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: SETD5

Gene summary for SETD5

Gene summary.

Gene information	Species	Human
	Gene symbol	SETD5
	Gene ID	55209
	Gene name	SET domain containing 5
	Gene Alias	SETD5
	Cytomap	3p25.3
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	Q9C0A6

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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
55209	SETD5	CCI_1	Human	Cervix	CC	8.54e-04	6.40e-01	0.528
55209	SETD5	CCI_2	Human	Cervix	CC	2.17e-09	9.68e-01	0.5249
55209	SETD5	CCI_3	Human	Cervix	CC	3.27e-12	9.17e-01	0.516
55209	SETD5	HTA11_1938_2000001011	Human	Colorectum	AD	5.08e-05	5.03e-01	-0.0811
55209	SETD5	HTA11_347_2000001011	Human	Colorectum	AD	6.56e-09	5.77e-01	-0.1954
55209	SETD5	HTA11_1391_2000001011	Human	Colorectum	AD	7.40e-07	6.34e-01	-0.059
55209	SETD5	HTA11_5212_2000001011	Human	Colorectum	AD	2.71e-02	-3.97e-01	-0.2061
55209	SETD5	HTA11_7663_2000001011	Human	Colorectum	SER	1.01e-03	6.33e-01	0.0131
55209	SETD5	HTA11_6818_2000001021	Human	Colorectum	AD	2.59e-08	6.23e-01	0.0588
55209	SETD5	HTA11_99999970781_79442	Human	Colorectum	MSS	1.45e-09	6.49e-01	0.294
55209	SETD5	HTA11_99999965062_69753	Human	Colorectum	MSI-H	8.62e-16	1.23e+00	0.3487
55209	SETD5	HTA11_99999965104_69814	Human	Colorectum	MSS	7.75e-14	7.88e-01	0.281
55209	SETD5	HTA11_99999971662_82457	Human	Colorectum	MSS	1.88e-09	9.20e-01	0.3859
55209	SETD5	F007	Human	Colorectum	FAP	1.19e-02	-2.00e-01	0.1176
55209	SETD5	A001-C-207	Human	Colorectum	FAP	5.94e-03	-1.66e-01	0.1278
55209	SETD5	A015-C-203	Human	Colorectum	FAP	2.92e-36	-4.04e-01	-0.1294
55209	SETD5	A015-C-204	Human	Colorectum	FAP	2.17e-05	-1.91e-01	-0.0228
55209	SETD5	A014-C-040	Human	Colorectum	FAP	2.12e-05	-1.59e-01	-0.1184
55209	SETD5	A002-C-201	Human	Colorectum	FAP	9.70e-14	-2.93e-01	0.0324
55209	SETD5	A001-C-119	Human	Colorectum	FAP	3.03e-06	-3.38e-01	-0.1557

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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:000647513	Esophagus	ESCC	internal protein amino acid acetylation	115/8552	160/18723	1.43e-11	5.08e-10	115
GO:00165735	Esophagus	ESCC	histone acetylation	110/8552	152/18723	1.95e-11	6.81e-10	110
GO:00434143	Esophagus	ESCC	macromolecule methylation	199/8552	316/18723	3.44e-10	9.57e-09	199
GO:003105614	Esophagus	ESCC	regulation of histone modification	106/8552	152/18723	1.52e-09	3.55e-08	106
GO:00322592	Esophagus	ESCC	methylation	222/8552	364/18723	2.26e-09	5.09e-08	222
GO:003278412	Esophagus	ESCC	regulation of DNA-templated transcription, elongation	45/8552	53/18723	3.64e-09	7.61e-08	45
GO:000632517	Esophagus	ESCC	chromatin organization	240/8552	409/18723	6.52e-08	1.14e-06	240
GO:000647914	Esophagus	ESCC	protein methylation	115/8552	181/18723	9.07e-07	1.16e-05	115
GO:000821314	Esophagus	ESCC	protein alkylation	115/8552	181/18723	9.07e-07	1.16e-05	115
GO:00165718	Esophagus	ESCC	histone methylation	89/8552	141/18723	2.17e-05	1.87e-04	89
GO:003496814	Esophagus	ESCC	histone lysine methylation	72/8552	115/18723	1.85e-04	1.18e-03	72
GO:20007564	Esophagus	ESCC	regulation of peptidyl-lysine acetylation	43/8552	63/18723	2.43e-04	1.50e-03	43
GO:003432918	Esophagus	ESCC	cell junction assembly	227/8552	420/18723	3.06e-04	1.83e-03	227
GO:001802214	Esophagus	ESCC	peptidyl-lysine methylation	79/8552	131/18723	5.17e-04	2.86e-03	79
GO:19019835	Esophagus	ESCC	regulation of protein acetylation	49/8552	77/18723	1.12e-03	5.60e-03	49
GO:00350653	Esophagus	ESCC	regulation of histone acetylation	36/8552	54/18723	1.49e-03	7.06e-03	36
GO:19022751	Esophagus	ESCC	regulation of chromatin organization	22/8552	33/18723	1.22e-02	4.08e-02	22
GO:00180231	Esophagus	ESCC	peptidyl-lysine trimethylation	31/8552	50/18723	1.48e-02	4.79e-02	31
GO:190188810	Esophagus	ESCC	regulation of cell junction assembly	109/8552	204/18723	1.53e-02	4.96e-02	109
GO:00165703	Liver	NAFLD	histone modification	90/1882	463/18723	5.74e-10	1.28e-07	90

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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

SETD5

SNV

Missense_Mutation

novel

c.572N>G

p.Ser191Cys

p.S191C

Q9C0A6

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-A2-A4S1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SETD5

SNV

Missense_Mutation

c.1130N>T

p.Ser377Phe

p.S377F

Q9C0A6

protein_coding

deleterious(0.01)

possibly_damaging(0.596)

TCGA-AN-A041-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SETD5

SNV

Missense_Mutation

c.1853N>A

p.Arg618Gln

p.R618Q

Q9C0A6

protein_coding

tolerated(0.07)

probably_damaging(0.988)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SETD5

SNV

Missense_Mutation

novel

c.2798N>T

p.Arg933Ile

p.R933I

Q9C0A6

protein_coding

tolerated(0.05)

benign(0.202)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SETD5

SNV

Missense_Mutation

c.2936N>T

p.Thr979Ile

p.T979I

Q9C0A6

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SETD5

SNV

Missense_Mutation

c.1079N>A

p.Val360Glu

p.V360E

Q9C0A6

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

SETD5

SNV

Missense_Mutation

novel

c.4180N>C

p.Ala1394Pro

p.A1394P

Q9C0A6

protein_coding

tolerated(0.49)

benign(0.001)

TCGA-AO-A0JM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SETD5

SNV

Missense_Mutation

c.2198C>A

p.Ala733Glu

p.A733E

Q9C0A6

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AR-A1AV-01

Breast

breast invasive carcinoma

Male

>=65

I/II

Chemotherapy

cytoxan

SETD5

SNV

Missense_Mutation

c.3980C>G

p.Ser1327Cys

p.S1327C

Q9C0A6

protein_coding

deleterious(0)

benign(0.001)

TCGA-BH-A0W7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

SETD5

SNV

Missense_Mutation

c.2377N>G

p.Met793Val

p.M793V

Q9C0A6

protein_coding

tolerated(0.23)

benign(0.16)

TCGA-BH-A1FL-01

Breast

breast invasive 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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