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: URI1

Gene summary for URI1

Gene summary.

Gene information	Species	Human
	Gene symbol	URI1
	Gene ID	8725
	Gene name	URI1 prefoldin like chaperone
	Gene Alias	C19orf2
	Cytomap	19q12
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	O94763

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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
8725	URI1	CA_HPV_1	Human	Cervix	CC	3.74e-06	-1.47e-01	0.0264
8725	URI1	CCI_2	Human	Cervix	CC	6.99e-05	6.13e-01	0.5249
8725	URI1	L1	Human	Cervix	CC	2.92e-02	-1.44e-01	0.0802
8725	URI1	HTA11_3410_2000001011	Human	Colorectum	AD	9.56e-24	-7.07e-01	0.0155
8725	URI1	HTA11_2487_2000001011	Human	Colorectum	SER	1.19e-02	-4.60e-01	-0.1808
8725	URI1	HTA11_2951_2000001011	Human	Colorectum	AD	1.44e-02	-7.07e-01	0.0216
8725	URI1	HTA11_2112_2000001011	Human	Colorectum	SER	3.28e-03	-7.51e-01	-0.2196
8725	URI1	HTA11_3361_2000001011	Human	Colorectum	AD	1.06e-05	-5.31e-01	-0.1207
8725	URI1	HTA11_696_2000001011	Human	Colorectum	AD	9.28e-10	-4.59e-01	-0.1464
8725	URI1	HTA11_866_2000001011	Human	Colorectum	AD	2.38e-13	-5.25e-01	-0.1001
8725	URI1	HTA11_1391_2000001011	Human	Colorectum	AD	4.97e-02	-3.81e-01	-0.059
8725	URI1	HTA11_2992_2000001011	Human	Colorectum	SER	2.12e-03	-6.43e-01	-0.1706
8725	URI1	HTA11_5212_2000001011	Human	Colorectum	AD	1.54e-07	-8.30e-01	-0.2061
8725	URI1	HTA11_546_2000001011	Human	Colorectum	AD	4.75e-03	-5.42e-01	-0.0842
8725	URI1	HTA11_9341_2000001011	Human	Colorectum	SER	7.68e-03	-8.39e-01	-0.00410000000000005
8725	URI1	HTA11_866_3004761011	Human	Colorectum	AD	6.31e-09	-5.10e-01	0.096
8725	URI1	HTA11_8622_2000001021	Human	Colorectum	SER	1.13e-04	-6.42e-01	0.0528
8725	URI1	HTA11_10711_2000001011	Human	Colorectum	AD	1.77e-07	-5.67e-01	0.0338
8725	URI1	HTA11_7696_3000711011	Human	Colorectum	AD	3.48e-03	-3.34e-01	0.0674
8725	URI1	HTA11_6818_2000001011	Human	Colorectum	AD	5.71e-03	-5.86e-01	0.0112

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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:200124328	Thyroid	HT	negative regulation of intrinsic apoptotic signaling pathway	20/1272	98/18723	7.87e-06	2.23e-04	20
GO:001604926	Thyroid	HT	cell growth	58/1272	482/18723	1.56e-05	3.82e-04	58
GO:004593629	Thyroid	HT	negative regulation of phosphate metabolic process	54/1272	441/18723	1.86e-05	4.39e-04	54
GO:001056329	Thyroid	HT	negative regulation of phosphorus metabolic process	54/1272	442/18723	1.99e-05	4.60e-04	54
GO:000155825	Thyroid	HT	regulation of cell growth	47/1272	414/18723	3.77e-04	4.76e-03	47
GO:2001233113	Thyroid	PTC	regulation of apoptotic signaling pathway	197/5968	356/18723	2.58e-20	3.69e-18	197
GO:0097193113	Thyroid	PTC	intrinsic apoptotic signaling pathway	164/5968	288/18723	9.17e-19	1.09e-16	164
GO:0010563113	Thyroid	PTC	negative regulation of phosphorus metabolic process	219/5968	442/18723	4.47e-15	3.07e-13	219
GO:0045936113	Thyroid	PTC	negative regulation of phosphate metabolic process	218/5968	441/18723	7.08e-15	4.75e-13	218
GO:2001242113	Thyroid	PTC	regulation of intrinsic apoptotic signaling pathway	99/5968	164/18723	4.74e-14	2.79e-12	99
GO:2001234113	Thyroid	PTC	negative regulation of apoptotic signaling pathway	124/5968	224/18723	2.57e-13	1.32e-11	124
GO:0016049112	Thyroid	PTC	cell growth	225/5968	482/18723	4.75e-12	2.07e-10	225
GO:2001243113	Thyroid	PTC	negative regulation of intrinsic apoptotic signaling pathway	60/5968	98/18723	2.05e-09	5.77e-08	60
GO:0001558111	Thyroid	PTC	regulation of cell growth	188/5968	414/18723	4.13e-09	1.09e-07	188
GO:0048545113	Thyroid	PTC	response to steroid hormone	158/5968	339/18723	8.10e-09	2.00e-07	158
GO:000961520	Thyroid	PTC	response to virus	162/5968	367/18723	4.52e-07	7.41e-06	162
GO:0071383112	Thyroid	PTC	cellular response to steroid hormone stimulus	98/5968	204/18723	9.83e-07	1.47e-05	98
GO:003530324	Thyroid	PTC	regulation of dephosphorylation	67/5968	128/18723	1.19e-06	1.72e-05	67
GO:001631116	Thyroid	PTC	dephosphorylation	174/5968	417/18723	1.20e-05	1.31e-04	174
GO:001092116	Thyroid	PTC	regulation of phosphatase activity	44/5968	84/18723	7.53e-05	6.48e-04	44

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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

URI1

SNV

Missense_Mutation

novel

c.508N>A

p.Glu170Lys

p.E170K

O94763

protein_coding

tolerated(0.13)

benign(0.099)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

URI1

SNV

Missense_Mutation

c.1546N>A

p.Ser516Thr

p.S516T

O94763

protein_coding

tolerated(0.15)

benign(0.156)

TCGA-AN-A0XU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

URI1

SNV

Missense_Mutation

c.828A>T

p.Glu276Asp

p.E276D

O94763

protein_coding

tolerated_low_confidence(0.24)

benign(0)

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

URI1

deletion

Frame_Shift_Del

novel

c.1607delN

p.Ter536TrpfsTer14

p.*536Wfs*14

O94763

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

URI1

SNV

Missense_Mutation

novel

c.1516C>A

p.Pro506Thr

p.P506T

O94763

protein_coding

deleterious_low_confidence(0.03)

possibly_damaging(0.674)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

URI1

SNV

Missense_Mutation

rs769475335

c.638G>A

p.Arg213Gln

p.R213Q

O94763

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

URI1

SNV

Missense_Mutation

novel

c.878C>A

p.Ser293Tyr

p.S293Y

O94763

protein_coding

deleterious(0)

possibly_damaging(0.483)

TCGA-VS-A9UR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

URI1

SNV

Missense_Mutation

rs138648155

c.770N>T

p.Ala257Val

p.A257V

O94763

protein_coding

tolerated(0.64)

benign(0)

TCGA-AA-3821-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

URI1

SNV

Missense_Mutation

c.747N>T

p.Glu249Asp

p.E249D

O94763

protein_coding

tolerated(0.11)

probably_damaging(0.978)

TCGA-AD-6899-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

URI1

SNV

Missense_Mutation

novel

c.287N>C

p.Val96Ala

p.V96A

O94763

protein_coding

deleterious(0)

probably_damaging(0.913)

TCGA-AZ-4315-01

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

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