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: PRPF19

Gene summary for PRPF19

Gene summary.

Gene information	Species	Human
	Gene symbol	PRPF19
	Gene ID	27339
	Gene name	pre-mRNA processing factor 19
	Gene Alias	NMP200
	Cytomap	11q12.2
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	Q9UMS4

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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
27339	PRPF19	HTA11_2487_2000001011	Human	Colorectum	SER	6.66e-03	2.55e-01	-0.1808
27339	PRPF19	HTA11_1938_2000001011	Human	Colorectum	AD	2.44e-10	5.57e-01	-0.0811
27339	PRPF19	HTA11_347_2000001011	Human	Colorectum	AD	7.67e-09	3.11e-01	-0.1954
27339	PRPF19	HTA11_3361_2000001011	Human	Colorectum	AD	4.70e-04	3.35e-01	-0.1207
27339	PRPF19	HTA11_696_2000001011	Human	Colorectum	AD	8.20e-06	2.95e-01	-0.1464
27339	PRPF19	HTA11_866_2000001011	Human	Colorectum	AD	3.50e-03	1.89e-01	-0.1001
27339	PRPF19	HTA11_1391_2000001011	Human	Colorectum	AD	2.99e-08	4.70e-01	-0.059
27339	PRPF19	HTA11_2992_2000001011	Human	Colorectum	SER	1.71e-02	4.33e-01	-0.1706
27339	PRPF19	HTA11_5216_2000001011	Human	Colorectum	SER	7.12e-03	3.22e-01	-0.1462
27339	PRPF19	HTA11_546_2000001011	Human	Colorectum	AD	3.54e-06	3.49e-01	-0.0842
27339	PRPF19	HTA11_866_3004761011	Human	Colorectum	AD	4.98e-21	6.04e-01	0.096
27339	PRPF19	HTA11_4255_2000001011	Human	Colorectum	SER	7.94e-05	5.15e-01	0.0446
27339	PRPF19	HTA11_8622_2000001021	Human	Colorectum	SER	2.61e-06	5.32e-01	0.0528
27339	PRPF19	HTA11_7663_2000001011	Human	Colorectum	SER	6.59e-06	5.13e-01	0.0131
27339	PRPF19	HTA11_6801_2000001011	Human	Colorectum	SER	1.93e-02	5.29e-01	0.0171
27339	PRPF19	HTA11_10711_2000001011	Human	Colorectum	AD	2.00e-04	3.44e-01	0.0338
27339	PRPF19	HTA11_7696_3000711011	Human	Colorectum	AD	6.02e-10	3.54e-01	0.0674
27339	PRPF19	HTA11_7469_2000001011	Human	Colorectum	AD	4.24e-02	4.00e-01	-0.0124
27339	PRPF19	HTA11_6818_2000001021	Human	Colorectum	AD	8.12e-07	4.16e-01	0.0588
27339	PRPF19	HTA11_99999970781_79442	Human	Colorectum	MSS	3.62e-22	5.92e-01	0.294

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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
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
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:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0043484	Colorectum	AD	regulation of RNA splicing	70/3918	148/18723	6.47e-13	1.16e-10	70
GO:0022618	Colorectum	AD	ribonucleoprotein complex assembly	92/3918	220/18723	1.49e-12	2.60e-10	92
GO:0071826	Colorectum	AD	ribonucleoprotein complex subunit organization	94/3918	227/18723	1.70e-12	2.87e-10	94
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:0022613	Colorectum	AD	ribonucleoprotein complex biogenesis	151/3918	463/18723	1.96e-09	1.39e-07	151
GO:0000209	Colorectum	AD	protein polyubiquitination	78/3918	236/18723	8.71e-06	2.06e-04	78
GO:0000245	Colorectum	AD	spliceosomal complex assembly	33/3918	79/18723	2.15e-05	4.33e-04	33
GO:1903313	Colorectum	AD	positive regulation of mRNA metabolic process	44/3918	118/18723	3.20e-05	5.87e-04	44
GO:0033120	Colorectum	AD	positive regulation of RNA splicing	19/3918	37/18723	4.08e-05	7.26e-04	19
GO:0010720	Colorectum	AD	positive regulation of cell development	87/3918	298/18723	4.17e-04	4.71e-03	87
GO:0048026	Colorectum	AD	positive regulation of mRNA splicing, via spliceosome	12/3918	22/18723	5.38e-04	5.74e-03	12
GO:0050767	Colorectum	AD	regulation of neurogenesis	99/3918	364/18723	2.35e-03	1.82e-02	99
GO:0070534	Colorectum	AD	protein K63-linked ubiquitination	20/3918	56/18723	7.57e-03	4.58e-02	20

