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: GIGYF2

Gene summary for GIGYF2

Gene summary.

Gene information	Species	Human
	Gene symbol	GIGYF2
	Gene ID	26058
	Gene name	GRB10 interacting GYF protein 2
	Gene Alias	GYF2
	Cytomap	2q37.1
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	Q6Y7W6

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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
26058	GIGYF2	HTA11_3410_2000001011	Human	Colorectum	AD	1.77e-19	-6.46e-01	0.0155
26058	GIGYF2	HTA11_2487_2000001011	Human	Colorectum	SER	1.47e-06	-5.41e-01	-0.1808
26058	GIGYF2	HTA11_2951_2000001011	Human	Colorectum	AD	4.14e-02	-7.21e-01	0.0216
26058	GIGYF2	HTA11_3361_2000001011	Human	Colorectum	AD	2.74e-05	-5.16e-01	-0.1207
26058	GIGYF2	HTA11_5212_2000001011	Human	Colorectum	AD	1.40e-03	-6.63e-01	-0.2061
26058	GIGYF2	HTA11_866_3004761011	Human	Colorectum	AD	4.07e-04	-3.72e-01	0.096
26058	GIGYF2	HTA11_10711_2000001011	Human	Colorectum	AD	7.91e-05	-5.23e-01	0.0338
26058	GIGYF2	HTA11_6818_2000001021	Human	Colorectum	AD	7.29e-08	-4.84e-01	0.0588
26058	GIGYF2	HTA11_99999970781_79442	Human	Colorectum	MSS	2.87e-09	-4.47e-01	0.294
26058	GIGYF2	HTA11_99999974143_84620	Human	Colorectum	MSS	4.64e-09	-4.26e-01	0.3005
26058	GIGYF2	A002-C-010	Human	Colorectum	FAP	4.19e-02	-1.85e-01	0.242
26058	GIGYF2	A001-C-207	Human	Colorectum	FAP	1.92e-04	-2.56e-01	0.1278
26058	GIGYF2	A015-C-203	Human	Colorectum	FAP	1.17e-30	-4.08e-01	-0.1294
26058	GIGYF2	A015-C-204	Human	Colorectum	FAP	4.42e-06	-2.54e-01	-0.0228
26058	GIGYF2	A014-C-040	Human	Colorectum	FAP	2.03e-08	-6.08e-01	-0.1184
26058	GIGYF2	A002-C-201	Human	Colorectum	FAP	2.83e-13	-2.75e-01	0.0324
26058	GIGYF2	A002-C-203	Human	Colorectum	FAP	1.10e-04	-1.81e-01	0.2786
26058	GIGYF2	A001-C-119	Human	Colorectum	FAP	8.65e-07	3.82e-02	-0.1557
26058	GIGYF2	A001-C-108	Human	Colorectum	FAP	1.05e-14	-1.28e-01	-0.0272
26058	GIGYF2	A002-C-205	Human	Colorectum	FAP	6.31e-25	-2.57e-01	-0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:006101325	Thyroid	ATC	regulation of mRNA catabolic process	95/6293	166/18723	3.27e-10	9.16e-09	95
GO:004348826	Thyroid	ATC	regulation of mRNA stability	90/6293	158/18723	1.31e-09	3.30e-08	90
GO:190198715	Thyroid	ATC	regulation of cell cycle phase transition	187/6293	390/18723	2.36e-09	5.61e-08	187
GO:004578614	Thyroid	ATC	negative regulation of cell cycle	181/6293	385/18723	2.64e-08	5.07e-07	181
GO:0048872210	Thyroid	ATC	homeostasis of number of cells	135/6293	272/18723	2.92e-08	5.50e-07	135
GO:0061157110	Thyroid	ATC	mRNA destabilization	52/6293	84/18723	1.01e-07	1.70e-06	52
GO:000979115	Thyroid	ATC	post-embryonic development	50/6293	80/18723	1.14e-07	1.92e-06	50
GO:190199115	Thyroid	ATC	negative regulation of mitotic cell cycle phase transition	94/6293	179/18723	1.33e-07	2.19e-06	94
GO:0061014110	Thyroid	ATC	positive regulation of mRNA catabolic process	53/6293	87/18723	1.63e-07	2.61e-06	53
GO:004593015	Thyroid	ATC	negative regulation of mitotic cell cycle	117/6293	235/18723	1.93e-07	3.05e-06	117
GO:004484316	Thyroid	ATC	cell cycle G1/S phase transition	119/6293	241/18723	2.68e-07	4.10e-06	119
GO:0050779110	Thyroid	ATC	RNA destabilization	53/6293	88/18723	2.75e-07	4.20e-06	53
GO:004277016	Thyroid	ATC	signal transduction in response to DNA damage	90/6293	172/18723	3.01e-07	4.52e-06	90
GO:000008216	Thyroid	ATC	G1/S transition of mitotic cell cycle	107/6293	214/18723	4.83e-07	6.99e-06	107
GO:000709312	Thyroid	ATC	mitotic cell cycle checkpoint	69/6293	129/18723	2.52e-06	2.96e-05	69
GO:000007513	Thyroid	ATC	cell cycle checkpoint	84/6293	169/18723	1.05e-05	1.04e-04	84
GO:001094813	Thyroid	ATC	negative regulation of cell cycle process	134/6293	294/18723	1.19e-05	1.15e-04	134
GO:190198813	Thyroid	ATC	negative regulation of cell cycle phase transition	116/6293	249/18723	1.33e-05	1.27e-04	116
GO:003424923	Thyroid	ATC	negative regulation of cellular amide metabolic process	121/6293	273/18723	1.36e-04	9.57e-04	121
GO:190280615	Thyroid	ATC	regulation of cell cycle G1/S phase transition	79/6293	168/18723	2.04e-04	1.35e-03	79

