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: GPT2

Gene summary for GPT2

Gene summary.

Gene information	Species	Human
	Gene symbol	GPT2
	Gene ID	84706
	Gene name	glutamic--pyruvic transaminase 2
	Gene Alias	ALT2
	Cytomap	16q11.2
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	Q8TD30

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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
84706	GPT2	NAFLD1	Human	Liver	NAFLD	2.02e-10	6.87e-01	-0.04
84706	GPT2	S41	Human	Liver	Cirrhotic	1.23e-07	8.43e-01	-0.0343
84706	GPT2	S43	Human	Liver	Cirrhotic	1.76e-08	-8.70e-02	-0.0187
84706	GPT2	HCC1_Meng	Human	Liver	HCC	3.39e-44	-8.78e-02	0.0246
84706	GPT2	HCC2_Meng	Human	Liver	HCC	8.17e-22	-3.74e-02	0.0107
84706	GPT2	cirrhotic1	Human	Liver	Cirrhotic	1.84e-02	-1.46e-01	0.0202
84706	GPT2	cirrhotic2	Human	Liver	Cirrhotic	2.32e-04	-1.61e-01	0.0201
84706	GPT2	HCC1	Human	Liver	HCC	1.54e-02	3.80e+00	0.5336
84706	GPT2	HCC2	Human	Liver	HCC	3.55e-15	4.22e+00	0.5341
84706	GPT2	Pt13.b	Human	Liver	HCC	4.14e-04	-6.06e-02	0.0251
84706	GPT2	S028	Human	Liver	HCC	1.34e-19	7.84e-01	0.2503
84706	GPT2	S029	Human	Liver	HCC	6.63e-10	7.40e-01	0.2581
84706	GPT2	C21	Human	Oral cavity	OSCC	1.82e-03	2.55e-01	0.2678
84706	GPT2	C30	Human	Oral cavity	OSCC	4.64e-14	7.72e-01	0.3055
84706	GPT2	C43	Human	Oral cavity	OSCC	1.18e-05	1.65e-01	0.1704
84706	GPT2	C46	Human	Oral cavity	OSCC	2.52e-31	8.33e-01	0.1673
84706	GPT2	C57	Human	Oral cavity	OSCC	5.56e-06	3.34e-01	0.1679
84706	GPT2	C08	Human	Oral cavity	OSCC	5.37e-03	1.12e-01	0.1919
84706	GPT2	LN22	Human	Oral cavity	OSCC	3.54e-03	5.49e-01	0.1733
84706	GPT2	LN46	Human	Oral cavity	OSCC	1.21e-09	5.54e-01	0.1666

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease
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

∗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:00463953	Liver	NAFLD	carboxylic acid catabolic process	73/1882	236/18723	4.16e-19	1.22e-15	73
GO:00160544	Liver	NAFLD	organic acid catabolic process	73/1882	240/18723	1.20e-18	2.34e-15	73
GO:00442825	Liver	NAFLD	small molecule catabolic process	91/1882	376/18723	8.96e-16	1.31e-12	91
GO:0009063	Liver	NAFLD	cellular amino acid catabolic process	36/1882	110/18723	6.56e-11	1.99e-08	36
GO:00065203	Liver	NAFLD	cellular amino acid metabolic process	63/1882	284/18723	1.14e-09	2.17e-07	63
GO:19016053	Liver	NAFLD	alpha-amino acid metabolic process	46/1882	195/18723	2.74e-08	2.86e-06	46
GO:1901606	Liver	NAFLD	alpha-amino acid catabolic process	25/1882	87/18723	8.67e-07	4.60e-05	25
GO:00436483	Liver	NAFLD	dicarboxylic acid metabolic process	22/1882	96/18723	1.73e-04	3.08e-03	22
GO:004428211	Liver	Cirrhotic	small molecule catabolic process	151/4634	376/18723	2.20e-11	1.34e-09	151
GO:001605411	Liver	Cirrhotic	organic acid catabolic process	104/4634	240/18723	1.91e-10	9.53e-09	104
GO:004639511	Liver	Cirrhotic	carboxylic acid catabolic process	102/4634	236/18723	3.41e-10	1.63e-08	102
GO:19016051	Liver	Cirrhotic	alpha-amino acid metabolic process	82/4634	195/18723	7.72e-08	2.30e-06	82
GO:00090631	Liver	Cirrhotic	cellular amino acid catabolic process	49/4634	110/18723	4.47e-06	7.42e-05	49
GO:000652011	Liver	Cirrhotic	cellular amino acid metabolic process	103/4634	284/18723	8.88e-06	1.30e-04	103
GO:004364811	Liver	Cirrhotic	dicarboxylic acid metabolic process	43/4634	96/18723	1.42e-05	1.97e-04	43
GO:19016061	Liver	Cirrhotic	alpha-amino acid catabolic process	36/4634	87/18723	4.69e-04	3.78e-03	36
GO:004428221	Liver	HCC	small molecule catabolic process	225/7958	376/18723	6.50e-12	2.80e-10	225
GO:001605421	Liver	HCC	organic acid catabolic process	152/7958	240/18723	5.11e-11	1.92e-09	152
GO:00463952	Liver	HCC	carboxylic acid catabolic process	149/7958	236/18723	1.11e-10	3.87e-09	149
GO:19016052	Liver	HCC	alpha-amino acid metabolic process	124/7958	195/18723	2.07e-09	5.79e-08	124

