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: GPI

Gene summary for GPI

Gene summary.

Gene information	Species	Human
	Gene symbol	GPI
	Gene ID	2821
	Gene name	glucose-6-phosphate isomerase
	Gene Alias	AMF
	Cytomap	19q13.11
	Gene Type	protein-coding
	GO ID	GO:0001667
	UniProtAcc	P06744

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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
2821	GPI	GSM4909281	Human	Breast	IDC	4.43e-03	1.65e-01	0.21
2821	GPI	GSM4909282	Human	Breast	IDC	6.49e-19	4.27e-01	-0.0288
2821	GPI	GSM4909285	Human	Breast	IDC	6.93e-28	4.93e-01	0.21
2821	GPI	GSM4909287	Human	Breast	IDC	6.68e-05	2.48e-01	0.2057
2821	GPI	GSM4909290	Human	Breast	IDC	4.40e-02	1.98e-01	0.2096
2821	GPI	GSM4909291	Human	Breast	IDC	5.14e-07	3.68e-01	0.1753
2821	GPI	GSM4909292	Human	Breast	IDC	1.61e-04	5.87e-01	0.1236
2821	GPI	GSM4909293	Human	Breast	IDC	1.73e-07	2.06e-01	0.1581
2821	GPI	GSM4909304	Human	Breast	IDC	3.23e-07	2.34e-01	0.1636
2821	GPI	GSM4909311	Human	Breast	IDC	7.05e-04	-5.55e-02	0.1534
2821	GPI	GSM4909315	Human	Breast	IDC	1.19e-22	6.25e-01	0.21
2821	GPI	GSM4909317	Human	Breast	IDC	4.20e-11	3.57e-01	0.1355
2821	GPI	GSM4909319	Human	Breast	IDC	2.59e-04	-9.27e-02	0.1563
2821	GPI	brca2	Human	Breast	Precancer	1.27e-03	5.66e-02	-0.024
2821	GPI	brca3	Human	Breast	Precancer	4.46e-09	2.21e-01	-0.0263
2821	GPI	NCCBC5	Human	Breast	DCIS	1.47e-17	6.05e-01	0.2046
2821	GPI	P1	Human	Breast	IDC	9.28e-04	-4.42e-02	0.1527
2821	GPI	P2	Human	Breast	IDC	3.71e-11	5.39e-01	0.21
2821	GPI	DCIS2	Human	Breast	DCIS	8.36e-41	1.25e-01	0.0085
2821	GPI	HTA11_3410_2000001011	Human	Colorectum	AD	3.54e-09	3.86e-01	0.0155

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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
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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67
GO:20001169	Breast	Precancer	regulation of cysteine-type endopeptidase activity	43/1080	235/18723	1.30e-11	1.83e-09	43
GO:00432819	Breast	Precancer	regulation of cysteine-type endopeptidase activity involved in apoptotic process	40/1080	209/18723	1.59e-11	2.07e-09	40
GO:00485459	Breast	Precancer	response to steroid hormone	53/1080	339/18723	3.07e-11	3.66e-09	53
GO:00458619	Breast	Precancer	negative regulation of proteolysis	50/1080	351/18723	2.99e-09	2.39e-07	50
GO:00709979	Breast	Precancer	neuron death	50/1080	361/18723	7.75e-09	5.70e-07	50
GO:00514029	Breast	Precancer	neuron apoptotic process	38/1080	246/18723	2.68e-08	1.75e-06	38
GO:00513468	Breast	Precancer	negative regulation of hydrolase activity	50/1080	379/18723	3.85e-08	2.34e-06	50
GO:00104668	Breast	Precancer	negative regulation of peptidase activity	38/1080	262/18723	1.46e-07	7.82e-06	38
GO:00109519	Breast	Precancer	negative regulation of endopeptidase activity	37/1080	252/18723	1.55e-07	8.05e-06	37
GO:00022629	Breast	Precancer	myeloid cell homeostasis	27/1080	157/18723	3.10e-07	1.49e-05	27
GO:20001179	Breast	Precancer	negative regulation of cysteine-type endopeptidase activity	19/1080	86/18723	3.36e-07	1.58e-05	19
GO:00196938	Breast	Precancer	ribose phosphate metabolic process	49/1080	396/18723	3.81e-07	1.78e-05	49
GO:00100389	Breast	Precancer	response to metal ion	47/1080	373/18723	3.88e-07	1.79e-05	47
GO:00091509	Breast	Precancer	purine ribonucleotide metabolic process	46/1080	368/18723	6.47e-07	2.71e-05	46
GO:00091179	Breast	Precancer	nucleotide metabolic process	56/1080	489/18723	7.40e-07	3.00e-05	56
GO:00092598	Breast	Precancer	ribonucleotide metabolic process	47/1080	385/18723	9.69e-07	3.84e-05	47