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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

GIGYF2

SNV

Missense_Mutation

novel

c.2206N>T

p.Asp736Tyr

p.D736Y

Q6Y7W6

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-A7-A4SF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

GIGYF2

SNV

Missense_Mutation

c.1021N>A

p.Glu341Lys

p.E341K

Q6Y7W6

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

GIGYF2

SNV

Missense_Mutation

rs372418931

c.3059N>T

p.Thr1020Met

p.T1020M

Q6Y7W6

protein_coding

tolerated(0.46)

benign(0.441)

TCGA-E2-A15C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

GIGYF2

insertion

Nonsense_Mutation

novel

c.3493_3494insTCTCCTGGGCTGGAATGTAGCTAGGACT

p.His1165LeufsTer7

p.H1165Lfs*7

Q6Y7W6

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

GIGYF2

deletion

Frame_Shift_Del

c.734delN

p.Ala245ValfsTer56

p.A245Vfs*56

Q6Y7W6

protein_coding

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GIGYF2

SNV

Missense_Mutation

c.3323N>A

p.Gly1108Glu

p.G1108E

Q6Y7W6

protein_coding

deleterious(0)

benign(0.015)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

GIGYF2

SNV

Missense_Mutation

c.712N>A

p.Glu238Lys

p.E238K

Q6Y7W6

protein_coding

tolerated(0.1)

possibly_damaging(0.776)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

GIGYF2

SNV

Missense_Mutation

rs754519471

c.2402N>A

p.Arg801Gln

p.R801Q

Q6Y7W6

protein_coding

tolerated(0.26)

benign(0.297)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GIGYF2

SNV

Missense_Mutation

novel

c.937N>A

p.Glu313Lys

p.E313K

Q6Y7W6

protein_coding

deleterious(0.01)

possibly_damaging(0.857)

TCGA-ZJ-AB0H-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

GIGYF2

SNV

Missense_Mutation

c.2423N>A

p.Arg808Gln

p.R808Q

Q6Y7W6

protein_coding

deleterious(0.01)

probably_damaging(0.953)

TCGA-AA-3672-01

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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