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: COPA

Gene summary for COPA

Gene summary.

Gene information	Species	Human
	Gene symbol	COPA
	Gene ID	1314
	Gene name	COPI coat complex subunit alpha
	Gene Alias	AILJK
	Cytomap	1q23.2
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	P53621

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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
1314	COPA	HTA11_1938_2000001011	Human	Colorectum	AD	3.14e-09	6.96e-01	-0.0811
1314	COPA	HTA11_78_2000001011	Human	Colorectum	AD	1.45e-08	6.14e-01	-0.1088
1314	COPA	HTA11_347_2000001011	Human	Colorectum	AD	7.30e-25	8.82e-01	-0.1954
1314	COPA	HTA11_411_2000001011	Human	Colorectum	SER	3.51e-04	7.43e-01	-0.2602
1314	COPA	HTA11_696_2000001011	Human	Colorectum	AD	3.05e-03	5.12e-01	-0.1464
1314	COPA	HTA11_1391_2000001011	Human	Colorectum	AD	3.03e-09	7.04e-01	-0.059
1314	COPA	HTA11_866_3004761011	Human	Colorectum	AD	1.49e-07	4.47e-01	0.096
1314	COPA	HTA11_7663_2000001011	Human	Colorectum	SER	3.34e-02	4.62e-01	0.0131
1314	COPA	HTA11_7469_2000001011	Human	Colorectum	AD	4.28e-02	5.58e-01	-0.0124
1314	COPA	HTA11_6818_2000001021	Human	Colorectum	AD	1.59e-03	4.03e-01	0.0588
1314	COPA	HTA11_99999970781_79442	Human	Colorectum	MSS	2.34e-07	6.27e-01	0.294
1314	COPA	HTA11_99999965104_69814	Human	Colorectum	MSS	4.42e-18	9.28e-01	0.281
1314	COPA	HTA11_99999971662_82457	Human	Colorectum	MSS	3.60e-10	8.72e-01	0.3859
1314	COPA	A002-C-010	Human	Colorectum	FAP	1.23e-02	-1.59e-01	0.242
1314	COPA	A015-C-203	Human	Colorectum	FAP	1.28e-20	-3.65e-01	-0.1294
1314	COPA	A014-C-040	Human	Colorectum	FAP	1.41e-03	-5.21e-01	-0.1184
1314	COPA	A002-C-201	Human	Colorectum	FAP	8.57e-09	-2.34e-01	0.0324
1314	COPA	A002-C-203	Human	Colorectum	FAP	6.40e-04	-8.64e-02	0.2786
1314	COPA	A001-C-108	Human	Colorectum	FAP	2.61e-15	-3.02e-01	-0.0272
1314	COPA	A002-C-205	Human	Colorectum	FAP	3.46e-17	-4.86e-01	-0.1236

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:0048193	Colorectum	AD	Golgi vesicle transport	109/3918	296/18723	1.80e-10	1.68e-08	109
GO:0006890	Colorectum	AD	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	27/3918	52/18723	7.67e-07	2.70e-05	27
GO:0050878	Colorectum	AD	regulation of body fluid levels	108/3918	379/18723	2.54e-04	3.20e-03	108
GO:0006888	Colorectum	AD	endoplasmic reticulum to Golgi vesicle-mediated transport	44/3918	130/18723	4.13e-04	4.68e-03	44
GO:0007589	Colorectum	AD	body fluid secretion	33/3918	93/18723	8.26e-04	8.13e-03	33
GO:00481931	Colorectum	SER	Golgi vesicle transport	79/2897	296/18723	4.20e-07	2.15e-05	79
GO:00068901	Colorectum	SER	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	20/2897	52/18723	4.80e-05	1.18e-03	20
GO:0022600	Colorectum	SER	digestive system process	29/2897	104/18723	8.57e-04	1.05e-02	29
GO:00068881	Colorectum	SER	endoplasmic reticulum to Golgi vesicle-mediated transport	34/2897	130/18723	1.13e-03	1.29e-02	34
GO:00508781	Colorectum	SER	regulation of body fluid levels	81/2897	379/18723	1.28e-03	1.43e-02	81
GO:00075891	Colorectum	SER	body fluid secretion	26/2897	93/18723	1.49e-03	1.60e-02	26
GO:0032941	Colorectum	SER	secretion by tissue	13/2897	38/18723	3.40e-03	2.90e-02	13
GO:00481932	Colorectum	MSS	Golgi vesicle transport	101/3467	296/18723	9.09e-11	9.77e-09	101
GO:00068902	Colorectum	MSS	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	26/3467	52/18723	2.66e-07	1.10e-05	26
GO:00068882	Colorectum	MSS	endoplasmic reticulum to Golgi vesicle-mediated transport	44/3467	130/18723	2.17e-05	4.60e-04	44
GO:00508782	Colorectum	MSS	regulation of body fluid levels	99/3467	379/18723	1.40e-04	2.07e-03	99
GO:00075892	Colorectum	MSS	body fluid secretion	29/3467	93/18723	2.21e-03	1.84e-02	29
GO:00226001	Colorectum	MSS	digestive system process	31/3467	104/18723	3.46e-03	2.59e-02	31
GO:00481934	Colorectum	FAP	Golgi vesicle transport	77/2622	296/18723	2.86e-08	2.62e-06	77
GO:00068904	Colorectum	FAP	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	18/2622	52/18723	1.48e-04	2.29e-03	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

COPA

SNV

Missense_Mutation

novel

c.2605N>A

p.Glu869Lys

p.E869K

P53621

protein_coding

tolerated(0.41)

benign(0.001)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

COPA

SNV

Missense_Mutation

c.2635N>T

p.Leu879Phe

p.L879F

P53621

protein_coding

tolerated(0.06)

benign(0.055)

TCGA-A7-A26I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

COPA

SNV

Missense_Mutation

novel

c.1597A>G

p.Ile533Val

p.I533V

P53621

protein_coding

tolerated(0.44)

benign(0.003)

TCGA-AC-A3W5-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

COPA

SNV

Missense_Mutation

novel

c.2098N>A

p.Glu700Lys

p.E700K

P53621

protein_coding

deleterious(0)

probably_damaging(0.958)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

COPA

SNV

Missense_Mutation

rs774710055

c.3697C>T

p.Arg1233Cys

p.R1233C

P53621

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.986)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

COPA

SNV

Missense_Mutation

novel

c.3115C>T

p.Arg1039Cys

p.R1039C

P53621

protein_coding

deleterious(0)

probably_damaging(0.946)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

COPA

SNV

Missense_Mutation

c.198C>G

p.Phe66Leu

p.F66L

P53621

protein_coding

tolerated(0.18)

probably_damaging(0.999)

TCGA-C8-A12K-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

COPA

SNV

Missense_Mutation

c.1109N>T

p.Tyr370Phe

p.Y370F

P53621

protein_coding

tolerated(0.19)

benign(0.034)

TCGA-C8-A12L-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

COPA

SNV

Missense_Mutation

c.3244N>G

p.Leu1082Val

p.L1082V

P53621

protein_coding

tolerated(0.22)

benign(0.094)

TCGA-E2-A15O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

COPA

SNV

Missense_Mutation

c.214N>C

p.Asp72His

p.D72H

P53621

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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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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