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: SOS1

Gene summary for SOS1

Gene summary.

Gene information	Species	Human
	Gene symbol	SOS1
	Gene ID	6654
	Gene name	SOS Ras/Rac guanine nucleotide exchange factor 1
	Gene Alias	GF1
	Cytomap	2p22.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q07889

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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
6654	SOS1	CCI_1	Human	Cervix	CC	1.84e-05	1.14e+00	0.528
6654	SOS1	CCI_2	Human	Cervix	CC	8.82e-14	1.52e+00	0.5249
6654	SOS1	CCI_3	Human	Cervix	CC	8.21e-15	9.67e-01	0.516
6654	SOS1	HTA11_3410_2000001011	Human	Colorectum	AD	1.20e-24	-6.35e-01	0.0155
6654	SOS1	HTA11_2951_2000001011	Human	Colorectum	AD	5.97e-05	-6.82e-01	0.0216
6654	SOS1	HTA11_347_2000001011	Human	Colorectum	AD	6.65e-03	4.39e-01	-0.1954
6654	SOS1	HTA11_3361_2000001011	Human	Colorectum	AD	3.96e-02	-4.07e-01	-0.1207
6654	SOS1	HTA11_9408_2000001011	Human	Colorectum	AD	3.04e-02	-6.04e-01	0.0451
6654	SOS1	HTA11_8622_2000001021	Human	Colorectum	SER	1.00e-04	-3.24e-01	0.0528
6654	SOS1	HTA11_99999970781_79442	Human	Colorectum	MSS	3.22e-02	-2.04e-01	0.294
6654	SOS1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.48e-03	7.77e-01	0.3487
6654	SOS1	HTA11_99999974143_84620	Human	Colorectum	MSS	2.83e-07	-3.96e-01	0.3005
6654	SOS1	F007	Human	Colorectum	FAP	4.05e-02	-2.61e-01	0.1176
6654	SOS1	A001-C-207	Human	Colorectum	FAP	4.50e-05	-2.67e-01	0.1278
6654	SOS1	A015-C-203	Human	Colorectum	FAP	1.40e-37	-5.92e-01	-0.1294
6654	SOS1	A015-C-204	Human	Colorectum	FAP	1.12e-11	-4.84e-01	-0.0228
6654	SOS1	A014-C-040	Human	Colorectum	FAP	1.71e-06	-4.92e-01	-0.1184
6654	SOS1	A002-C-201	Human	Colorectum	FAP	3.40e-22	-5.24e-01	0.0324
6654	SOS1	A001-C-119	Human	Colorectum	FAP	3.30e-18	-7.46e-01	-0.1557
6654	SOS1	A001-C-108	Human	Colorectum	FAP	1.95e-23	-4.59e-01	-0.0272

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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
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:00085446	Cervix	CC	epidermis development	83/2311	324/18723	3.91e-11	8.54e-09	83
GO:00435884	Cervix	CC	skin development	71/2311	263/18723	8.04e-11	1.46e-08	71
GO:00421108	Cervix	CC	T cell activation	107/2311	487/18723	1.24e-09	1.46e-07	107
GO:00508638	Cervix	CC	regulation of T cell activation	80/2311	329/18723	1.28e-09	1.47e-07	80
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:00071738	Cervix	CC	epidermal growth factor receptor signaling pathway	36/2311	108/18723	1.04e-08	8.44e-07	36
GO:00381278	Cervix	CC	ERBB signaling pathway	37/2311	121/18723	8.57e-08	4.88e-06	37
GO:00027644	Cervix	CC	immune response-regulating signaling pathway	97/2311	468/18723	1.49e-07	7.07e-06	97
GO:190370610	Cervix	CC	regulation of hemopoiesis	80/2311	367/18723	2.14e-07	9.55e-06	80
GO:00509007	Cervix	CC	leukocyte migration	78/2311	369/18723	1.09e-06	3.80e-05	78
GO:00420988	Cervix	CC	T cell proliferation	49/2311	199/18723	1.32e-06	4.49e-05	49
GO:00020111	Cervix	CC	morphogenesis of an epithelial sheet	21/2311	57/18723	1.91e-06	5.97e-05	21
GO:004887210	Cervix	CC	homeostasis of number of cells	61/2311	272/18723	2.17e-06	6.55e-05	61
GO:00421297	Cervix	CC	regulation of T cell proliferation	43/2311	171/18723	3.21e-06	8.77e-05	43
GO:00380933	Cervix	CC	Fc receptor signaling pathway	19/2311	50/18723	3.42e-06	9.17e-05	19
GO:19021056	Cervix	CC	regulation of leukocyte differentiation	61/2311	279/18723	5.16e-06	1.29e-04	61
GO:00706637	Cervix	CC	regulation of leukocyte proliferation	55/2311	245/18723	6.51e-06	1.56e-04	55
GO:00506705	Cervix	CC	regulation of lymphocyte proliferation	51/2311	225/18723	1.05e-05	2.32e-04	51
GO:00329444	Cervix	CC	regulation of mononuclear cell proliferation	51/2311	227/18723	1.36e-05	2.73e-04	51

