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: CYP3A5

Gene summary for CYP3A5

Gene summary.

Gene information	Species	Human
	Gene symbol	CYP3A5
	Gene ID	1577
	Gene name	cytochrome P450 family 3 subfamily A member 5
	Gene Alias	CP35
	Cytomap	7q22.1
	Gene Type	protein-coding
	GO ID	GO:0001523
	UniProtAcc	P20815

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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
1577	CYP3A5	HTA11_3410_2000001011	Human	Colorectum	AD	2.81e-04	-7.75e-02	0.0155
1577	CYP3A5	HTA11_1938_2000001011	Human	Colorectum	AD	1.66e-08	6.36e-01	-0.0811
1577	CYP3A5	HTA11_78_2000001011	Human	Colorectum	AD	5.58e-09	6.83e-01	-0.1088
1577	CYP3A5	HTA11_347_2000001011	Human	Colorectum	AD	2.84e-02	3.12e-01	-0.1954
1577	CYP3A5	HTA11_99999974143_84620	Human	Colorectum	MSS	1.22e-03	-3.67e-01	0.3005
1577	CYP3A5	F007	Human	Colorectum	FAP	2.56e-05	5.68e-01	0.1176
1577	CYP3A5	A001-C-207	Human	Colorectum	FAP	1.07e-02	4.12e-01	0.1278
1577	CYP3A5	A015-C-203	Human	Colorectum	FAP	5.20e-27	6.43e-01	-0.1294
1577	CYP3A5	A015-C-204	Human	Colorectum	FAP	2.23e-08	5.36e-01	-0.0228
1577	CYP3A5	A002-C-201	Human	Colorectum	FAP	1.52e-09	4.19e-01	0.0324
1577	CYP3A5	A002-C-203	Human	Colorectum	FAP	3.76e-26	8.19e-01	0.2786
1577	CYP3A5	A001-C-119	Human	Colorectum	FAP	5.04e-06	4.29e-01	-0.1557
1577	CYP3A5	A001-C-108	Human	Colorectum	FAP	2.93e-24	6.99e-01	-0.0272
1577	CYP3A5	A002-C-021	Human	Colorectum	FAP	1.15e-07	4.11e-01	0.1171
1577	CYP3A5	A002-C-205	Human	Colorectum	FAP	7.54e-24	6.10e-01	-0.1236
1577	CYP3A5	A014-C-108	Human	Colorectum	FAP	2.60e-06	5.29e-01	-0.124
1577	CYP3A5	A001-C-104	Human	Colorectum	FAP	2.30e-18	6.64e-01	0.0184
1577	CYP3A5	A015-C-006	Human	Colorectum	FAP	3.38e-05	8.51e-02	-0.0994
1577	CYP3A5	A015-C-106	Human	Colorectum	FAP	5.21e-15	5.74e-01	-0.0511
1577	CYP3A5	A002-C-114	Human	Colorectum	FAP	8.86e-32	8.42e-01	-0.1561

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
Prostate		BPH: Benign Prostatic Hyperplasia

∗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:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0006066	Colorectum	AD	alcohol metabolic process	106/3918	353/18723	3.02e-05	5.57e-04	106
GO:0030258	Colorectum	AD	lipid modification	67/3918	212/18723	1.66e-04	2.27e-03	67
GO:0009410	Colorectum	AD	response to xenobiotic stimulus	128/3918	462/18723	2.69e-04	3.31e-03	128
GO:0034308	Colorectum	AD	primary alcohol metabolic process	35/3918	102/18723	1.16e-03	1.05e-02	35
GO:0008202	Colorectum	AD	steroid metabolic process	85/3918	319/18723	8.07e-03	4.75e-02	85
GO:00442702	Colorectum	MSS	cellular nitrogen compound catabolic process	141/3467	451/18723	2.95e-11	3.83e-09	141
GO:00060662	Colorectum	MSS	alcohol metabolic process	92/3467	353/18723	2.57e-04	3.46e-03	92
GO:00302582	Colorectum	MSS	lipid modification	57/3467	212/18723	1.64e-03	1.49e-02	57
GO:00094101	Colorectum	MSS	response to xenobiotic stimulus	110/3467	462/18723	2.36e-03	1.92e-02	110
GO:00442704	Colorectum	FAP	cellular nitrogen compound catabolic process	101/2622	451/18723	7.42e-07	3.44e-05	101
GO:00302583	Colorectum	FAP	lipid modification	52/2622	212/18723	2.84e-05	6.49e-04	52
GO:00094102	Colorectum	FAP	response to xenobiotic stimulus	87/2622	462/18723	2.15e-03	1.77e-02	87
GO:00060663	Colorectum	FAP	alcohol metabolic process	69/2622	353/18723	2.29e-03	1.85e-02	69
GO:00442705	Colorectum	CRC	cellular nitrogen compound catabolic process	78/2078	451/18723	4.48e-05	1.07e-03	78
GO:00302584	Colorectum	CRC	lipid modification	41/2078	212/18723	2.73e-04	4.38e-03	41
GO:00060664	Colorectum	CRC	alcohol metabolic process	57/2078	353/18723	2.37e-03	2.27e-02	57
GO:00094103	Colorectum	CRC	response to xenobiotic stimulus	69/2078	462/18723	6.34e-03	4.61e-02	69
GO:004427019	Esophagus	ESCC	cellular nitrogen compound catabolic process	288/8552	451/18723	3.03e-15	1.79e-13	288
GO:00060668	Esophagus	ESCC	alcohol metabolic process	202/8552	353/18723	7.32e-06	7.26e-05	202

