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: USP19

Gene summary for USP19

Gene summary.

Gene information	Species	Human
	Gene symbol	USP19
	Gene ID	10869
	Gene name	ubiquitin specific peptidase 19
	Gene Alias	ZMYND9
	Cytomap	3p21.31
	Gene Type	protein-coding
	GO ID	GO:0001666
	UniProtAcc	O94966

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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
10869	USP19	HCC1_Meng	Human	Liver	HCC	9.91e-27	3.29e-02	0.0246
10869	USP19	HCC2	Human	Liver	HCC	5.07e-09	2.13e+00	0.5341
10869	USP19	S014	Human	Liver	HCC	1.25e-19	5.56e-01	0.2254
10869	USP19	S015	Human	Liver	HCC	8.77e-11	4.37e-01	0.2375
10869	USP19	S016	Human	Liver	HCC	5.08e-19	6.17e-01	0.2243
10869	USP19	S027	Human	Liver	HCC	1.00e-06	6.12e-01	0.2446
10869	USP19	S028	Human	Liver	HCC	2.06e-25	7.44e-01	0.2503
10869	USP19	S029	Human	Liver	HCC	1.62e-20	7.56e-01	0.2581

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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:001049822	Liver	HCC	proteasomal protein catabolic process	351/7958	490/18723	6.92e-40	1.46e-36	351
GO:004316122	Liver	HCC	proteasome-mediated ubiquitin-dependent protein catabolic process	299/7958	412/18723	7.82e-36	8.27e-33	299
GO:004217622	Liver	HCC	regulation of protein catabolic process	267/7958	391/18723	2.45e-25	7.38e-23	267
GO:003497612	Liver	HCC	response to endoplasmic reticulum stress	189/7958	256/18723	1.43e-24	4.06e-22	189
GO:003164722	Liver	HCC	regulation of protein stability	211/7958	298/18723	2.29e-23	5.01e-21	211
GO:190336222	Liver	HCC	regulation of cellular protein catabolic process	182/7958	255/18723	5.91e-21	8.52e-19	182
GO:190305022	Liver	HCC	regulation of proteolysis involved in cellular protein catabolic process	157/7958	221/18723	5.93e-18	6.83e-16	157
GO:005082122	Liver	HCC	protein stabilization	139/7958	191/18723	1.61e-17	1.71e-15	139
GO:003650311	Liver	HCC	ERAD pathway	88/7958	107/18723	2.87e-17	2.85e-15	88
GO:006113622	Liver	HCC	regulation of proteasomal protein catabolic process	134/7958	187/18723	5.03e-16	4.09e-14	134
GO:00304331	Liver	HCC	ubiquitin-dependent ERAD pathway	72/7958	85/18723	9.78e-16	7.47e-14	72
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:000989522	Liver	HCC	negative regulation of catabolic process	196/7958	320/18723	7.98e-12	3.35e-10	196
GO:003133022	Liver	HCC	negative regulation of cellular catabolic process	164/7958	262/18723	3.52e-11	1.35e-09	164
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:190589712	Liver	HCC	regulation of response to endoplasmic reticulum stress	62/7958	82/18723	1.06e-09	3.23e-08	62
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

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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

USP19

SNV

Missense_Mutation

novel

c.2807N>A

p.Pro936His

p.P936H

O94966

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

USP19

SNV

Missense_Mutation

c.316N>G

p.His106Asp

p.H106D

O94966

protein_coding

tolerated_low_confidence(0.44)

benign(0.005)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP19

SNV

Missense_Mutation

c.2291C>A

p.Ser764Tyr

p.S764Y

O94966

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0H5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

USP19

SNV

Missense_Mutation

c.3950N>G

p.Ser1317Cys

p.S1317C

O94966

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

USP19

insertion

Frame_Shift_Ins

novel

c.2341_2342insTACTT

p.Gln781LeufsTer24

p.Q781Lfs*24

O94966

protein_coding

TCGA-A8-A08P-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

USP19

SNV

Missense_Mutation

novel

c.3440C>T

p.Pro1147Leu

p.P1147L

O94966

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

USP19

SNV

Missense_Mutation

novel

c.164N>T

p.Pro55Leu

p.P55L

O94966

protein_coding

tolerated_low_confidence(0.38)

benign(0)

TCGA-DS-A1OD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

USP19

SNV

Missense_Mutation

c.3838N>G

p.Gln1280Glu

p.Q1280E

O94966

protein_coding

deleterious(0.03)

probably_damaging(0.994)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

USP19

SNV

Missense_Mutation

c.2460N>C

p.Gln820His

p.Q820H

O94966

protein_coding

tolerated(0.53)

benign(0.006)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

USP19

SNV

Missense_Mutation

c.3871G>A

p.Asp1291Asn

p.D1291N

O94966

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-Q1-A73O-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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