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: TPI1

Gene summary for TPI1

Gene summary.

Gene information	Species	Human
	Gene symbol	TPI1
	Gene ID	7167
	Gene name	triosephosphate isomerase 1
	Gene Alias	HEL-S-49
	Cytomap	12p13.31
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	P60174

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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
7167	TPI1	GSM4909281	Human	Breast	IDC	1.14e-09	3.64e-01	0.21
7167	TPI1	GSM4909282	Human	Breast	IDC	1.56e-65	6.89e-01	-0.0288
7167	TPI1	GSM4909285	Human	Breast	IDC	2.47e-12	4.17e-01	0.21
7167	TPI1	GSM4909286	Human	Breast	IDC	2.51e-08	-2.59e-02	0.1081
7167	TPI1	GSM4909287	Human	Breast	IDC	6.10e-06	2.48e-01	0.2057
7167	TPI1	GSM4909288	Human	Breast	IDC	4.34e-05	2.10e-01	0.0988
7167	TPI1	GSM4909294	Human	Breast	IDC	2.76e-05	-1.10e-01	0.2022
7167	TPI1	GSM4909296	Human	Breast	IDC	4.05e-16	2.16e-01	0.1524
7167	TPI1	GSM4909297	Human	Breast	IDC	4.18e-21	-7.39e-02	0.1517
7167	TPI1	GSM4909298	Human	Breast	IDC	2.12e-11	-3.27e-01	0.1551
7167	TPI1	GSM4909299	Human	Breast	IDC	2.92e-03	-2.52e-01	0.035
7167	TPI1	GSM4909301	Human	Breast	IDC	2.99e-02	-2.44e-01	0.1577
7167	TPI1	GSM4909311	Human	Breast	IDC	1.21e-47	-4.15e-01	0.1534
7167	TPI1	GSM4909312	Human	Breast	IDC	3.12e-12	-2.04e-01	0.1552
7167	TPI1	GSM4909315	Human	Breast	IDC	5.36e-14	3.30e-01	0.21
7167	TPI1	GSM4909316	Human	Breast	IDC	7.18e-05	1.56e-01	0.21
7167	TPI1	GSM4909319	Human	Breast	IDC	2.54e-68	-8.46e-02	0.1563
7167	TPI1	GSM4909320	Human	Breast	IDC	2.32e-04	-2.76e-01	0.1575
7167	TPI1	GSM4909321	Human	Breast	IDC	2.40e-20	1.13e-01	0.1559
7167	TPI1	ctrl6	Human	Breast	Precancer	9.06e-32	6.96e-01	-0.0061

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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
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
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
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:00060066	Breast	Precancer	glucose metabolic process	23/1080	196/18723	9.54e-04	1.07e-02	23
GO:00059966	Breast	Precancer	monosaccharide metabolic process	27/1080	257/18723	1.94e-03	1.88e-02	27
GO:00193186	Breast	Precancer	hexose metabolic process	25/1080	237/18723	2.64e-03	2.36e-02	25
GO:004603414	Breast	IDC	ATP metabolic process	85/1434	277/18723	6.42e-30	1.82e-26	85
GO:000609113	Breast	IDC	generation of precursor metabolites and energy	103/1434	490/18723	1.53e-21	1.74e-18	103
GO:000915014	Breast	IDC	purine ribonucleotide metabolic process	55/1434	368/18723	1.30e-06	5.72e-05	55
GO:001969314	Breast	IDC	ribose phosphate metabolic process	58/1434	396/18723	1.31e-06	5.73e-05	58
GO:000675313	Breast	IDC	nucleoside phosphate metabolic process	68/1434	497/18723	2.01e-06	8.23e-05	68
GO:000911713	Breast	IDC	nucleotide metabolic process	67/1434	489/18723	2.28e-06	9.05e-05	67
GO:000925914	Breast	IDC	ribonucleotide metabolic process	56/1434	385/18723	2.47e-06	9.63e-05	56
GO:000616314	Breast	IDC	purine nucleotide metabolic process	56/1434	396/18723	5.90e-06	1.90e-04	56
GO:004693913	Breast	IDC	nucleotide phosphorylation	22/1434	101/18723	6.31e-06	1.98e-04	22
GO:007252114	Breast	IDC	purine-containing compound metabolic process	57/1434	416/18723	1.28e-05	3.31e-04	57
GO:000616513	Breast	IDC	nucleoside diphosphate phosphorylation	21/1434	99/18723	1.57e-05	3.94e-04	21
GO:000913213	Breast	IDC	nucleoside diphosphate metabolic process	23/1434	124/18723	6.08e-05	1.27e-03	23
GO:000609613	Breast	IDC	glycolytic process	17/1434	81/18723	1.13e-04	2.11e-03	17
GO:000675713	Breast	IDC	ATP generation from ADP	17/1434	82/18723	1.33e-04	2.40e-03	17
GO:000918513	Breast	IDC	ribonucleoside diphosphate metabolic process	20/1434	106/18723	1.41e-04	2.49e-03	20
GO:000609013	Breast	IDC	pyruvate metabolic process	19/1434	106/18723	4.05e-04	5.60e-03	19
GO:004603113	Breast	IDC	ADP metabolic process	17/1434	90/18723	4.27e-04	5.84e-03	17

