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: RBM19

Gene summary for RBM19

Gene summary.

Gene information	Species	Human
	Gene symbol	RBM19
	Gene ID	9904
	Gene name	RNA binding motif protein 19
	Gene Alias	Mrd1
	Cytomap	12q24.13-q24.21
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	Q9Y4C8

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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
9904	RBM19	LZE2T	Human	Esophagus	ESCC	1.45e-05	3.81e-01	0.082
9904	RBM19	LZE4T	Human	Esophagus	ESCC	4.89e-22	6.10e-01	0.0811
9904	RBM19	LZE7T	Human	Esophagus	ESCC	1.66e-10	3.81e-01	0.0667
9904	RBM19	LZE8T	Human	Esophagus	ESCC	5.20e-08	2.31e-01	0.067
9904	RBM19	LZE20T	Human	Esophagus	ESCC	4.59e-02	6.17e-02	0.0662
9904	RBM19	LZE24T	Human	Esophagus	ESCC	3.50e-05	1.01e-01	0.0596
9904	RBM19	P1T-E	Human	Esophagus	ESCC	5.65e-07	1.88e-01	0.0875
9904	RBM19	P2T-E	Human	Esophagus	ESCC	3.31e-30	5.81e-01	0.1177
9904	RBM19	P4T-E	Human	Esophagus	ESCC	1.42e-14	1.62e-01	0.1323
9904	RBM19	P5T-E	Human	Esophagus	ESCC	4.43e-12	1.78e-01	0.1327
9904	RBM19	P8T-E	Human	Esophagus	ESCC	6.05e-14	1.12e-01	0.0889
9904	RBM19	P9T-E	Human	Esophagus	ESCC	1.45e-10	2.86e-01	0.1131
9904	RBM19	P10T-E	Human	Esophagus	ESCC	9.77e-08	7.07e-02	0.116
9904	RBM19	P11T-E	Human	Esophagus	ESCC	4.61e-09	2.87e-01	0.1426
9904	RBM19	P12T-E	Human	Esophagus	ESCC	5.02e-12	2.03e-01	0.1122
9904	RBM19	P15T-E	Human	Esophagus	ESCC	5.88e-27	4.46e-01	0.1149
9904	RBM19	P16T-E	Human	Esophagus	ESCC	5.29e-23	2.53e-01	0.1153
9904	RBM19	P17T-E	Human	Esophagus	ESCC	5.62e-05	2.95e-01	0.1278
9904	RBM19	P19T-E	Human	Esophagus	ESCC	3.03e-02	2.15e-01	0.1662
9904	RBM19	P20T-E	Human	Esophagus	ESCC	3.85e-11	2.27e-01	0.1124

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0008380111	Esophagus	ESCC	RNA splicing	336/8552	434/18723	1.74e-42	3.67e-39	336
GO:0000375111	Esophagus	ESCC	RNA splicing, via transesterification reactions	248/8552	324/18723	3.05e-30	1.49e-27	248
GO:0000377111	Esophagus	ESCC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	244/8552	320/18723	2.52e-29	1.07e-26	244
GO:0000398111	Esophagus	ESCC	mRNA splicing, via spliceosome	244/8552	320/18723	2.52e-29	1.07e-26	244
GO:000838022	Liver	HCC	RNA splicing	313/7958	434/18723	1.36e-36	1.73e-33	313
GO:000037522	Liver	HCC	RNA splicing, via transesterification reactions	228/7958	324/18723	1.47e-24	4.06e-22	228
GO:000037722	Liver	HCC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	224/7958	320/18723	1.16e-23	2.62e-21	224
GO:000039822	Liver	HCC	mRNA splicing, via spliceosome	224/7958	320/18723	1.16e-23	2.62e-21	224
GO:000838020	Oral cavity	OSCC	RNA splicing	308/7305	434/18723	2.43e-42	7.70e-39	308
GO:000037519	Oral cavity	OSCC	RNA splicing, via transesterification reactions	225/7305	324/18723	5.20e-29	2.99e-26	225
GO:000037719	Oral cavity	OSCC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	221/7305	320/18723	5.50e-28	2.18e-25	221
GO:000039819	Oral cavity	OSCC	mRNA splicing, via spliceosome	221/7305	320/18723	5.50e-28	2.18e-25	221
GO:0008380110	Oral cavity	LP	RNA splicing	237/4623	434/18723	1.82e-41	3.79e-38	237
GO:0000375110	Oral cavity	LP	RNA splicing, via transesterification reactions	181/4623	324/18723	1.36e-33	1.70e-30	181
GO:0000377110	Oral cavity	LP	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	179/4623	320/18723	2.48e-33	2.22e-30	179
GO:0000398110	Oral cavity	LP	mRNA splicing, via spliceosome	179/4623	320/18723	2.48e-33	2.22e-30	179
GO:0008380113	Thyroid	PTC	RNA splicing	273/5968	434/18723	4.44e-41	1.40e-37	273
GO:0000375113	Thyroid	PTC	RNA splicing, via transesterification reactions	202/5968	324/18723	6.81e-30	3.91e-27	202
GO:0000377113	Thyroid	PTC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	199/5968	320/18723	2.96e-29	1.44e-26	199
GO:0000398113	Thyroid	PTC	mRNA splicing, via spliceosome	199/5968	320/18723	2.96e-29	1.44e-26	199

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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

RBM19

SNV

Missense_Mutation

novel

c.1744N>A

p.Ala582Thr

p.A582T

Q9Y4C8

protein_coding

deleterious(0.02)

benign(0.045)

TCGA-5T-A9QA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

RBM19

SNV

Missense_Mutation

c.2599N>G

p.Met867Val

p.M867V

Q9Y4C8

protein_coding

tolerated(0.1)

benign(0.02)

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

RBM19

SNV

Missense_Mutation

c.2509N>T

p.Arg837Trp

p.R837W

Q9Y4C8

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A0ER-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

RBM19

SNV

Missense_Mutation

rs774797332

c.671C>T

p.Ser224Leu

p.S224L

Q9Y4C8

protein_coding

tolerated(0.17)

benign(0)

TCGA-AR-A24X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RBM19

SNV

Missense_Mutation

novel

c.2442N>C

p.Lys814Asn

p.K814N

Q9Y4C8

protein_coding

tolerated(0.07)

benign(0.011)

TCGA-BH-A0BS-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

RBM19

SNV

Missense_Mutation

c.2628N>A

p.Phe876Leu

p.F876L

Q9Y4C8

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C8-A1HI-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

RBM19

SNV

Missense_Mutation

novel

c.1559N>C

p.Gly520Ala

p.G520A

Q9Y4C8

protein_coding

deleterious(0.04)

probably_damaging(0.925)

TCGA-E9-A5FL-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RBM19

insertion

Nonsense_Mutation

novel

c.1016_1017insGCCCTGACTCCTCTTCATTGCAGG

p.Asp339delinsGluProTerLeuLeuPheIleAlaGly

p.D339delinsEP*LLFIAG

Q9Y4C8

protein_coding

TCGA-A8-A09N-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

RBM19

SNV

Missense_Mutation

novel

c.2395N>A

p.Val799Met

p.V799M

Q9Y4C8

protein_coding

tolerated(0.06)

probably_damaging(0.913)

TCGA-C5-A8XK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RBM19

SNV

Missense_Mutation

rs763155552

c.1006N>G

p.Ile336Val

p.I336V

Q9Y4C8

protein_coding

tolerated(1)

benign(0)

TCGA-Q1-A5R2-01

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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