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0120010	Liver	NAFLD	Carbon metabolism	26/1043	115/8465	1.39e-03	1.71e-02	1.38e-02	26
hsa0120011	Liver	NAFLD	Carbon metabolism	26/1043	115/8465	1.39e-03	1.71e-02	1.38e-02	26
hsa0120021	Liver	Cirrhotic	Carbon metabolism	64/2530	115/8465	6.37e-09	1.18e-07	7.26e-08	64
hsa012304	Liver	Cirrhotic	Biosynthesis of amino acids	35/2530	75/8465	1.54e-03	7.83e-03	4.83e-03	35
hsa0120031	Liver	Cirrhotic	Carbon metabolism	64/2530	115/8465	6.37e-09	1.18e-07	7.26e-08	64
hsa0123011	Liver	Cirrhotic	Biosynthesis of amino acids	35/2530	75/8465	1.54e-03	7.83e-03	4.83e-03	35
hsa0120041	Liver	HCC	Carbon metabolism	89/4020	115/8465	3.92e-11	6.56e-10	3.65e-10	89
hsa0123021	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa0120051	Liver	HCC	Carbon metabolism	89/4020	115/8465	3.92e-11	6.56e-10	3.65e-10	89
hsa0123031	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa0120014	Oral cavity	OSCC	Carbon metabolism	74/3704	115/8465	6.10e-06	3.05e-05	1.55e-05	74
hsa012305	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0120015	Oral cavity	OSCC	Carbon metabolism	74/3704	115/8465	6.10e-06	3.05e-05	1.55e-05	74
hsa0123012	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0120022	Oral cavity	LP	Carbon metabolism	62/2418	115/8465	8.38e-09	1.39e-07	8.99e-08	62
hsa0123022	Oral cavity	LP	Biosynthesis of amino acids	36/2418	75/8465	2.68e-04	1.51e-03	9.74e-04	36
hsa01210	Oral cavity	LP	2-Oxocarboxylic acid metabolism	11/2418	19/8465	7.01e-03	2.71e-02	1.75e-02	11
hsa0120032	Oral cavity	LP	Carbon metabolism	62/2418	115/8465	8.38e-09	1.39e-07	8.99e-08	62
hsa0123032	Oral cavity	LP	Biosynthesis of amino acids	36/2418	75/8465	2.68e-04	1.51e-03	9.74e-04	36
hsa012101	Oral cavity	LP	2-Oxocarboxylic acid metabolism	11/2418	19/8465	7.01e-03	2.71e-02	1.75e-02	11

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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

GPT2

SNV

Missense_Mutation

novel

c.200N>T

p.Pro67Leu

p.P67L

Q8TD30

protein_coding

deleterious(0)

possibly_damaging(0.872)

TCGA-A7-A3J1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrazole

GPT2

SNV

Missense_Mutation

rs367834055

c.410G>A

p.Arg137Gln

p.R137Q

Q8TD30

protein_coding

tolerated(0.19)

benign(0.145)

TCGA-B6-A0X1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GPT2

SNV

Missense_Mutation

rs745565332

c.1441N>A

p.Gly481Ser

p.G481S

Q8TD30

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A0GY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyotxan

GPT2

SNV

Missense_Mutation

novel

c.494C>G

p.Ala165Gly

p.A165G

Q8TD30

protein_coding

tolerated(0.14)

benign(0.027)

TCGA-BH-A1EO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GPT2

SNV

Missense_Mutation

c.1375C>G

p.Gln459Glu

p.Q459E

Q8TD30

protein_coding

deleterious(0.02)

benign(0)

TCGA-GM-A2DH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

GPT2

insertion

Frame_Shift_Ins

novel

c.307_308insTCGGG

p.Gln103LeufsTer12

p.Q103Lfs*12

Q8TD30

protein_coding

TCGA-AO-A0JJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophospamide

GPT2

insertion

Nonsense_Mutation

novel

c.1539_1540insGTAATGGGTGGATATGTCTTAGCCTAAATGCTGCTCCAGTTTATTGCT

p.Asp513_Phe514insValMetGlyGlyTyrValLeuAlaTerMetLeuLeuGlnPheIleAla

p.D513_F514insVMGGYVLA*MLLQFIA

Q8TD30

protein_coding

TCGA-BH-A0BA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

GPT2

SNV

Missense_Mutation

c.1259N>G

p.Thr420Arg

p.T420R

Q8TD30

protein_coding

deleterious(0.01)

probably_damaging(0.929)

TCGA-C5-A1MI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GPT2

SNV

Missense_Mutation

novel

c.901N>A

p.Val301Met

p.V301M

Q8TD30

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-ZJ-AAXJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GPT2

SNV

Missense_Mutation

rs752970046

c.397A>C

p.Lys133Gln

p.K133Q

Q8TD30

protein_coding

tolerated(0.77)

benign(0.003)

TCGA-CM-6170-01

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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