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: COPB2

Gene summary for COPB2

Gene summary.

Gene information	Species	Human
	Gene symbol	COPB2
	Gene ID	9276
	Gene name	COPI coat complex subunit beta 2
	Gene Alias	MCPH19
	Cytomap	3q23
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	P35606

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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
9276	COPB2	GSM4909281	Human	Breast	IDC	5.69e-06	3.50e-01	0.21
9276	COPB2	GSM4909285	Human	Breast	IDC	2.80e-10	4.07e-01	0.21
9276	COPB2	GSM4909293	Human	Breast	IDC	2.20e-12	4.03e-01	0.1581
9276	COPB2	GSM4909296	Human	Breast	IDC	6.81e-05	-1.55e-01	0.1524
9276	COPB2	GSM4909297	Human	Breast	IDC	6.52e-04	-1.14e-01	0.1517
9276	COPB2	GSM4909304	Human	Breast	IDC	5.49e-03	2.65e-01	0.1636
9276	COPB2	GSM4909311	Human	Breast	IDC	2.15e-14	-1.26e-01	0.1534
9276	COPB2	GSM4909312	Human	Breast	IDC	1.44e-05	4.00e-02	0.1552
9276	COPB2	GSM4909319	Human	Breast	IDC	1.38e-14	-1.64e-01	0.1563
9276	COPB2	GSM4909321	Human	Breast	IDC	1.75e-06	-1.36e-01	0.1559
9276	COPB2	brca2	Human	Breast	Precancer	1.37e-09	3.29e-01	-0.024
9276	COPB2	brca3	Human	Breast	Precancer	2.79e-03	2.58e-01	-0.0263
9276	COPB2	NCCBC14	Human	Breast	DCIS	2.54e-14	5.67e-01	0.2021
9276	COPB2	P1	Human	Breast	IDC	1.11e-03	-1.50e-02	0.1527
9276	COPB2	P2	Human	Breast	IDC	6.53e-07	4.89e-01	0.21
9276	COPB2	DCIS2	Human	Breast	DCIS	4.64e-60	3.00e-01	0.0085
9276	COPB2	HTA11_347_2000001011	Human	Colorectum	AD	7.55e-06	4.27e-01	-0.1954
9276	COPB2	HTA11_99999970781_79442	Human	Colorectum	MSS	2.46e-05	4.72e-01	0.294
9276	COPB2	A015-C-203	Human	Colorectum	FAP	2.64e-08	-1.64e-01	-0.1294
9276	COPB2	A001-C-108	Human	Colorectum	FAP	1.73e-02	1.15e-02	-0.0272

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:00068914	Esophagus	ESCC	intra-Golgi vesicle-mediated transport	26/8552	33/18723	1.06e-04	7.43e-04	26
GO:19019987	Esophagus	ESCC	toxin transport	28/8552	40/18723	1.61e-03	7.50e-03	28
GO:004819311	Liver	Cirrhotic	Golgi vesicle transport	153/4634	296/18723	1.02e-23	6.43e-21	153
GO:000688811	Liver	Cirrhotic	endoplasmic reticulum to Golgi vesicle-mediated transport	77/4634	130/18723	5.78e-17	7.56e-15	77
GO:00068905	Liver	Cirrhotic	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	29/4634	52/18723	1.69e-06	3.22e-05	29
GO:004819321	Liver	HCC	Golgi vesicle transport	217/7958	296/18723	2.58e-27	1.02e-24	217
GO:000688821	Liver	HCC	endoplasmic reticulum to Golgi vesicle-mediated transport	100/7958	130/18723	1.15e-15	8.67e-14	100
GO:000689011	Liver	HCC	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	36/7958	52/18723	8.79e-05	7.66e-04	36
GO:0006891	Liver	HCC	intra-Golgi vesicle-mediated transport	22/7958	33/18723	4.38e-03	1.90e-02	22
GO:004819315	Oral cavity	OSCC	Golgi vesicle transport	209/7305	296/18723	1.39e-28	6.30e-26	209
GO:00068888	Oral cavity	OSCC	endoplasmic reticulum to Golgi vesicle-mediated transport	97/7305	130/18723	1.42e-16	1.15e-14	97
GO:000689010	Oral cavity	OSCC	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	40/7305	52/18723	2.86e-08	5.50e-07	40
GO:00068913	Oral cavity	OSCC	intra-Golgi vesicle-mediated transport	23/7305	33/18723	3.47e-04	2.12e-03	23
GO:19019986	Oral cavity	OSCC	toxin transport	25/7305	40/18723	2.22e-03	1.00e-02	25
GO:004819316	Oral cavity	LP	Golgi vesicle transport	141/4623	296/18723	6.11e-18	1.06e-15	141
GO:000688814	Oral cavity	LP	endoplasmic reticulum to Golgi vesicle-mediated transport	67/4623	130/18723	3.74e-11	2.39e-09	67
GO:000689015	Oral cavity	LP	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	29/4623	52/18723	1.60e-06	3.79e-05	29
GO:190199812	Oral cavity	LP	toxin transport	19/4623	40/18723	1.44e-03	1.14e-02	19
GO:000689111	Oral cavity	LP	intra-Golgi vesicle-mediated transport	16/4623	33/18723	2.59e-03	1.83e-02	16
GO:004819322	Oral cavity	EOLP	Golgi vesicle transport	72/2218	296/18723	1.43e-09	9.55e-08	72

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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

COPB2

SNV

Missense_Mutation

novel

c.1682T>G

p.Met561Arg

p.M561R

P35606

protein_coding

deleterious(0)

possibly_damaging(0.61)

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

COPB2

SNV

Missense_Mutation

novel

c.2240N>T

p.Arg747Ile

p.R747I

P35606

protein_coding

deleterious(0.02)

benign(0.062)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

COPB2

SNV

Missense_Mutation

novel

c.1894N>A

p.Gln632Lys

p.Q632K

P35606

protein_coding

tolerated(0.17)

benign(0.01)

TCGA-BH-A0AV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

COPB2

SNV

Missense_Mutation

c.935G>A

p.Gly312Glu

p.G312E

P35606

protein_coding

deleterious(0)

probably_damaging(0.95)

TCGA-D8-A142-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamid

COPB2

SNV

Missense_Mutation

novel

c.547N>A

p.Gly183Arg

p.G183R

P35606

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-LL-A8F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

COPB2

insertion

Frame_Shift_Ins

novel

c.1679_1680insTTCTCCTTTCTCAGTGCCCCCTTTAAATGTTG

p.Met561SerfsTer15

p.M561Sfs*15

P35606

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

COPB2

deletion

Frame_Shift_Del

novel

c.2349delN

p.Ala784GlnfsTer18

p.A784Qfs*18

P35606

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

COPB2

insertion

In_Frame_Ins

rs766565677

c.592_593insGGA

p.Asp198delinsGlyAsn

p.D198delinsGN

P35606

protein_coding

TCGA-E9-A1NG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

COPB2

SNV

Missense_Mutation

c.2582N>T

p.Thr861Ile

p.T861I

P35606

protein_coding

tolerated(0.29)

benign(0.034)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

COPB2

SNV

Missense_Mutation

rs745412053

c.902N>A

p.Arg301Gln

p.R301Q

P35606

protein_coding

deleterious(0.02)

benign(0.241)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

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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