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: CAT

Gene summary for CAT

Gene summary.

Gene information	Species	Human
	Gene symbol	CAT
	Gene ID	847
	Gene name	catalase
	Gene Alias	CAT
	Cytomap	11p13
	Gene Type	protein-coding
	GO ID	GO:0000302
	UniProtAcc	P04040

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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
847	CAT	HTA11_78_2000001011	Human	Colorectum	AD	2.00e-03	5.07e-01	-0.1088
847	CAT	HTA11_347_2000001011	Human	Colorectum	AD	3.90e-09	5.05e-01	-0.1954
847	CAT	HTA11_1391_2000001011	Human	Colorectum	AD	5.60e-05	6.23e-01	-0.059
847	CAT	HTA11_6801_2000001011	Human	Colorectum	SER	1.24e-03	8.69e-01	0.0171
847	CAT	HTA11_7696_3000711011	Human	Colorectum	AD	1.99e-07	3.86e-01	0.0674
847	CAT	HTA11_99999970781_79442	Human	Colorectum	MSS	2.54e-08	4.98e-01	0.294
847	CAT	HTA11_99999971662_82457	Human	Colorectum	MSS	1.80e-09	5.47e-01	0.3859
847	CAT	A015-C-203	Human	Colorectum	FAP	7.08e-08	-2.11e-01	-0.1294
847	CAT	A014-C-040	Human	Colorectum	FAP	1.14e-02	-3.22e-01	-0.1184
847	CAT	A002-C-201	Human	Colorectum	FAP	2.55e-07	-2.21e-01	0.0324
847	CAT	A001-C-119	Human	Colorectum	FAP	1.69e-02	-2.32e-01	-0.1557
847	CAT	A001-C-108	Human	Colorectum	FAP	4.25e-02	-1.98e-01	-0.0272
847	CAT	A002-C-205	Human	Colorectum	FAP	5.71e-08	-2.29e-01	-0.1236
847	CAT	A015-C-006	Human	Colorectum	FAP	2.24e-06	-2.79e-01	-0.0994
847	CAT	A015-C-106	Human	Colorectum	FAP	3.05e-03	-1.14e-01	-0.0511
847	CAT	A002-C-114	Human	Colorectum	FAP	2.00e-07	-2.52e-01	-0.1561
847	CAT	A015-C-104	Human	Colorectum	FAP	2.19e-06	-8.53e-02	-0.1899
847	CAT	A001-C-014	Human	Colorectum	FAP	1.39e-03	-2.30e-01	0.0135
847	CAT	A002-C-016	Human	Colorectum	FAP	2.38e-06	-2.14e-01	0.0521
847	CAT	A015-C-002	Human	Colorectum	FAP	1.48e-03	-2.53e-01	-0.0763

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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
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:007252218	Skin	cSCC	purine-containing compound biosynthetic process	78/4864	200/18723	3.44e-05	3.74e-04	78
GO:0042594110	Skin	cSCC	response to starvation	77/4864	197/18723	3.52e-05	3.82e-04	77
GO:190129310	Skin	cSCC	nucleoside phosphate biosynthetic process	95/4864	256/18723	5.21e-05	5.31e-04	95
GO:000916510	Skin	cSCC	nucleotide biosynthetic process	94/4864	254/18723	6.40e-05	6.25e-04	94
GO:0009152111	Skin	cSCC	purine ribonucleotide biosynthetic process	67/4864	169/18723	6.60e-05	6.43e-04	67
GO:00065758	Skin	cSCC	cellular modified amino acid metabolic process	73/4864	188/18723	7.11e-05	6.85e-04	73
GO:003166728	Skin	cSCC	response to nutrient levels	160/4864	474/18723	8.44e-05	8.02e-04	160
GO:000616418	Skin	cSCC	purine nucleotide biosynthetic process	73/4864	191/18723	1.28e-04	1.17e-03	73
GO:004668624	Skin	cSCC	response to cadmium ion	32/4864	68/18723	1.44e-04	1.29e-03	32
GO:000150323	Skin	cSCC	ossification	137/4864	408/18723	3.39e-04	2.68e-03	137
GO:0032868110	Skin	cSCC	response to insulin	93/4864	264/18723	5.10e-04	3.83e-03	93
GO:0009410110	Skin	cSCC	response to xenobiotic stimulus	151/4864	462/18723	6.76e-04	4.82e-03	151
GO:000974328	Skin	cSCC	response to carbohydrate	88/4864	253/18723	1.11e-03	7.31e-03	88
GO:00164858	Skin	cSCC	protein processing	79/4864	225/18723	1.43e-03	9.02e-03	79
GO:003428427	Skin	cSCC	response to monosaccharide	79/4864	225/18723	1.43e-03	9.02e-03	79
GO:000941621	Skin	cSCC	response to light stimulus	107/4864	320/18723	1.66e-03	1.02e-02	107
GO:000758416	Skin	cSCC	response to nutrient	63/4864	174/18723	1.78e-03	1.08e-02	63
GO:00066954	Skin	cSCC	cholesterol biosynthetic process	25/4864	57/18723	2.55e-03	1.45e-02	25
GO:19026534	Skin	cSCC	secondary alcohol biosynthetic process	25/4864	57/18723	2.55e-03	1.45e-02	25
GO:005109214	Skin	cSCC	positive regulation of NF-kappaB transcription factor activity	55/4864	152/18723	3.40e-03	1.84e-02	55

