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:001943931	Oral cavity	NEOLP	aromatic compound catabolic process	75/2005	467/18723	2.22e-04	2.34e-03	75
GO:005077923	Oral cavity	NEOLP	RNA destabilization	21/2005	88/18723	3.17e-04	3.11e-03	21
GO:000008231	Oral cavity	NEOLP	G1/S transition of mitotic cell cycle	40/2005	214/18723	3.21e-04	3.11e-03	40
GO:190136131	Oral cavity	NEOLP	organic cyclic compound catabolic process	77/2005	495/18723	4.96e-04	4.40e-03	77
GO:004477231	Oral cavity	NEOLP	mitotic cell cycle phase transition	67/2005	424/18723	7.30e-04	5.98e-03	67
GO:004484331	Oral cavity	NEOLP	cell cycle G1/S phase transition	41/2005	241/18723	1.87e-03	1.28e-02	41
GO:00219532	Oral cavity	NEOLP	central nervous system neuron differentiation	30/2005	162/18723	1.96e-03	1.32e-02	30
GO:000734631	Oral cavity	NEOLP	regulation of mitotic cell cycle	69/2005	457/18723	2.07e-03	1.38e-02	69
GO:003526413	Oral cavity	NEOLP	multicellular organism growth	25/2005	132/18723	3.27e-03	1.95e-02	25
GO:004277031	Oral cavity	NEOLP	signal transduction in response to DNA damage	30/2005	172/18723	4.92e-03	2.67e-02	30
GO:00083441	Oral cavity	NEOLP	adult locomotory behavior	15/2005	71/18723	7.39e-03	3.73e-02	15
GO:200004531	Oral cavity	NEOLP	regulation of G1/S transition of mitotic cell cycle	25/2005	142/18723	8.58e-03	4.15e-02	25
GO:000641718	Prostate	BPH	regulation of translation	157/3107	468/18723	9.09e-20	5.63e-17	157
GO:190331116	Prostate	BPH	regulation of mRNA metabolic process	111/3107	288/18723	2.28e-19	1.17e-16	111
GO:000989618	Prostate	BPH	positive regulation of catabolic process	156/3107	492/18723	4.50e-17	1.11e-14	156
GO:003133118	Prostate	BPH	positive regulation of cellular catabolic process	135/3107	427/18723	7.82e-15	1.05e-12	135
GO:000640216	Prostate	BPH	mRNA catabolic process	84/3107	232/18723	3.25e-13	3.10e-11	84
GO:000640116	Prostate	BPH	RNA catabolic process	91/3107	278/18723	2.37e-11	1.60e-09	91
GO:006101314	Prostate	BPH	regulation of mRNA catabolic process	57/3107	166/18723	1.83e-08	5.69e-07	57
GO:004348814	Prostate	BPH	regulation of mRNA stability	54/3107	158/18723	5.13e-08	1.41e-06	54

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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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