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa03040	Colorectum	AD	Spliceosome	73/2092	217/8465	1.73e-03	9.68e-03	6.18e-03	73
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa030401	Colorectum	AD	Spliceosome	73/2092	217/8465	1.73e-03	9.68e-03	6.18e-03	73
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa030402	Colorectum	MSS	Spliceosome	66/1875	217/8465	2.58e-03	1.27e-02	7.81e-03	66
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa030403	Colorectum	MSS	Spliceosome	66/1875	217/8465	2.58e-03	1.27e-02	7.81e-03	66
hsa030404	Colorectum	MSI-H	Spliceosome	37/797	217/8465	2.49e-04	3.23e-03	2.70e-03	37
hsa030405	Colorectum	MSI-H	Spliceosome	37/797	217/8465	2.49e-04	3.23e-03	2.70e-03	37
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0304027	Esophagus	ESCC	Spliceosome	128/4205	217/8465	3.31e-03	8.79e-03	4.50e-03	128
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0304037	Esophagus	ESCC	Spliceosome	128/4205	217/8465	3.31e-03	8.79e-03	4.50e-03	128
hsa030407	Liver	Cirrhotic	Spliceosome	102/2530	217/8465	5.69e-08	9.47e-07	5.84e-07	102
hsa0412021	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0304012	Liver	Cirrhotic	Spliceosome	102/2530	217/8465	5.69e-08	9.47e-07	5.84e-07	102
hsa0412031	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72

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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

PRPF19

SNV

Missense_Mutation

rs201780573

c.859N>C

p.Thr287Pro

p.T287P

Q9UMS4

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PRPF19

SNV

Missense_Mutation

rs201780573

c.859N>C

p.Thr287Pro

p.T287P

Q9UMS4

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-A8-A079-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

PRPF19

SNV

Missense_Mutation

rs201780573

c.859N>C

p.Thr287Pro

p.T287P

Q9UMS4

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

PRPF19

SNV

Missense_Mutation

rs201780573

c.859A>C

p.Thr287Pro

p.T287P

Q9UMS4

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-AO-A12H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PRPF19

SNV

Missense_Mutation

rs201780573

c.859N>C

p.Thr287Pro

p.T287P

Q9UMS4

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-B6-A0WS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PRPF19

SNV

Missense_Mutation

novel

c.586N>C

p.Glu196Gln

p.E196Q

Q9UMS4

protein_coding

tolerated(0.08)

benign(0.265)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PRPF19

SNV

Missense_Mutation

rs201780573

c.859N>C

p.Thr287Pro

p.T287P

Q9UMS4

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-BH-A0B7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PRPF19

SNV

Missense_Mutation

rs201780573

c.859N>C

p.Thr287Pro

p.T287P

Q9UMS4

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

PRPF19

SNV

Missense_Mutation

rs201780573

c.859A>C

p.Thr287Pro

p.T287P

Q9UMS4

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-BH-A0C7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PRPF19

SNV

Missense_Mutation

rs201780573

c.859A>C

p.Thr287Pro

p.T287P

Q9UMS4

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-BH-A0DE-01

Breast

breast invasive 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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