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00980	Stomach	GC	Metabolism of xenobiotics by cytochrome P450	15/708	78/8465	1.77e-03	1.16e-02	8.15e-03	15
hsa009801	Stomach	GC	Metabolism of xenobiotics by cytochrome P450	15/708	78/8465	1.77e-03	1.16e-02	8.15e-03	15

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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

CYP3A5

SNV

Missense_Mutation

novel

c.1031C>T

p.Pro344Leu

p.P344L

P20815

protein_coding

tolerated(0.14)

benign(0.05)

TCGA-A2-A4RW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CYP3A5

SNV

Missense_Mutation

novel

c.1502N>C

p.Gly501Ala

p.G501A

P20815

protein_coding

tolerated(0.16)

possibly_damaging(0.506)

TCGA-A7-A6VY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

CYP3A5

SNV

Missense_Mutation

c.1395N>C

p.Lys465Asn

p.K465N

P20815

protein_coding

deleterious(0.03)

benign(0.027)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CYP3A5

insertion

In_Frame_Ins

novel

c.386_387insCCACAAGAC

p.Ile129_Arg130insHisLysThr

p.I129_R130insHKT

P20815

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CYP3A5

insertion

Frame_Shift_Ins

novel

c.384_385insCTCTCTCAACA

p.Ile129LeufsTer33

p.I129Lfs*33

P20815

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CYP3A5

SNV

Missense_Mutation

novel

c.838A>C

p.Asn280His

p.N280H

P20815

protein_coding

deleterious(0.02)

benign(0.2)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CYP3A5

SNV

Missense_Mutation

novel

c.210A>C

p.Lys70Asn

p.K70N

P20815

protein_coding

tolerated(0.09)

benign(0.11)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CYP3A5

SNV

Missense_Mutation

c.652N>G

p.Pro218Ala

p.P218A

P20815

protein_coding

deleterious(0)

possibly_damaging(0.752)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CYP3A5

SNV

Missense_Mutation

novel

c.877N>G

p.Leu293Val

p.L293V

P20815

protein_coding

tolerated(0.29)

benign(0)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CYP3A5

SNV

Missense_Mutation

c.742T>G

p.Phe248Val

p.F248V

P20815

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=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
1577	CYP3A5	ENZYME, CYTOCHROME P450, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		fluticasone propionate		18695978
1577	CYP3A5	ENZYME, CYTOCHROME P450, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		haloperidol	HALOPERIDOL	27023437,18695978
1577	CYP3A5	ENZYME, CYTOCHROME P450, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		TESMILIFENE	TESMILIFENE
1577	CYP3A5	ENZYME, CYTOCHROME P450, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		diazepam	DIAZEPAM	18695978
1577	CYP3A5	ENZYME, CYTOCHROME P450, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		rosuvastatin	ROSUVASTATIN	20207952
1577	CYP3A5	ENZYME, CYTOCHROME P450, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		cilostazol	CILOSTAZOL
1577	CYP3A5	ENZYME, CYTOCHROME P450, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		buprenorphine	BUPRENORPHINE	18695978
1577	CYP3A5	ENZYME, CYTOCHROME P450, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		tramadol	TRAMADOL	18695978
1577	CYP3A5	ENZYME, CYTOCHROME P450, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		apixaban	APIXABAN	28678049,29457840
1577	CYP3A5	ENZYME, CYTOCHROME P450, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		meperidine	MEPERIDINE	18695978

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