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: AUTS2

Gene summary for AUTS2

Gene summary.

Gene information	Species	Human
	Gene symbol	AUTS2
	Gene ID	26053
	Gene name	activator of transcription and developmental regulator AUTS2
	Gene Alias	FBRSL2
	Cytomap	7q11.22
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q8WXX7

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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
26053	AUTS2	CA_HPV_3	Human	Cervix	CC	2.42e-03	6.60e-02	0.0414
26053	AUTS2	CCI_2	Human	Cervix	CC	2.38e-05	8.16e-01	0.5249
26053	AUTS2	CCI_3	Human	Cervix	CC	4.81e-27	1.44e+00	0.516
26053	AUTS2	T1	Human	Cervix	CC	7.26e-06	3.69e-01	0.0918
26053	AUTS2	HTA11_1938_2000001011	Human	Colorectum	AD	1.36e-06	5.31e-01	-0.0811
26053	AUTS2	HTA11_78_2000001011	Human	Colorectum	AD	2.18e-03	5.24e-01	-0.1088
26053	AUTS2	HTA11_347_2000001011	Human	Colorectum	AD	8.59e-15	6.74e-01	-0.1954
26053	AUTS2	HTA11_6818_2000001011	Human	Colorectum	AD	2.59e-05	7.23e-01	0.0112
26053	AUTS2	HTA11_6818_2000001021	Human	Colorectum	AD	7.40e-08	6.89e-01	0.0588
26053	AUTS2	HTA11_99999974143_84620	Human	Colorectum	MSS	9.45e-16	-5.47e-01	0.3005
26053	AUTS2	A015-C-203	Human	Colorectum	FAP	4.60e-23	-1.87e-01	-0.1294
26053	AUTS2	A015-C-204	Human	Colorectum	FAP	1.14e-02	-2.15e-01	-0.0228
26053	AUTS2	A002-C-201	Human	Colorectum	FAP	1.88e-08	-2.72e-01	0.0324
26053	AUTS2	A002-C-203	Human	Colorectum	FAP	1.63e-03	2.75e-01	0.2786
26053	AUTS2	A001-C-119	Human	Colorectum	FAP	2.97e-03	-3.70e-01	-0.1557
26053	AUTS2	A001-C-108	Human	Colorectum	FAP	1.15e-12	-5.55e-02	-0.0272
26053	AUTS2	A002-C-205	Human	Colorectum	FAP	1.54e-15	-1.55e-01	-0.1236
26053	AUTS2	A015-C-006	Human	Colorectum	FAP	8.08e-10	-3.04e-01	-0.0994
26053	AUTS2	A015-C-106	Human	Colorectum	FAP	2.66e-08	7.31e-03	-0.0511
26053	AUTS2	A002-C-114	Human	Colorectum	FAP	2.23e-15	-4.69e-01	-0.1561

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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:00072656	Cervix	CC	Ras protein signal transduction	79/2311	337/18723	9.49e-09	7.77e-07	79
GO:00975817	Cervix	CC	lamellipodium organization	31/2311	90/18723	4.57e-08	2.76e-06	31
GO:00300325	Cervix	CC	lamellipodium assembly	26/2311	72/18723	1.87e-07	8.48e-06	26
GO:00315328	Cervix	CC	actin cytoskeleton reorganization	31/2311	107/18723	3.34e-06	8.99e-05	31
GO:00313467	Cervix	CC	positive regulation of cell projection organization	72/2311	353/18723	1.04e-05	2.32e-04	72
GO:00160498	Cervix	CC	cell growth	92/2311	482/18723	1.16e-05	2.49e-04	92
GO:19027437	Cervix	CC	regulation of lamellipodium organization	19/2311	54/18723	1.27e-05	2.60e-04	19
GO:00615647	Cervix	CC	axon development	89/2311	467/18723	1.71e-05	3.27e-04	89
GO:00465785	Cervix	CC	regulation of Ras protein signal transduction	44/2311	189/18723	2.05e-05	3.73e-04	44
GO:19027457	Cervix	CC	positive regulation of lamellipodium organization	14/2311	37/18723	6.97e-05	9.81e-04	14
GO:00074097	Cervix	CC	axonogenesis	78/2311	418/18723	1.14e-04	1.43e-03	78
GO:00165705	Cervix	CC	histone modification	84/2311	463/18723	1.70e-04	2.01e-03	84
GO:00105916	Cervix	CC	regulation of lamellipodium assembly	14/2311	42/18723	3.32e-04	3.49e-03	14
GO:00105926	Cervix	CC	positive regulation of lamellipodium assembly	11/2311	29/18723	4.06e-04	4.15e-03	11
GO:00349685	Cervix	CC	histone lysine methylation	27/2311	115/18723	6.61e-04	6.09e-03	27
GO:00310565	Cervix	CC	regulation of histone modification	33/2311	152/18723	7.97e-04	7.00e-03	33
GO:00605606	Cervix	CC	developmental growth involved in morphogenesis	46/2311	234/18723	8.82e-04	7.63e-03	46
GO:01200328	Cervix	CC	regulation of plasma membrane bounded cell projection assembly	38/2311	186/18723	1.14e-03	9.35e-03	38
GO:00604917	Cervix	CC	regulation of cell projection assembly	38/2311	188/18723	1.40e-03	1.10e-02	38

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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

AUTS2

SNV

Missense_Mutation

novel

c.3679C>A

p.Leu1227Met

p.L1227M

Q8WXX7

protein_coding

deleterious(0.05)

probably_damaging(0.998)

TCGA-A8-A09Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

AUTS2

SNV

Missense_Mutation

c.1429N>G

p.Leu477Val

p.L477V

Q8WXX7

protein_coding

deleterious(0)

benign(0.359)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AUTS2

SNV

Missense_Mutation

c.2284N>C

p.Gly762Arg

p.G762R

Q8WXX7

protein_coding

deleterious(0)

probably_damaging(0.942)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

AUTS2

SNV

Missense_Mutation

c.2285N>T

p.Gly762Val

p.G762V

Q8WXX7

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

AUTS2

SNV

Missense_Mutation

c.2335N>T

p.Asp779Tyr

p.D779Y

Q8WXX7

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-BH-A0DH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

AUTS2

SNV

Missense_Mutation

novel

c.3664C>G

p.Pro1222Ala

p.P1222A

Q8WXX7

protein_coding

deleterious(0)

probably_damaging(0.941)

TCGA-OL-A5RW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

AUTS2

insertion

Nonsense_Mutation

novel

c.2058_2059insTAGGCAGTTGTATCCAGCACTGCGGGCGGAAATGATTCCAT

p.Leu687Ter

p.L687*

Q8WXX7

protein_coding

TCGA-A8-A06Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AUTS2

SNV

Missense_Mutation

c.1549N>T

p.Pro517Ser

p.P517S

Q8WXX7

protein_coding

tolerated(0.21)

probably_damaging(0.93)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

AUTS2

SNV

Missense_Mutation

c.2674G>C

p.Glu892Gln

p.E892Q

Q8WXX7

protein_coding

deleterious(0.01)

possibly_damaging(0.542)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

AUTS2

SNV

Missense_Mutation

c.1150G>A

p.Ala384Thr

p.A384T

Q8WXX7

protein_coding

tolerated(0.29)

benign(0.001)

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

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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