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: TRIO

Gene summary for TRIO

Gene summary.

Gene information	Species	Human
	Gene symbol	TRIO
	Gene ID	7204
	Gene name	trio Rho guanine nucleotide exchange factor
	Gene Alias	ARHGEF23
	Cytomap	5p15.2
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	O75962

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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
7204	TRIO	CCI_1	Human	Cervix	CC	5.17e-17	1.46e+00	0.528
7204	TRIO	CCI_2	Human	Cervix	CC	5.32e-14	1.68e+00	0.5249
7204	TRIO	CCI_3	Human	Cervix	CC	1.84e-20	1.43e+00	0.516
7204	TRIO	CCII_1	Human	Cervix	CC	7.42e-05	4.93e-01	0.3249
7204	TRIO	HTA11_3410_2000001011	Human	Colorectum	AD	7.88e-11	-3.83e-01	0.0155
7204	TRIO	HTA11_2487_2000001011	Human	Colorectum	SER	3.20e-05	-4.34e-01	-0.1808
7204	TRIO	HTA11_347_2000001011	Human	Colorectum	AD	6.55e-08	5.41e-01	-0.1954
7204	TRIO	HTA11_7663_2000001011	Human	Colorectum	SER	7.90e-04	6.52e-01	0.0131
7204	TRIO	HTA11_6801_2000001011	Human	Colorectum	SER	4.21e-03	2.43e-01	0.0171
7204	TRIO	HTA11_6818_2000001021	Human	Colorectum	AD	9.96e-05	5.12e-01	0.0588
7204	TRIO	HTA11_99999965104_69814	Human	Colorectum	MSS	7.47e-06	5.18e-01	0.281
7204	TRIO	HTA11_99999971662_82457	Human	Colorectum	MSS	4.51e-06	6.49e-01	0.3859
7204	TRIO	HTA11_99999974143_84620	Human	Colorectum	MSS	1.83e-04	-3.28e-01	0.3005
7204	TRIO	A015-C-203	Human	Colorectum	FAP	3.69e-30	-5.52e-01	-0.1294
7204	TRIO	A015-C-204	Human	Colorectum	FAP	4.60e-03	-2.52e-01	-0.0228
7204	TRIO	A014-C-040	Human	Colorectum	FAP	4.85e-02	-1.67e-01	-0.1184
7204	TRIO	A002-C-201	Human	Colorectum	FAP	7.52e-16	-4.33e-01	0.0324
7204	TRIO	A001-C-119	Human	Colorectum	FAP	4.33e-09	-4.61e-01	-0.1557
7204	TRIO	A001-C-108	Human	Colorectum	FAP	1.38e-11	-3.11e-01	-0.0272
7204	TRIO	A002-C-205	Human	Colorectum	FAP	3.95e-30	-5.90e-01	-0.1236

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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:00510566	Cervix	CC	regulation of small GTPase mediated signal transduction	75/2311	302/18723	1.54e-09	1.74e-07	75
GO:00454445	Cervix	CC	fat cell differentiation	53/2311	229/18723	3.72e-06	9.75e-05	53
GO:00615647	Cervix	CC	axon development	89/2311	467/18723	1.71e-05	3.27e-04	89
GO:00074097	Cervix	CC	axonogenesis	78/2311	418/18723	1.14e-04	1.43e-03	78
GO:0045598	Cervix	CC	regulation of fat cell differentiation	31/2311	139/18723	7.06e-04	6.41e-03	31
GO:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0032535	Colorectum	AD	regulation of cellular component size	142/3918	383/18723	1.74e-13	3.41e-11	142
GO:1902903	Colorectum	AD	regulation of supramolecular fiber organization	139/3918	383/18723	2.01e-12	3.19e-10	139
GO:0032970	Colorectum	AD	regulation of actin filament-based process	142/3918	397/18723	4.05e-12	5.90e-10	142
GO:0110053	Colorectum	AD	regulation of actin filament organization	108/3918	278/18723	5.02e-12	6.98e-10	108
GO:0008154	Colorectum	AD	actin polymerization or depolymerization	90/3918	218/18723	6.14e-12	8.23e-10	90
GO:0032271	Colorectum	AD	regulation of protein polymerization	94/3918	233/18723	1.01e-11	1.29e-09	94
GO:0030041	Colorectum	AD	actin filament polymerization	81/3918	191/18723	1.35e-11	1.69e-09	81
GO:0051258	Colorectum	AD	protein polymerization	112/3918	297/18723	1.85e-11	2.27e-09	112
GO:0043254	Colorectum	AD	regulation of protein-containing complex assembly	148/3918	428/18723	2.64e-11	3.18e-09	148
GO:0002064	Colorectum	AD	epithelial cell development	89/3918	220/18723	2.98e-11	3.52e-09	89
GO:0008064	Colorectum	AD	regulation of actin polymerization or depolymerization	79/3918	188/18723	4.17e-11	4.74e-09	79
GO:0030833	Colorectum	AD	regulation of actin filament polymerization	74/3918	172/18723	4.50e-11	5.03e-09	74
GO:0030832	Colorectum	AD	regulation of actin filament length	79/3918	189/18723	5.71e-11	6.27e-09	79
GO:0032956	Colorectum	AD	regulation of actin cytoskeleton organization	127/3918	358/18723	1.03e-10	1.04e-08	127

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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

TRIO

SNV

Missense_Mutation

novel

c.1400N>A

p.Ala467Asp

p.A467D

O75962

protein_coding

tolerated(0.06)

probably_damaging(0.994)

TCGA-A2-A0YD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TRIO

SNV

Missense_Mutation

c.2092N>A

p.Val698Met

p.V698M

O75962

protein_coding

deleterious(0.02)

probably_damaging(0.988)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIO

SNV

Missense_Mutation

c.1510N>T

p.Asp504Tyr

p.D504Y

O75962

protein_coding

deleterious(0)

possibly_damaging(0.879)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TRIO

SNV

Missense_Mutation

c.2122N>C

p.Asp708His

p.D708H

O75962

protein_coding

tolerated(0.09)

benign(0.264)

TCGA-AC-A23C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

chemo

TRIO

SNV

Missense_Mutation

novel

c.4505N>A

p.Arg1502Gln

p.R1502Q

O75962

protein_coding

deleterious(0)

probably_damaging(0.929)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIO

SNV

Missense_Mutation

novel

c.6510N>A

p.Phe2170Leu

p.F2170L

O75962

protein_coding

tolerated(0.49)

benign(0.003)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIO

SNV

Missense_Mutation

c.5972N>C

p.Val1991Ala

p.V1991A

O75962

protein_coding

deleterious(0)

possibly_damaging(0.474)

TCGA-AR-A1AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

TRIO

SNV

Missense_Mutation

c.8319N>A

p.Ser2773Arg

p.S2773R

O75962

protein_coding

tolerated(0.05)

probably_damaging(0.978)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

TRIO

SNV

Missense_Mutation

rs748327260

c.8629N>T

p.Leu2877Phe

p.L2877F

O75962

protein_coding

tolerated(0.07)

probably_damaging(0.962)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

TRIO

SNV

Missense_Mutation

c.8104N>C

p.Val2702Leu

p.V2702L

O75962

protein_coding

tolerated(0.07)

possibly_damaging(0.903)

TCGA-BH-A18V-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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