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: ARHGEF10

Gene summary for ARHGEF10

Gene summary.

Gene information	Species	Human
	Gene symbol	ARHGEF10
	Gene ID	9639
	Gene name	Rho guanine nucleotide exchange factor 10
	Gene Alias	GEF10
	Cytomap	8p23.3
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	O15013

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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
9639	ARHGEF10	PTC01	Human	Thyroid	PTC	2.94e-09	1.79e-01	0.1899
9639	ARHGEF10	PTC04	Human	Thyroid	PTC	2.72e-08	1.80e-01	0.1927
9639	ARHGEF10	PTC05	Human	Thyroid	PTC	2.27e-12	3.97e-01	0.2065
9639	ARHGEF10	PTC06	Human	Thyroid	PTC	1.04e-09	3.11e-01	0.2057
9639	ARHGEF10	PTC07	Human	Thyroid	PTC	3.43e-13	2.35e-01	0.2044
9639	ARHGEF10	ATC11	Human	Thyroid	ATC	3.71e-05	3.62e-01	0.3386
9639	ARHGEF10	ATC12	Human	Thyroid	ATC	1.03e-18	3.27e-01	0.34
9639	ARHGEF10	ATC13	Human	Thyroid	ATC	9.67e-16	2.86e-01	0.34
9639	ARHGEF10	ATC2	Human	Thyroid	ATC	5.90e-10	7.12e-01	0.34
9639	ARHGEF10	ATC3	Human	Thyroid	ATC	4.97e-10	5.12e-01	0.338
9639	ARHGEF10	ATC4	Human	Thyroid	ATC	3.44e-20	3.71e-01	0.34
9639	ARHGEF10	ATC5	Human	Thyroid	ATC	6.75e-20	3.08e-01	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:01100534	Colorectum	FAP	regulation of actin filament organization	75/2622	278/18723	8.11e-09	1.10e-06	75
GO:00329564	Colorectum	FAP	regulation of actin cytoskeleton organization	90/2622	358/18723	1.20e-08	1.39e-06	90
GO:00510562	Colorectum	FAP	regulation of small GTPase mediated signal transduction	78/2622	302/18723	3.25e-08	2.85e-06	78
GO:00615723	Colorectum	FAP	actin filament bundle organization	49/2622	161/18723	5.69e-08	4.30e-06	49
GO:00510173	Colorectum	FAP	actin filament bundle assembly	48/2622	157/18723	6.62e-08	4.56e-06	48
GO:19029034	Colorectum	FAP	regulation of supramolecular fiber organization	92/2622	383/18723	8.48e-08	5.77e-06	92
GO:19029054	Colorectum	FAP	positive regulation of supramolecular fiber organization	57/2622	209/18723	3.28e-07	1.83e-05	57
GO:00514954	Colorectum	FAP	positive regulation of cytoskeleton organization	60/2622	226/18723	4.45e-07	2.37e-05	60
GO:00310323	Colorectum	FAP	actomyosin structure organization	51/2622	196/18723	5.89e-06	1.88e-04	51
GO:00322313	Colorectum	FAP	regulation of actin filament bundle assembly	30/2622	105/18723	7.54e-05	1.37e-03	30
GO:00069843	Colorectum	FAP	ER-nucleus signaling pathway	17/2622	46/18723	8.85e-05	1.57e-03	17
GO:00300383	Colorectum	FAP	contractile actin filament bundle assembly	30/2622	106/18723	9.12e-05	1.59e-03	30
GO:00431493	Colorectum	FAP	stress fiber assembly	30/2622	106/18723	9.12e-05	1.59e-03	30
GO:01100203	Colorectum	FAP	regulation of actomyosin structure organization	28/2622	100/18723	1.88e-04	2.76e-03	28
GO:00514922	Colorectum	FAP	regulation of stress fiber assembly	25/2622	91/18723	5.55e-04	6.22e-03	25
GO:00322333	Colorectum	FAP	positive regulation of actin filament bundle assembly	18/2622	63/18723	1.95e-03	1.65e-02	18
GO:00070155	Colorectum	CRC	actin filament organization	104/2078	442/18723	4.75e-14	7.12e-11	104
GO:00329705	Colorectum	CRC	regulation of actin filament-based process	89/2078	397/18723	5.25e-11	3.14e-08	89
GO:00510563	Colorectum	CRC	regulation of small GTPase mediated signal transduction	69/2078	302/18723	3.34e-09	9.08e-07	69
GO:19029035	Colorectum	CRC	regulation of supramolecular fiber organization	80/2078	383/18723	1.52e-08	2.75e-06	80

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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

ARHGEF10

SNV

Missense_Mutation

rs768961111

c.1621N>C

p.Glu541Gln

p.E541Q

O15013

protein_coding

deleterious(0)

possibly_damaging(0.843)

TCGA-A2-A0SY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

arimidex

ARHGEF10

SNV

Missense_Mutation

c.464N>A

p.Cys155Tyr

p.C155Y

O15013

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.93)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARHGEF10

SNV

Missense_Mutation

rs201516531

c.4039C>T

p.Arg1347Trp

p.R1347W

O15013

protein_coding

deleterious(0)

possibly_damaging(0.9)

TCGA-AC-A23C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

chemo

ARHGEF10

SNV

Missense_Mutation

novel

c.2893N>A

p.Glu965Lys

p.E965K

O15013

protein_coding

tolerated(0.12)

benign(0.418)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARHGEF10

SNV

Missense_Mutation

c.203N>A

p.Arg68Lys

p.R68K

O15013

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.648)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARHGEF10

insertion

Nonsense_Mutation

novel

c.2017_2018insGTTATTGCATCTAATATTCATTAT

p.Met673delinsSerTyrCysIleTerTyrSerLeuLeu

p.M673delinsSYCI*YSLL

O15013

protein_coding

TCGA-A2-A0CM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ARHGEF10

insertion

In_Frame_Ins

novel

c.1135_1136insGGATCACATATAATACCATAAATGGGG

p.Ser379delinsTrpIleThrTyrAsnThrIleAsnGlyAla

p.S379delinsWITYNTINGA

O15013

protein_coding

TCGA-AN-A0FL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ARHGEF10

SNV

Missense_Mutation

rs756284082

c.2498N>T

p.Thr833Met

p.T833M

O15013

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ARHGEF10

SNV

Missense_Mutation

novel

c.2948G>C

p.Arg983Thr

p.R983T

O15013

protein_coding

tolerated(0.21)

benign(0.164)

TCGA-VS-A954-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

ARHGEF10

SNV

Missense_Mutation

rs139046783

c.1048N>A

p.Val350Met

p.V350M

O15013

protein_coding

tolerated(1)

benign(0.04)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

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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