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: SOX5

Gene summary for SOX5

Gene summary.

Gene information	Species	Human
	Gene symbol	SOX5
	Gene ID	6660
	Gene name	SRY-box transcription factor 5
	Gene Alias	L-SOX5
	Cytomap	12p12.1
	Gene Type	protein-coding
	GO ID	GO:0001501
	UniProtAcc	P35711

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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
6660	SOX5	AEH-subject1	Human	Endometrium	AEH	1.03e-97	1.54e+00	-0.3059
6660	SOX5	AEH-subject2	Human	Endometrium	AEH	2.20e-46	1.21e+00	-0.2525
6660	SOX5	AEH-subject3	Human	Endometrium	AEH	1.41e-84	1.46e+00	-0.2576
6660	SOX5	AEH-subject4	Human	Endometrium	AEH	1.69e-52	1.31e+00	-0.2657
6660	SOX5	AEH-subject5	Human	Endometrium	AEH	7.87e-42	1.04e+00	-0.2953
6660	SOX5	EEC-subject1	Human	Endometrium	EEC	7.77e-84	1.42e+00	-0.2682
6660	SOX5	EEC-subject2	Human	Endometrium	EEC	1.74e-71	1.34e+00	-0.2607
6660	SOX5	EEC-subject3	Human	Endometrium	EEC	1.54e-05	3.23e-01	-0.2525
6660	SOX5	EEC-subject4	Human	Endometrium	EEC	5.09e-38	9.85e-01	-0.2571
6660	SOX5	EEC-subject5	Human	Endometrium	EEC	7.80e-19	6.35e-01	-0.249
6660	SOX5	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	7.00e-03	-3.35e-02	-0.1869
6660	SOX5	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	5.26e-04	-7.45e-03	-0.1917
6660	SOX5	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	1.03e-05	-6.09e-02	-0.1916
6660	SOX5	NAFLD1	Human	Liver	NAFLD	6.52e-17	1.57e+00	-0.04
6660	SOX5	S41	Human	Liver	Cirrhotic	3.22e-09	1.05e+00	-0.0343
6660	SOX5	HCC1_Meng	Human	Liver	HCC	2.08e-83	-3.79e-01	0.0246
6660	SOX5	HCC2_Meng	Human	Liver	HCC	6.90e-13	-4.94e-01	0.0107
6660	SOX5	cirrhotic1	Human	Liver	Cirrhotic	2.00e-11	-4.84e-01	0.0202
6660	SOX5	cirrhotic2	Human	Liver	Cirrhotic	7.07e-13	-4.92e-01	0.0201
6660	SOX5	cirrhotic3	Human	Liver	Cirrhotic	8.33e-08	-4.82e-01	0.0215

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:00715596	Endometrium	AEH	response to transforming growth factor beta	53/2100	256/18723	7.01e-06	1.69e-04	53
GO:00715606	Endometrium	AEH	cellular response to transforming growth factor beta stimulus	51/2100	250/18723	1.59e-05	3.32e-04	51
GO:00488635	Endometrium	AEH	stem cell differentiation	40/2100	206/18723	3.67e-04	3.99e-03	40
GO:0061448	Endometrium	AEH	connective tissue development	44/2100	252/18723	1.92e-03	1.51e-02	44
GO:007155914	Endometrium	EEC	response to transforming growth factor beta	54/2168	256/18723	8.25e-06	1.83e-04	54
GO:007156014	Endometrium	EEC	cellular response to transforming growth factor beta stimulus	52/2168	250/18723	1.81e-05	3.41e-04	52
GO:004886314	Endometrium	EEC	stem cell differentiation	43/2168	206/18723	8.48e-05	1.21e-03	43
GO:00613511	Endometrium	EEC	neural precursor cell proliferation	29/2168	145/18723	2.24e-03	1.67e-02	29
GO:00614481	Endometrium	EEC	connective tissue development	44/2168	252/18723	3.51e-03	2.36e-02	44
GO:00715593	Liver	NAFLD	response to transforming growth factor beta	51/1882	256/18723	1.43e-06	6.58e-05	51
GO:00715603	Liver	NAFLD	cellular response to transforming growth factor beta stimulus	48/1882	250/18723	8.27e-06	2.76e-04	48
GO:2000736	Liver	NAFLD	regulation of stem cell differentiation	14/1882	58/18723	1.48e-03	1.64e-02	14
GO:00488632	Liver	NAFLD	stem cell differentiation	33/1882	206/18723	4.81e-03	3.81e-02	33
GO:007155911	Liver	Cirrhotic	response to transforming growth factor beta	96/4634	256/18723	3.55e-06	6.09e-05	96
GO:007156011	Liver	Cirrhotic	cellular response to transforming growth factor beta stimulus	93/4634	250/18723	7.34e-06	1.13e-04	93
GO:20007361	Liver	Cirrhotic	regulation of stem cell differentiation	26/4634	58/18723	6.65e-04	5.04e-03	26
GO:0072497	Liver	Cirrhotic	mesenchymal stem cell differentiation	7/4634	11/18723	7.11e-03	3.41e-02	7
GO:004886311	Liver	Cirrhotic	stem cell differentiation	66/4634	206/18723	1.06e-02	4.68e-02	66
GO:007155921	Liver	HCC	response to transforming growth factor beta	141/7958	256/18723	3.08e-05	3.16e-04	141
GO:007156021	Liver	HCC	cellular response to transforming growth factor beta stimulus	137/7958	250/18723	5.47e-05	5.14e-04	137

