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: USP49

Gene summary for USP49

Gene summary.

Gene information	Species	Human
	Gene symbol	USP49
	Gene ID	25862
	Gene name	ubiquitin specific peptidase 49
	Gene Alias	USP49
	Cytomap	6p21.1
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	Q70CQ1

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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
25862	USP49	HCC1	Human	Liver	HCC	3.32e-17	2.75e+00	0.5336
25862	USP49	HCC2	Human	Liver	HCC	4.34e-28	2.80e+00	0.5341
25862	USP49	HCC5	Human	Liver	HCC	8.75e-21	1.97e+00	0.4932
25862	USP49	RNA-P25T1-P25T1-1	Human	Lung	AIS	8.87e-03	2.38e-01	-0.2116
25862	USP49	RNA-P6T1-P6T1-1	Human	Lung	MIAC	3.00e-03	5.97e-01	-0.0238
25862	USP49	RNA-P6T1-P6T1-3	Human	Lung	MIAC	3.47e-02	5.93e-01	-0.0296
25862	USP49	RNA-P6T2-P6T2-3	Human	Lung	IAC	1.30e-03	1.87e-01	-0.013

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma

∗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: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:001657021	Liver	HCC	histone modification	283/7958	463/18723	2.68e-16	2.33e-14	283
GO:00706461	Liver	HCC	protein modification by small protein removal	91/7958	157/18723	6.50e-05	5.92e-04	91
GO:00165791	Liver	HCC	protein deubiquitination	78/7958	139/18723	8.13e-04	4.87e-03	78
GO:0016578	Liver	HCC	histone deubiquitination	17/7958	23/18723	2.28e-03	1.13e-02	17
GO:00165704	Lung	IAC	histone modification	93/2061	463/18723	5.41e-09	8.03e-07	93
GO:00083808	Lung	IAC	RNA splicing	75/2061	434/18723	4.89e-05	1.12e-03	75
GO:00003778	Lung	IAC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	52/2061	320/18723	2.64e-03	2.44e-02	52
GO:00003988	Lung	IAC	mRNA splicing, via spliceosome	52/2061	320/18723	2.64e-03	2.44e-02	52
GO:00003758	Lung	IAC	RNA splicing, via transesterification reactions	52/2061	324/18723	3.43e-03	2.93e-02	52
GO:001657012	Lung	AIS	histone modification	81/1849	463/18723	2.30e-07	2.16e-05	81
GO:000838013	Lung	AIS	RNA splicing	68/1849	434/18723	8.50e-05	2.11e-03	68
GO:000037713	Lung	AIS	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	49/1849	320/18723	1.30e-03	1.63e-02	49
GO:000039813	Lung	AIS	mRNA splicing, via spliceosome	49/1849	320/18723	1.30e-03	1.63e-02	49
GO:000037513	Lung	AIS	RNA splicing, via transesterification reactions	49/1849	324/18723	1.69e-03	1.93e-02	49
GO:000838023	Lung	MIAC	RNA splicing	44/967	434/18723	1.56e-05	1.07e-03	44
GO:001657022	Lung	MIAC	histone modification	45/967	463/18723	3.58e-05	1.97e-03	45

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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

USP49

SNV

Missense_Mutation

novel

c.2029N>C

p.Ser677Arg

p.S677R

Q70CQ1

protein_coding

tolerated_low_confidence(0.27)

benign(0)

TCGA-A2-A3Y0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

USP49

SNV

Missense_Mutation

c.175N>C

p.Glu59Gln

p.E59Q

Q70CQ1

protein_coding

tolerated(1)

benign(0.015)

TCGA-E2-A1IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

USP49

insertion

In_Frame_Ins

novel

c.1379_1380insTGTATTAAAAAACAAAACAAGGCTGGG

p.Tyr460_Lys461insValLeuLysAsnLysThrArgLeuGly

p.Y460_K461insVLKNKTRLG

Q70CQ1

protein_coding

TCGA-A8-A0A9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

USP49

insertion

Nonsense_Mutation

novel

c.1257_1258insTATAGTTAAAAAAAGGCAGGTGTGCCGGGCACGGT

p.Thr420TyrfsTer3

p.T420Yfs*3

Q70CQ1

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP49

insertion

In_Frame_Ins

novel

c.1399_1400insATGTTATCAGGG

p.Pro467delinsHisValIleArgAla

p.P467delinsHVIRA

Q70CQ1

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

USP49

insertion

Frame_Shift_Ins

novel

c.1397_1398insTATGGTTACAGAG

p.Glu466AspfsTer16

p.E466Dfs*16

Q70CQ1

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

USP49

insertion

Frame_Shift_Ins

novel

c.1843_1844insGAGGTCAGGAGGTCGAGACCATCCTGGCTAACATGGTGAAG

p.His615ArgfsTer36

p.H615Rfs*36

Q70CQ1

protein_coding

TCGA-BH-A0E2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

USP49

insertion

Nonsense_Mutation

novel

c.1701_1702insTCAGCTGTTCACTCTTCTTGAACTGCACAGCCCTTGG

p.Gly568SerfsTer7

p.G568Sfs*7

Q70CQ1

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

USP49

SNV

Missense_Mutation

novel

c.1049C>T

p.Pro350Leu

p.P350L

Q70CQ1

protein_coding

deleterious(0)

possibly_damaging(0.788)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

USP49

SNV

Missense_Mutation

novel

c.1549G>C

p.Asp517His

p.D517H

Q70CQ1

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

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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