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05208	Colorectum	AD	Chemical carcinogenesis - reactive oxygen species	126/2092	223/8465	1.01e-24	1.68e-22	1.07e-22	126
hsa05014	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa05022	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa01200	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa04213	Colorectum	AD	Longevity regulating pathway - multiple species	27/2092	62/8465	8.72e-04	5.96e-03	3.80e-03	27
hsa04211	Colorectum	AD	Longevity regulating pathway	33/2092	89/8465	6.15e-03	2.68e-02	1.71e-02	33
hsa00630	Colorectum	AD	Glyoxylate and dicarboxylate metabolism	14/2092	30/8465	7.25e-03	2.97e-02	1.89e-02	14
hsa052081	Colorectum	AD	Chemical carcinogenesis - reactive oxygen species	126/2092	223/8465	1.01e-24	1.68e-22	1.07e-22	126
hsa050141	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa050221	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa012001	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa042131	Colorectum	AD	Longevity regulating pathway - multiple species	27/2092	62/8465	8.72e-04	5.96e-03	3.80e-03	27
hsa042111	Colorectum	AD	Longevity regulating pathway	33/2092	89/8465	6.15e-03	2.68e-02	1.71e-02	33
hsa006301	Colorectum	AD	Glyoxylate and dicarboxylate metabolism	14/2092	30/8465	7.25e-03	2.97e-02	1.89e-02	14
hsa050222	Colorectum	SER	Pathways of neurodegeneration - multiple diseases	168/1580	476/8465	6.23e-19	2.07e-17	1.50e-17	168
hsa050142	Colorectum	SER	Amyotrophic lateral sclerosis	138/1580	364/8465	9.89e-19	2.99e-17	2.17e-17	138
hsa050223	Colorectum	SER	Pathways of neurodegeneration - multiple diseases	168/1580	476/8465	6.23e-19	2.07e-17	1.50e-17	168
hsa050143	Colorectum	SER	Amyotrophic lateral sclerosis	138/1580	364/8465	9.89e-19	2.99e-17	2.17e-17	138
hsa052084	Colorectum	MSS	Chemical carcinogenesis - reactive oxygen species	118/1875	223/8465	2.71e-24	4.54e-22	2.78e-22	118
hsa050224	Colorectum	MSS	Pathways of neurodegeneration - multiple diseases	192/1875	476/8465	2.79e-20	1.04e-18	6.36e-19	192

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
CAT	AT2L	Lung	AAH	SFTPC,PEBP4,SFTPA1, etc.	2.44e-01
CAT	STM	Lung	AAH	SFTPC,PEBP4,SFTPA1, etc.	5.86e-02
CAT	AT2	Lung	AAH	SFTPC,PEBP4,SFTPA1, etc.	5.13e-01
CAT	AT2	Lung	ADJ	SFTPC,PEBP4,SFTPA1, etc.	4.58e-01
CAT	AT2	Lung	AIS	SFTPC,PEBP4,SFTPA1, etc.	3.84e-01
CAT	STM	Lung	AIS	SFTPC,PEBP4,SFTPA1, etc.	8.39e-02
CAT	AT2	Lung	MIAC	SFTPC,PEBP4,SFTPA1, etc.	3.21e-01

∗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

CAT

SNV

Missense_Mutation

rs573379158

c.1559N>T

p.Ala520Val

p.A520V

P04040

protein_coding

tolerated_low_confidence(0.11)

benign(0)

TCGA-E2-A153-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CAT

insertion

Nonsense_Mutation

novel

c.883_884insTGTATTCTATTATTTGAATTTTTACACTC

p.Asn295MetfsTer6

p.N295Mfs*6

P04040

protein_coding

TCGA-A8-A07L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

CAT

SNV

Missense_Mutation

rs756388518

c.385N>T

p.Pro129Ser

p.P129S

P04040

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CAT

SNV

Missense_Mutation

rs573379158

c.1559C>T

p.Ala520Val

p.A520V

P04040

protein_coding

tolerated_low_confidence(0.11)

benign(0)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CAT

SNV

Missense_Mutation

c.988N>A

p.Glu330Lys

p.E330K

P04040

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-FU-A23K-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

CAT

SNV

Missense_Mutation

c.415N>A

p.Glu139Lys

p.E139K

P04040

protein_coding

deleterious(0.01)

possibly_damaging(0.552)

TCGA-VS-A9UP-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CAT

SNV

Missense_Mutation

rs752948472

c.380N>A

p.Arg127Gln

p.R127Q

P04040

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

CAT

SNV

Missense_Mutation

rs777189700

c.1145N>A

p.Arg382Gln

p.R382Q

P04040

protein_coding

tolerated(0.26)

benign(0.015)

TCGA-AZ-4313-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

CAT

SNV

Missense_Mutation

rs778007071

c.749N>T

p.Ala250Val

p.A250V

P04040

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AZ-6598-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CAT

SNV

Missense_Mutation

novel

c.468N>T

p.Arg156Ser

p.R156S

P04040

protein_coding

deleterious(0.02)

possibly_damaging(0.631)

TCGA-AG-3892-01

Colorectum

rectum adenocarcinoma

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
847	CAT	ENZYME, DRUGGABLE GENOME		EUK-189
847	CAT	ENZYME, DRUGGABLE GENOME		ethanol	ALCOHOL	25514903
847	CAT	ENZYME, DRUGGABLE GENOME		anthracyclines and related substances		19863340

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