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
SOX5	BAS	Cervix	CC	SNCAIP,TNFRSF18,RARRES1, etc.	1.32e-03
SOX5	COL	Cervix	CC	SNCAIP,TNFRSF18,RARRES1, etc.	5.09e-03
SOX5	COL	Cervix	N_HPV	SNCAIP,TNFRSF18,RARRES1, etc.	4.87e-01
SOX5	PLA	Cervix	CC	DENND5B,FUT8,PLCG2, etc.	2.61e-01
SOX5	BN	Cervix	CC	DENND5B,FUT8,PLCG2, etc.	9.13e-02
SOX5	TUF	Colorectum	AD	PCSK1N,LINC00907,GCG, etc.	9.45e-03
SOX5	EE	Colorectum	AD	PCSK1N,LINC00907,GCG, etc.	6.83e-02
SOX5	CT	Colorectum	AD	PCSK1N,LINC00907,GCG, etc.	1.21e-02
SOX5	SSC	Colorectum	AD	PCSK1N,LINC00907,GCG, etc.	-4.44e-16
SOX5	EE	Colorectum	ADJ	RIMBP2,PTPRN2,CACNA1C, etc.	1.84e-01

∗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

SOX5

SNV

Missense_Mutation

c.991N>T

p.Pro331Ser

p.P331S

P35711

protein_coding

tolerated(0.13)

probably_damaging(0.999)

TCGA-A8-A07B-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SOX5

SNV

Missense_Mutation

c.2099N>A

p.Ser700Asn

p.S700N

P35711

protein_coding

tolerated(0.14)

possibly_damaging(0.842)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SOX5

SNV

Missense_Mutation

c.1328G>C

p.Arg443Thr

p.R443T

P35711

protein_coding

tolerated(0.3)

probably_damaging(0.998)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

SOX5

SNV

Missense_Mutation

c.1213N>A

p.Asp405Asn

p.D405N

P35711

protein_coding

deleterious(0.01)

benign(0.131)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SOX5

insertion

Nonsense_Mutation

novel

c.1835_1836insATAA

p.Ser613Ter

p.S613*

P35711

protein_coding

TCGA-A7-A26I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

SOX5

insertion

In_Frame_Ins

novel

c.1835_1836insTAAGTATAA

p.Leu612_Ser613insLysTyrAsn

p.L612_S613insKYN

P35711

protein_coding

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SOX5

insertion

Frame_Shift_Ins

novel

c.73_74insTTCTT

p.Glu25ValfsTer8

p.E25Vfs*8

P35711

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SOX5

insertion

Frame_Shift_Ins

novel

c.2199_2200insCCAGCCAGGCTGGTCTCGAACTCCTGGGC

p.Glu734ProfsTer25

p.E734Pfs*25

P35711

protein_coding

TCGA-BH-A0BV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

SOX5

SNV

Missense_Mutation

novel

c.1970N>A

p.Arg657Gln

p.R657Q

P35711

protein_coding

deleterious(0.02)

probably_damaging(0.973)

TCGA-C5-A7UI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SOX5

SNV

Missense_Mutation

c.214N>G

p.Leu72Val

p.L72V

P35711

protein_coding

tolerated_low_confidence(0.34)

benign(0.028)

TCGA-EK-A3GM-01

Cervix

cervical & endocervical cancer

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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