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: DUSP19

Gene summary for DUSP19

Gene summary.

Gene information	Species	Human
	Gene symbol	DUSP19
	Gene ID	142679
	Gene name	dual specificity phosphatase 19
	Gene Alias	DUSP17
	Cytomap	2q32.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q8WTR2

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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
142679	DUSP19	HCC1_Meng	Human	Liver	HCC	2.67e-03	2.62e-02	0.0246
142679	DUSP19	HCC1	Human	Liver	HCC	1.33e-05	6.10e-01	0.5336
142679	DUSP19	HCC2	Human	Liver	HCC	2.11e-13	1.74e+00	0.5341
142679	DUSP19	HCC5	Human	Liver	HCC	2.57e-02	1.83e-01	0.4932
142679	DUSP19	S015	Human	Liver	HCC	2.18e-03	1.34e-01	0.2375

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:001056322	Liver	HCC	negative regulation of phosphorus metabolic process	259/7958	442/18723	4.29e-12	1.92e-10	259
GO:004593622	Liver	HCC	negative regulation of phosphate metabolic process	258/7958	441/18723	6.00e-12	2.60e-10	258
GO:004232622	Liver	HCC	negative regulation of phosphorylation	227/7958	385/18723	3.98e-11	1.52e-09	227
GO:005134822	Liver	HCC	negative regulation of transferase activity	166/7958	268/18723	8.97e-11	3.18e-09	166
GO:003367322	Liver	HCC	negative regulation of kinase activity	144/7958	237/18723	9.76e-09	2.45e-07	144
GO:000193322	Liver	HCC	negative regulation of protein phosphorylation	196/7958	342/18723	1.95e-08	4.63e-07	196
GO:001631121	Liver	HCC	dephosphorylation	230/7958	417/18723	1.00e-07	1.96e-06	230
GO:000647021	Liver	HCC	protein dephosphorylation	162/7958	281/18723	1.91e-07	3.46e-06	162
GO:000646912	Liver	HCC	negative regulation of protein kinase activity	126/7958	212/18723	4.55e-07	7.49e-06	126
GO:003109822	Liver	HCC	stress-activated protein kinase signaling cascade	138/7958	247/18723	1.43e-05	1.57e-04	138
GO:005140322	Liver	HCC	stress-activated MAPK cascade	134/7958	239/18723	1.50e-05	1.64e-04	134
GO:007190021	Liver	HCC	regulation of protein serine/threonine kinase activity	189/7958	359/18723	5.97e-05	5.47e-04	189
GO:00434097	Liver	HCC	negative regulation of MAPK cascade	98/7958	180/18723	7.88e-04	4.74e-03	98
GO:007030222	Liver	HCC	regulation of stress-activated protein kinase signaling cascade	105/7958	195/18723	8.79e-04	5.20e-03	105
GO:003287312	Liver	HCC	negative regulation of stress-activated MAPK cascade	33/7958	51/18723	1.13e-03	6.44e-03	33
GO:007030312	Liver	HCC	negative regulation of stress-activated protein kinase signaling cascade	33/7958	51/18723	1.13e-03	6.44e-03	33
GO:004586021	Liver	HCC	positive regulation of protein kinase activity	194/7958	386/18723	1.16e-03	6.54e-03	194
GO:003367411	Liver	HCC	positive regulation of kinase activity	230/7958	467/18723	1.72e-03	8.95e-03	230
GO:003287222	Liver	HCC	regulation of stress-activated MAPK cascade	102/7958	192/18723	1.86e-03	9.49e-03	102
GO:000725412	Liver	HCC	JNK cascade	89/7958	167/18723	3.09e-03	1.44e-02	89

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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

DUSP19

SNV

Missense_Mutation

novel

c.185C>T

p.Ser62Leu

p.S62L

Q8WTR2

protein_coding

tolerated(0.43)

benign(0)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

DUSP19

SNV

Missense_Mutation

c.189N>A

p.Asp63Glu

p.D63E

Q8WTR2

protein_coding

deleterious(0.02)

possibly_damaging(0.866)

TCGA-A2-A25B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

DUSP19

SNV

Missense_Mutation

novel

c.223N>A

p.Leu75Ile

p.L75I

Q8WTR2

protein_coding

deleterious(0.01)

probably_damaging(0.951)

TCGA-AC-A6IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DUSP19

SNV

Missense_Mutation

c.109N>T

p.Asp37Tyr

p.D37Y

Q8WTR2

protein_coding

deleterious(0.01)

possibly_damaging(0.526)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DUSP19

SNV

Missense_Mutation

novel

c.286N>A

p.Leu96Ile

p.L96I

Q8WTR2

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DUSP19

SNV

Missense_Mutation

c.23N>C

p.Ile8Thr

p.I8T

Q8WTR2

protein_coding

deleterious(0)

probably_damaging(0.917)

TCGA-E9-A226-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

DUSP19

SNV

Missense_Mutation

novel

c.650C>T

p.Ser217Leu

p.S217L

Q8WTR2

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-S3-AA15-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DUSP19

SNV

Missense_Mutation

c.592C>T

p.Arg198Cys

p.R198C

Q8WTR2

protein_coding

deleterious(0.02)

benign(0.022)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

DUSP19

SNV

Missense_Mutation

novel

c.608N>A

p.Gly203Asp

p.G203D

Q8WTR2

protein_coding

tolerated_low_confidence(0.66)

benign(0.09)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

DUSP19

SNV

Missense_Mutation

novel

c.339N>T

p.Lys113Asn

p.K113N

Q8WTR2

protein_coding

deleterious(0.01)

possibly_damaging(0.566)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<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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