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0451024	Endometrium	EEC	Focal adhesion	58/1237	203/8465	1.61e-07	2.30e-06	1.71e-06	58
hsa0520524	Endometrium	EEC	Proteoglycans in cancer	52/1237	205/8465	3.01e-05	3.19e-04	2.38e-04	52
hsa0491526	Endometrium	EEC	Estrogen signaling pathway	34/1237	138/8465	1.19e-03	8.02e-03	5.98e-03	34
hsa0472222	Endometrium	EEC	Neurotrophin signaling pathway	30/1237	119/8465	1.54e-03	9.55e-03	7.12e-03	30
hsa0521522	Endometrium	EEC	Prostate cancer	25/1237	97/8465	2.66e-03	1.56e-02	1.16e-02	25
hsa0521323	Endometrium	EEC	Endometrial cancer	17/1237	58/8465	2.97e-03	1.71e-02	1.28e-02	17
hsa0481024	Endometrium	EEC	Regulation of actin cytoskeleton	49/1237	229/8465	3.20e-03	1.78e-02	1.33e-02	49
hsa0516325	Endometrium	EEC	Human cytomegalovirus infection	47/1237	225/8465	6.17e-03	3.12e-02	2.33e-02	47
hsa0520836	Endometrium	EEC	Chemical carcinogenesis - reactive oxygen species	94/1237	223/8465	4.11e-24	1.93e-22	1.44e-22	94
hsa0471436	Endometrium	EEC	Thermogenesis	85/1237	232/8465	2.79e-17	7.05e-16	5.26e-16	85
hsa0451034	Endometrium	EEC	Focal adhesion	58/1237	203/8465	1.61e-07	2.30e-06	1.71e-06	58
hsa0520534	Endometrium	EEC	Proteoglycans in cancer	52/1237	205/8465	3.01e-05	3.19e-04	2.38e-04	52
hsa0491535	Endometrium	EEC	Estrogen signaling pathway	34/1237	138/8465	1.19e-03	8.02e-03	5.98e-03	34
hsa0472232	Endometrium	EEC	Neurotrophin signaling pathway	30/1237	119/8465	1.54e-03	9.55e-03	7.12e-03	30
hsa0521532	Endometrium	EEC	Prostate cancer	25/1237	97/8465	2.66e-03	1.56e-02	1.16e-02	25
hsa0521333	Endometrium	EEC	Endometrial cancer	17/1237	58/8465	2.97e-03	1.71e-02	1.28e-02	17
hsa0481034	Endometrium	EEC	Regulation of actin cytoskeleton	49/1237	229/8465	3.20e-03	1.78e-02	1.33e-02	49
hsa0516335	Endometrium	EEC	Human cytomegalovirus infection	47/1237	225/8465	6.17e-03	3.12e-02	2.33e-02	47
hsa0481010	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa04068	Liver	NAFLD	FoxO signaling pathway	30/1043	131/8465	4.91e-04	8.05e-03	6.49e-03	30

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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

SOS1

SNV

Missense_Mutation

c.598A>G

p.Thr200Ala

p.T200A

Q07889

protein_coding

tolerated(0.09)

benign(0)

TCGA-A2-A0SX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SOS1

SNV

Missense_Mutation

novel

c.1468C>A

p.Leu490Ile

p.L490I

Q07889

protein_coding

deleterious(0.01)

probably_damaging(0.989)

TCGA-A8-A085-01

Breast

breast invasive carcinoma

Male

<65

I/II

Hormone Therapy

tamoxiphen

SOS1

SNV

Missense_Mutation

rs727505383

c.3433G>A

p.Asp1145Asn

p.D1145N

Q07889

protein_coding

deleterious(0.03)

benign(0.053)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SOS1

SNV

Missense_Mutation

c.1846N>T

p.His616Tyr

p.H616Y

Q07889

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E2-A14W-01

Breast

breast invasive carcinoma

Male

>=65

I/II

Chemotherapy

cytoxan

SOS1

insertion

Nonsense_Mutation

novel

c.517_518insACTGTAGCCACACAGCCATAAATGACTGATAAGAGAAACAGTG

p.Met173AsnfsTer10

p.M173Nfs*10

Q07889

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SOS1

insertion

Frame_Shift_Ins

novel

c.3688_3689insAAAAGAT

p.Pro1230GlnfsTer16

p.P1230Qfs*16

Q07889

protein_coding

TCGA-AR-A0TU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Doxorubicin

SOS1

deletion

Frame_Shift_Del

novel

c.2848delN

p.Arg950AspfsTer7

p.R950Dfs*7

Q07889

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

SOS1

SNV

Missense_Mutation

novel

c.451A>C

p.Asn151His

p.N151H

Q07889

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SOS1

SNV

Missense_Mutation

rs371408734

c.3709N>G

p.Pro1237Ala

p.P1237A

Q07889

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.986)

TCGA-C5-A7CO-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

SOS1

SNV

Missense_Mutation

novel

c.3150N>A

p.Met1050Ile

p.M1050I

Q07889

protein_coding

tolerated(0.18)

benign(0.048)

TCGA-C5-A8XH-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
6654	SOS1	KINASE		385612239
6654	SOS1	KINASE		IL-6		9815779

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