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: COPS5

Gene summary for COPS5

Gene summary.

Gene information	Species	Human
	Gene symbol	COPS5
	Gene ID	10987
	Gene name	COP9 signalosome subunit 5
	Gene Alias	CSN5
	Cytomap	8q13.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	A0A024R7W9

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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
10987	COPS5	HTA11_2487_2000001011	Human	Colorectum	SER	4.07e-02	1.83e-01	-0.1808
10987	COPS5	HTA11_78_2000001011	Human	Colorectum	AD	1.53e-03	3.29e-01	-0.1088
10987	COPS5	HTA11_347_2000001011	Human	Colorectum	AD	2.96e-07	2.54e-01	-0.1954
10987	COPS5	HTA11_866_3004761011	Human	Colorectum	AD	6.99e-03	1.79e-01	0.096
10987	COPS5	HTA11_6801_2000001011	Human	Colorectum	SER	9.65e-03	3.66e-01	0.0171
10987	COPS5	HTA11_99999970781_79442	Human	Colorectum	MSS	2.04e-06	2.61e-01	0.294
10987	COPS5	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.17e-02	5.83e-01	0.3487
10987	COPS5	HTA11_99999971662_82457	Human	Colorectum	MSS	1.20e-13	4.72e-01	0.3859
10987	COPS5	HTA11_99999974143_84620	Human	Colorectum	MSS	4.73e-02	1.49e-01	0.3005
10987	COPS5	LZE4T	Human	Esophagus	ESCC	3.43e-24	8.28e-01	0.0811
10987	COPS5	LZE5T	Human	Esophagus	ESCC	6.45e-03	3.05e-01	0.0514
10987	COPS5	LZE7T	Human	Esophagus	ESCC	5.70e-09	4.03e-01	0.0667
10987	COPS5	LZE8T	Human	Esophagus	ESCC	2.35e-17	6.14e-01	0.067
10987	COPS5	LZE20T	Human	Esophagus	ESCC	1.05e-15	7.09e-01	0.0662
10987	COPS5	LZE22D1	Human	Esophagus	HGIN	3.03e-04	1.83e-01	0.0595
10987	COPS5	LZE22T	Human	Esophagus	ESCC	3.21e-02	3.54e-01	0.068
10987	COPS5	LZE24T	Human	Esophagus	ESCC	1.41e-35	1.16e+00	0.0596
10987	COPS5	LZE21T	Human	Esophagus	ESCC	6.89e-03	2.47e-01	0.0655
10987	COPS5	LZE6T	Human	Esophagus	ESCC	4.84e-10	4.78e-01	0.0845
10987	COPS5	P1T-E	Human	Esophagus	ESCC	1.34e-15	8.50e-01	0.0875