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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
hsa0120012	Breast	Precancer	Carbon metabolism	18/684	115/8465	4.79e-03	2.75e-02	2.11e-02	18
hsa0001013	Breast	Precancer	Glycolysis / Gluconeogenesis	13/684	67/8465	2.39e-03	1.51e-02	1.16e-02	13
hsa0120013	Breast	Precancer	Carbon metabolism	18/684	115/8465	4.79e-03	2.75e-02	2.11e-02	18
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
hsa00051	Colorectum	AD	Fructose and mannose metabolism	17/2092	34/8465	1.25e-03	8.02e-03	5.12e-03	17
hsa01230	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
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
hsa000511	Colorectum	AD	Fructose and mannose metabolism	17/2092	34/8465	1.25e-03	8.02e-03	5.12e-03	17
hsa012301	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
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
hsa012302	Colorectum	SER	Biosynthesis of amino acids	23/1580	75/8465	8.11e-03	4.14e-02	3.01e-02	23
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
hsa012303	Colorectum	SER	Biosynthesis of amino acids	23/1580	75/8465	8.11e-03	4.14e-02	3.01e-02	23
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

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
TPI1	PVA	Liver	Cirrhotic	MYL6,PFN1,ACTB, etc.	4.13e-01

∗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

TPI1

SNV

Missense_Mutation

novel

c.856C>A

p.Gln286Lys

p.Q286K

P60174

protein_coding

tolerated_low_confidence(0.25)

benign(0)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TPI1

SNV

Missense_Mutation

c.394N>A

p.Gly132Arg

p.G132R

P60174

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0FT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TPI1

insertion

Nonsense_Mutation

novel

c.838_839insGTCTTACTTAGGCCAGCTTCTTGTTCTAGGCCCAGGAAGT

p.Asp280GlyfsTer4

p.D280Gfs*4

P60174

protein_coding

TCGA-A8-A09C-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TPI1

SNV

Missense_Mutation

novel

c.479N>A

p.Gly160Glu

p.G160E

P60174

protein_coding

tolerated(0.05)

benign(0.069)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

TPI1

insertion

Nonsense_Mutation

novel

c.777_778insTAAGT

p.Ser260Ter

p.S260*

P60174

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

TPI1

insertion

Nonsense_Mutation

novel

c.777_778insTAAGTA

p.Ala259_Ser260insTer

p.A259_S260ins*

P60174

protein_coding

TCGA-DS-A1OD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TPI1

SNV

Missense_Mutation

c.823N>G

p.Lys275Glu

p.K275E

P60174

protein_coding

deleterious(0.01)

benign(0.146)

TCGA-AA-3715-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TPI1

SNV

Missense_Mutation

c.519N>C

p.Glu173Asp

p.E173D

P60174

protein_coding

deleterious(0.01)

benign(0.399)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TPI1

SNV

Missense_Mutation

rs782032967

c.108C>G

p.Ser36Arg

p.S36R

P60174

protein_coding

tolerated_low_confidence(0.13)

benign(0.024)

TCGA-CM-6674-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

TPI1

SNV

Missense_Mutation

c.143N>A

p.Gly48Glu

p.G48E

P60174

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-G4-6304-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

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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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