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0001010	Breast	Precancer	Glycolysis / Gluconeogenesis	13/684	67/8465	2.39e-03	1.51e-02	1.16e-02	13
hsa0001013	Breast	Precancer	Glycolysis / Gluconeogenesis	13/684	67/8465	2.39e-03	1.51e-02	1.16e-02	13
hsa01200	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa00010	Colorectum	AD	Glycolysis / Gluconeogenesis	34/2092	67/8465	3.63e-06	4.34e-05	2.77e-05	34
hsa012001	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa000101	Colorectum	AD	Glycolysis / Gluconeogenesis	34/2092	67/8465	3.63e-06	4.34e-05	2.77e-05	34
hsa012002	Colorectum	SER	Carbon metabolism	40/1580	115/8465	2.77e-05	3.41e-04	2.47e-04	40
hsa000102	Colorectum	SER	Glycolysis / Gluconeogenesis	24/1580	67/8465	6.62e-04	5.36e-03	3.89e-03	24
hsa012003	Colorectum	SER	Carbon metabolism	40/1580	115/8465	2.77e-05	3.41e-04	2.47e-04	40
hsa000103	Colorectum	SER	Glycolysis / Gluconeogenesis	24/1580	67/8465	6.62e-04	5.36e-03	3.89e-03	24
hsa012004	Colorectum	MSS	Carbon metabolism	43/1875	115/8465	1.37e-04	1.17e-03	7.19e-04	43
hsa000104	Colorectum	MSS	Glycolysis / Gluconeogenesis	28/1875	67/8465	2.36e-04	1.81e-03	1.11e-03	28
hsa012005	Colorectum	MSS	Carbon metabolism	43/1875	115/8465	1.37e-04	1.17e-03	7.19e-04	43
hsa000105	Colorectum	MSS	Glycolysis / Gluconeogenesis	28/1875	67/8465	2.36e-04	1.81e-03	1.11e-03	28
hsa012006	Colorectum	FAP	Carbon metabolism	38/1404	115/8465	1.04e-05	1.44e-04	8.76e-05	38
hsa000106	Colorectum	FAP	Glycolysis / Gluconeogenesis	24/1404	67/8465	1.05e-04	9.46e-04	5.76e-04	24
hsa01250	Colorectum	FAP	Biosynthesis of nucleotide sugars	13/1404	37/8465	4.79e-03	1.91e-02	1.16e-02	13
hsa012007	Colorectum	FAP	Carbon metabolism	38/1404	115/8465	1.04e-05	1.44e-04	8.76e-05	38
hsa000107	Colorectum	FAP	Glycolysis / Gluconeogenesis	24/1404	67/8465	1.05e-04	9.46e-04	5.76e-04	24
hsa012501	Colorectum	FAP	Biosynthesis of nucleotide sugars	13/1404	37/8465	4.79e-03	1.91e-02	1.16e-02	13

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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

GPI

SNV

Missense_Mutation

novel

c.1173N>T

p.Trp391Cys

p.W391C

P06744

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.992)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GPI

SNV

Missense_Mutation

novel

c.781N>G

p.Thr261Ala

p.T261A

P06744

protein_coding

tolerated_low_confidence(1)

benign(0.009)

TCGA-BH-A0B3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

GPI

SNV

Missense_Mutation

c.1320N>G

p.Phe440Leu

p.F440L

P06744

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.999)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GPI

insertion

In_Frame_Ins

novel

c.1640_1641insTTTAAGTTCTGAGATACGTGTGGAGAATGTGCAGGTTTGTTA

p.Thr547_Ser548insLeuSerSerGluIleArgValGluAsnValGlnValCysTyr

p.T547_S548insLSSEIRVENVQVCY

P06744

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

GPI

insertion

Nonsense_Mutation

novel

c.847_848insCCTGGGTGTGTCCGTGTCTGAGGAGGTGGGCCCTGGCACAGGTAT

p.Gly283delinsAlaTrpValCysProCysLeuArgArgTrpAlaLeuAlaGlnValTer

p.G283delinsAWVCPCLRRWALAQV*

P06744

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GPI

SNV

Missense_Mutation

rs199570323

c.1388N>T

p.Ala463Val

p.A463V

P06744

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.453)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GPI

SNV

Missense_Mutation

c.355G>T

p.Ala119Ser

p.A119S

P06744

protein_coding

tolerated_low_confidence(0.12)

benign(0.162)

TCGA-HM-A3JK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GPI

SNV

Missense_Mutation

rs748408705

c.850C>T

p.Arg284Cys

p.R284C

P06744

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-AA-A022-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

GPI

SNV

Missense_Mutation

c.364N>T

p.Arg122Trp

p.R122W

P06744

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.806)

TCGA-CM-6162-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

oxaliplatin

GPI

SNV

Missense_Mutation

rs370578920

c.374N>G

p.Asn125Ser

p.N125S

P06744

protein_coding

tolerated_low_confidence(1)

benign(0.003)

TCGA-AG-3887-01

Colorectum

rectum adenocarcinoma

Male

>=65

I/II

Chemotherapy

irinotecan

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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
2821	GPI	ENZYME, GROWTH FACTOR, DRUGGABLE GENOME		6-AN		10884030
2821	GPI	ENZYME, GROWTH FACTOR, DRUGGABLE GENOME		FDG	FLUDEOXYGLUCOSE-F18	10963181
2821	GPI	ENZYME, GROWTH FACTOR, DRUGGABLE GENOME		HEREGULIN		10667603

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