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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:190589725	Esophagus	HGIN	regulation of response to endoplasmic reticulum stress	31/2587	82/18723	5.25e-08	2.91e-06	31
GO:003096817	Esophagus	HGIN	endoplasmic reticulum unfolded protein response	24/2587	74/18723	3.39e-05	8.61e-04	24
GO:00003383	Esophagus	HGIN	protein deneddylation	6/2587	10/18723	8.81e-04	1.13e-02	6
GO:00706463	Esophagus	HGIN	protein modification by small protein removal	34/2587	157/18723	4.68e-03	4.02e-02	34
GO:0034976111	Esophagus	ESCC	response to endoplasmic reticulum stress	192/8552	256/18723	7.15e-22	1.30e-19	192
GO:0006413110	Esophagus	ESCC	translational initiation	100/8552	118/18723	1.16e-18	1.25e-16	100
GO:0035966111	Esophagus	ESCC	response to topologically incorrect protein	125/8552	159/18723	1.44e-17	1.27e-15	125
GO:0006986111	Esophagus	ESCC	response to unfolded protein	107/8552	137/18723	7.01e-15	3.87e-13	107
GO:0035967111	Esophagus	ESCC	cellular response to topologically incorrect protein	90/8552	116/18723	1.94e-12	8.11e-11	90
GO:0034620111	Esophagus	ESCC	cellular response to unfolded protein	74/8552	96/18723	3.10e-10	8.66e-09	74
GO:003096818	Esophagus	ESCC	endoplasmic reticulum unfolded protein response	59/8552	74/18723	1.90e-09	4.36e-08	59
GO:1905897111	Esophagus	ESCC	regulation of response to endoplasmic reticulum stress	63/8552	82/18723	8.16e-09	1.66e-07	63
GO:003109818	Esophagus	ESCC	stress-activated protein kinase signaling cascade	154/8552	247/18723	8.53e-08	1.44e-06	154
GO:00510908	Esophagus	ESCC	regulation of DNA-binding transcription factor activity	252/8552	440/18723	5.22e-07	6.97e-06	252
GO:005140318	Esophagus	ESCC	stress-activated MAPK cascade	147/8552	239/18723	5.43e-07	7.18e-06	147
GO:00510918	Esophagus	ESCC	positive regulation of DNA-binding transcription factor activity	155/8552	260/18723	3.83e-06	4.14e-05	155
GO:007030217	Esophagus	ESCC	regulation of stress-activated protein kinase signaling cascade	119/8552	195/18723	1.07e-05	1.01e-04	119
GO:003287217	Esophagus	ESCC	regulation of stress-activated MAPK cascade	116/8552	192/18723	2.63e-05	2.21e-04	116
GO:00072549	Esophagus	ESCC	JNK cascade	102/8552	167/18723	4.22e-05	3.39e-04	102
GO:199018210	Esophagus	ESCC	exosomal secretion	18/8552	20/18723	4.55e-05	3.58e-04	18

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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

COPS5

insertion

Frame_Shift_Ins

novel

c.98_99insC

p.Lys33AsnfsTer15

p.K33Nfs*15

Q92905

protein_coding

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

COPS5

insertion

In_Frame_Ins

novel

c.96_97insCTTGAGCCCAGTGTCGACATGCACCTTGTTTGGGTCTTC

p.Asp32_Lys33insLeuGluProSerValAspMetHisLeuValTrpValPhe

p.D32_K33insLEPSVDMHLVWVF

Q92905

protein_coding

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

COPS5

SNV

Missense_Mutation

c.592N>A

p.Glu198Lys

p.E198K

Q92905

protein_coding

tolerated(0.26)

benign(0.367)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

COPS5

SNV

Missense_Mutation

novel

c.94N>A

p.Asp32Asn

p.D32N

Q92905

protein_coding

tolerated(0.11)

benign(0.056)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

COPS5

SNV

Missense_Mutation

novel

c.715N>C

p.Glu239Gln

p.E239Q

Q92905

protein_coding

tolerated(0.05)

benign(0.027)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

COPS5

SNV

Missense_Mutation

novel

c.86N>G

p.Tyr29Cys

p.Y29C

Q92905

protein_coding

deleterious(0)

possibly_damaging(0.873)

TCGA-AD-6964-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folfox

COPS5

SNV

Missense_Mutation

rs143525514

c.872C>T

p.Thr291Met

p.T291M

Q92905

protein_coding

tolerated(0.13)

benign(0.15)

TCGA-AG-3902-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

COPS5

SNV

Missense_Mutation

c.881N>A

p.Arg294Gln

p.R294Q

Q92905

protein_coding

tolerated(0.16)

benign(0.048)

TCGA-EI-6882-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

COPS5

SNV

Missense_Mutation

c.804T>A

p.Asp268Glu

p.D268E

Q92905

protein_coding

deleterious(0.02)

probably_damaging(0.976)

TCGA-A5-A0GA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

taxol

COPS5

SNV

Missense_Mutation

c.34N>G

p.Thr12Ala

p.T12A

Q92905

protein_coding

tolerated(0.19)

benign(0.006)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid 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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