05	38
GO:00506848	Breast	Precancer	regulation of mRNA processing	23/1080	137/18723	3.49e-06	1.13e-04	23
GO:00064039	Breast	Precancer	RNA localization	23/1080	201/18723	1.34e-03	1.41e-02	23
GO:19908303	Breast	Precancer	cellular response to leukemia inhibitory factor	13/1080	94/18723	2.83e-03	2.49e-02	13
GO:19908233	Breast	Precancer	response to leukemia inhibitory factor	13/1080	95/18723	3.11e-03	2.64e-02	13
GO:000838014	Breast	IDC	RNA splicing	73/1434	434/18723	1.27e-10	1.57e-08	73
GO:004348414	Breast	IDC	regulation of RNA splicing	36/1434	148/18723	3.32e-10	3.77e-08	36
GO:000037514	Breast	IDC	RNA splicing, via transesterification reactions	58/1434	324/18723	9.44e-10	9.58e-08	58
GO:000037714	Breast	IDC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	57/1434	320/18723	1.60e-09	1.49e-07	57
GO:000039814	Breast	IDC	mRNA splicing, via spliceosome	57/1434	320/18723	1.60e-09	1.49e-07	57
GO:004802414	Breast	IDC	regulation of mRNA splicing, via spliceosome	23/1434	101/18723	1.74e-06	7.28e-05	23
GO:005068413	Breast	IDC	regulation of mRNA processing	24/1434	137/18723	1.09e-04	2.04e-03	24
GO:190331113	Breast	IDC	regulation of mRNA metabolic process	40/1434	288/18723	1.79e-04	3.01e-03	40
GO:000640313	Breast	IDC	RNA localization	27/1434	201/18723	3.04e-03	2.60e-02	27

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501416	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa030408	Breast	Precancer	Spliceosome	39/684	217/8465	1.44e-06	2.27e-05	1.74e-05	39
hsa0501417	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0304013	Breast	Precancer	Spliceosome	39/684	217/8465	1.44e-06	2.27e-05	1.74e-05	39
hsa0501423	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0304023	Breast	IDC	Spliceosome	40/867	217/8465	1.53e-04	1.42e-03	1.06e-03	40
hsa0501433	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0304033	Breast	IDC	Spliceosome	40/867	217/8465	1.53e-04	1.42e-03	1.06e-03	40
hsa0501443	Breast	DCIS	Amyotrophic lateral sclerosis	101/846	364/8465	7.14e-23	2.88e-21	2.12e-21	101
hsa0304043	Breast	DCIS	Spliceosome	40/846	217/8465	8.97e-05	8.52e-04	6.28e-04	40
hsa0501453	Breast	DCIS	Amyotrophic lateral sclerosis	101/846	364/8465	7.14e-23	2.88e-21	2.12e-21	101
hsa0304053	Breast	DCIS	Spliceosome	40/846	217/8465	8.97e-05	8.52e-04	6.28e-04	40
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
hsa0501444	Cervix	N_HPV	Amyotrophic lateral sclerosis	41/349	364/8465	3.11e-09	1.06e-07	8.26e-08	41
hsa0501454	Cervix	N_HPV	Amyotrophic lateral sclerosis	41/349	364/8465	3.11e-09	1.06e-07	8.26e-08	41
hsa05014	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa03040	Colorectum	AD	Spliceosome	73/2092	217/8465	1.73e-03	9.68e-03	6.18e-03	73
hsa050141	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa030401	Colorectum	AD	Spliceosome	73/2092	217/8465	1.73e-03	9.68e-03	6.18e-03	73

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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

SRSF3

SNV

Missense_Mutation

c.313C>T

p.Arg105Cys

p.R105C

P84103

protein_coding

deleterious(0)

possibly_damaging(0.586)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SRSF3

insertion

Frame_Shift_Ins

novel

c.268_269insCT

p.Arg90ProfsTer104

p.R90Pfs*104

P84103

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

SRSF3

insertion

Frame_Shift_Ins

novel

c.269_270insGAGTGCAATGGCACAATCT

p.Gly91SerfsTer19

p.G91Sfs*19

P84103

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

SRSF3

SNV

Missense_Mutation

novel

c.404N>A

p.Arg135Lys

p.R135K

P84103

protein_coding

deleterious_low_confidence(0.02)

benign(0.267)

TCGA-C5-A8ZZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unspecific

Cisplatin

SRSF3

SNV

Missense_Mutation

novel

c.160N>C

p.Glu54Gln

p.E54Q

P84103

protein_coding

deleterious(0.01)

probably_damaging(0.997)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

SRSF3

SNV

Missense_Mutation

c.257N>T

p.Arg86Ile

p.R86I

P84103

protein_coding

deleterious(0)

probably_damaging(0.944)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SRSF3

SNV

Missense_Mutation

novel

c.68A>T

p.Lys23Met

p.K23M

P84103

protein_coding

deleterious(0.01)

possibly_damaging(0.824)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

SRSF3

SNV

Missense_Mutation

novel

c.446N>A

p.Arg149Gln

p.R149Q

P84103

protein_coding

tolerated_low_confidence(0.29)

possibly_damaging(0.614)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

SRSF3

SNV

Missense_Mutation

c.304N>T

p.Asp102Tyr

p.D102Y

P84103

protein_coding

deleterious(0.02)

possibly_damaging(0.675)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SRSF3

SNV

Missense_Mutation

c.76T>G

p.Leu26Val

p.L26V

P84103

protein_coding

deleterious(0.03)

probably_damaging(0.953)

TCGA-AP-A054-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

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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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