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: PRPF4B

Gene summary for PRPF4B

Gene summary.

Gene information	Species	Human
	Gene symbol	PRPF4B
	Gene ID	8899
	Gene name	pre-mRNA processing factor 4B
	Gene Alias	PR4H
	Cytomap	6p25.2
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	A0A024QZY5

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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
8899	PRPF4B	CA_HPV_1	Human	Cervix	CC	3.22e-07	-9.37e-03	0.0264
8899	PRPF4B	CA_HPV_2	Human	Cervix	CC	6.36e-03	2.99e-01	0.0391
8899	PRPF4B	CCI_2	Human	Cervix	CC	6.64e-15	1.18e+00	0.5249
8899	PRPF4B	CCII_1	Human	Cervix	CC	3.37e-05	-4.57e-01	0.3249
8899	PRPF4B	Tumor	Human	Cervix	CC	1.92e-05	-3.36e-01	0.1241
8899	PRPF4B	sample3	Human	Cervix	CC	2.67e-05	-2.78e-01	0.1387
8899	PRPF4B	L1	Human	Cervix	CC	1.61e-03	-2.07e-01	0.0802
8899	PRPF4B	T3	Human	Cervix	CC	1.15e-05	-2.67e-01	0.1389
8899	PRPF4B	HTA11_3410_2000001011	Human	Colorectum	AD	8.07e-29	-7.09e-01	0.0155
8899	PRPF4B	HTA11_2487_2000001011	Human	Colorectum	SER	1.29e-10	-5.98e-01	-0.1808
8899	PRPF4B	HTA11_2951_2000001011	Human	Colorectum	AD	2.22e-03	-7.02e-01	0.0216
8899	PRPF4B	HTA11_1938_2000001011	Human	Colorectum	AD	2.34e-04	-4.71e-01	-0.0811
8899	PRPF4B	HTA11_78_2000001011	Human	Colorectum	AD	1.03e-08	-4.78e-01	-0.1088
8899	PRPF4B	HTA11_347_2000001011	Human	Colorectum	AD	3.92e-04	-2.50e-01	-0.1954
8899	PRPF4B	HTA11_2112_2000001011	Human	Colorectum	SER	1.28e-02	-6.95e-01	-0.2196
8899	PRPF4B	HTA11_3361_2000001011	Human	Colorectum	AD	4.02e-09	-6.12e-01	-0.1207
8899	PRPF4B	HTA11_83_2000001011	Human	Colorectum	SER	6.02e-06	-5.38e-01	-0.1526
8899	PRPF4B	HTA11_696_2000001011	Human	Colorectum	AD	2.37e-15	-5.41e-01	-0.1464
8899	PRPF4B	HTA11_866_2000001011	Human	Colorectum	AD	2.27e-10	-4.57e-01	-0.1001
8899	PRPF4B	HTA11_1391_2000001011	Human	Colorectum	AD	1.05e-09	-4.84e-01	-0.059

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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
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:000838010	Cervix	CC	RNA splicing	76/2311	434/18723	9.79e-04	8.19e-03	76
GO:000037710	Cervix	CC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	55/2311	320/18723	6.71e-03	3.70e-02	55
GO:000039810	Cervix	CC	mRNA splicing, via spliceosome	55/2311	320/18723	6.71e-03	3.70e-02	55
GO:000037510	Cervix	CC	RNA splicing, via transesterification reactions	55/2311	324/18723	8.61e-03	4.44e-02	55
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:00083801	Colorectum	SER	RNA splicing	123/2897	434/18723	3.84e-12	8.41e-10	123
GO:00003751	Colorectum	SER	RNA splicing, via transesterification reactions	90/2897	324/18723	8.68e-09	7.50e-07	90
GO:00003771	Colorectum	SER	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	89/2897	320/18723	9.82e-09	8.14e-07	89
GO:00003981	Colorectum	SER	mRNA splicing, via spliceosome	89/2897	320/18723	9.82e-09	8.14e-07	89
GO:00083802	Colorectum	MSS	RNA splicing	159/3467	434/18723	1.75e-19	1.22e-16	159
GO:00003772	Colorectum	MSS	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	121/3467	320/18723	2.52e-16	8.27e-14	121
GO:00003982	Colorectum	MSS	mRNA splicing, via spliceosome	121/3467	320/18723	2.52e-16	8.27e-14	121
GO:00003752	Colorectum	MSS	RNA splicing, via transesterification reactions	122/3467	324/18723	2.75e-16	8.58e-14	122
GO:00083804	Colorectum	FAP	RNA splicing	108/2622	434/18723	7.90e-10	1.86e-07	108
GO:00003754	Colorectum	FAP	RNA splicing, via transesterification reactions	84/2622	324/18723	8.06e-09	1.10e-06	84
GO:00003774	Colorectum	FAP	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	83/2622	320/18723	9.66e-09	1.23e-06	83
GO:00003984	Colorectum	FAP	mRNA splicing, via spliceosome	83/2622	320/18723	9.66e-09	1.23e-06	83

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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

PRPF4B

SNV

Missense_Mutation

c.260N>T

p.Ser87Phe

p.S87F

Q13523

protein_coding

deleterious_low_confidence(0.01)

benign(0.121)

TCGA-A1-A0SH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

PRPF4B

SNV

Missense_Mutation

rs753689645

c.1988N>G

p.Asn663Ser

p.N663S

Q13523

protein_coding

tolerated(0.28)

benign(0.039)

TCGA-A8-A096-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRPF4B

SNV

Missense_Mutation

c.1872G>C

p.Gln624His

p.Q624H

Q13523

protein_coding

tolerated(0.06)

probably_damaging(0.948)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRPF4B

SNV

Missense_Mutation

c.25N>A

p.Leu9Ile

p.L9I

Q13523

protein_coding

deleterious_low_confidence(0)

benign(0.007)

TCGA-AO-A0J4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PRPF4B

SNV

Missense_Mutation

c.710N>C

p.Arg237Thr

p.R237T

Q13523

protein_coding

deleterious_low_confidence(0)

benign(0.007)

TCGA-AO-A124-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PRPF4B

SNV

Missense_Mutation

c.361N>C

p.Asp121His

p.D121H

Q13523

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.67)

TCGA-BH-A1FU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PRPF4B

SNV

Missense_Mutation

c.155N>A

p.Ser52Asn

p.S52N

Q13523

protein_coding

tolerated_low_confidence(0.39)

benign(0.001)

TCGA-EW-A1IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

aromasin

PRPF4B

SNV

Missense_Mutation

c.2578A>G

p.Ile860Val

p.I860V

Q13523

protein_coding

tolerated(0.06)

probably_damaging(0.956)

TCGA-EW-A1P6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PRPF4B

SNV

Missense_Mutation

rs768895871

c.1391G>A

p.Arg464Lys

p.R464K

Q13523

protein_coding

tolerated(0.06)

possibly_damaging(0.745)

TCGA-EW-A1PB-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PRPF4B

SNV

Missense_Mutation

novel

c.1948C>T

p.Arg650Trp

p.R650W

Q13523

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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