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: GMPPA

Gene summary for GMPPA

Gene summary.

Gene information	Species	Human
	Gene symbol	GMPPA
	Gene ID	29926
	Gene name	GDP-mannose pyrophosphorylase A
	Gene Alias	AAMR
	Cytomap	2q35
	Gene Type	protein-coding
	GO ID	GO:0008150
	UniProtAcc	A0A024R482

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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
29926	GMPPA	HTA11_3410_2000001011	Human	Colorectum	AD	2.65e-02	9.08e-02	0.0155
29926	GMPPA	HTA11_2487_2000001011	Human	Colorectum	SER	6.05e-13	3.97e-01	-0.1808
29926	GMPPA	HTA11_1938_2000001011	Human	Colorectum	AD	4.57e-02	1.66e-01	-0.0811
29926	GMPPA	HTA11_347_2000001011	Human	Colorectum	AD	5.81e-11	2.57e-01	-0.1954
29926	GMPPA	HTA11_411_2000001011	Human	Colorectum	SER	5.16e-05	5.27e-01	-0.2602
29926	GMPPA	HTA11_3361_2000001011	Human	Colorectum	AD	1.36e-02	2.35e-01	-0.1207
29926	GMPPA	HTA11_83_2000001011	Human	Colorectum	SER	2.85e-02	1.89e-01	-0.1526
29926	GMPPA	HTA11_696_2000001011	Human	Colorectum	AD	1.02e-13	3.01e-01	-0.1464
29926	GMPPA	HTA11_1391_2000001011	Human	Colorectum	AD	4.33e-06	2.31e-01	-0.059
29926	GMPPA	HTA11_866_3004761011	Human	Colorectum	AD	3.57e-02	1.23e-01	0.096
29926	GMPPA	HTA11_99999970781_79442	Human	Colorectum	MSS	3.92e-06	1.59e-01	0.294
29926	GMPPA	HTA11_99999971662_82457	Human	Colorectum	MSS	1.71e-10	3.25e-01	0.3859
29926	GMPPA	HTA11_99999974143_84620	Human	Colorectum	MSS	2.63e-07	2.20e-01	0.3005
29926	GMPPA	LZE7T	Human	Esophagus	ESCC	3.64e-04	1.85e-01	0.0667
29926	GMPPA	LZE8T	Human	Esophagus	ESCC	1.89e-03	1.54e-01	0.067
29926	GMPPA	LZE20T	Human	Esophagus	ESCC	1.58e-02	1.18e-01	0.0662
29926	GMPPA	LZE24T	Human	Esophagus	ESCC	1.81e-12	3.27e-01	0.0596
29926	GMPPA	P1T-E	Human	Esophagus	ESCC	8.76e-05	2.49e-01	0.0875
29926	GMPPA	P2T-E	Human	Esophagus	ESCC	5.19e-12	2.34e-01	0.1177
29926	GMPPA	P4T-E	Human	Esophagus	ESCC	7.79e-13	2.63e-01	0.1323

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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
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00051	Colorectum	AD	Fructose and mannose metabolism	17/2092	34/8465	1.25e-03	8.02e-03	5.12e-03	17
hsa000511	Colorectum	AD	Fructose and mannose metabolism	17/2092	34/8465	1.25e-03	8.02e-03	5.12e-03	17
hsa012405	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa012505	Esophagus	ESCC	Biosynthesis of nucleotide sugars	28/4205	37/8465	1.10e-03	3.42e-03	1.75e-03	28
hsa005202	Esophagus	ESCC	Amino sugar and nucleotide sugar metabolism	35/4205	49/8465	1.60e-03	4.88e-03	2.50e-03	35
hsa000512	Esophagus	ESCC	Fructose and mannose metabolism	24/4205	34/8465	1.09e-02	2.51e-02	1.29e-02	24
hsa0124012	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0125012	Esophagus	ESCC	Biosynthesis of nucleotide sugars	28/4205	37/8465	1.10e-03	3.42e-03	1.75e-03	28
hsa0052011	Esophagus	ESCC	Amino sugar and nucleotide sugar metabolism	35/4205	49/8465	1.60e-03	4.88e-03	2.50e-03	35
hsa0005111	Esophagus	ESCC	Fructose and mannose metabolism	24/4205	34/8465	1.09e-02	2.51e-02	1.29e-02	24
hsa012402	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa012403	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa00520	Oral cavity	OSCC	Amino sugar and nucleotide sugar metabolism	34/3704	49/8465	2.48e-04	8.08e-04	4.11e-04	34
hsa012404	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa012504	Oral cavity	OSCC	Biosynthesis of nucleotide sugars	25/3704	37/8465	2.93e-03	7.49e-03	3.81e-03	25
hsa005201	Oral cavity	OSCC	Amino sugar and nucleotide sugar metabolism	34/3704	49/8465	2.48e-04	8.08e-04	4.11e-04	34
hsa0124011	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa0125011	Oral cavity	OSCC	Biosynthesis of nucleotide sugars	25/3704	37/8465	2.93e-03	7.49e-03	3.81e-03	25
hsa0124021	Oral cavity	LP	Biosynthesis of cofactors	57/2418	153/8465	1.17e-02	3.91e-02	2.52e-02	57
hsa0124031	Oral cavity	LP	Biosynthesis of cofactors	57/2418	153/8465	1.17e-02	3.91e-02	2.52e-02	57

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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

GMPPA

SNV

Missense_Mutation

novel

c.101T>G

p.Val34Gly

p.V34G

Q96IJ6

protein_coding

tolerated(0.33)

possibly_damaging(0.698)

TCGA-A8-A06R-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

GMPPA

SNV

Missense_Mutation

c.296N>A

p.Arg99Gln

p.R99Q

Q96IJ6

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GMPPA

SNV

Missense_Mutation

rs147832114

c.583N>T

p.Arg195Trp

p.R195W

Q96IJ6

protein_coding

deleterious(0.01)

possibly_damaging(0.773)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GMPPA

SNV

Missense_Mutation

rs200425681

c.821C>G

p.Ala274Gly

p.A274G

Q96IJ6

protein_coding

tolerated(0.05)

possibly_damaging(0.589)

TCGA-AN-A0AT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GMPPA

SNV

Missense_Mutation

novel

c.101N>G

p.Val34Gly

p.V34G

Q96IJ6

protein_coding

tolerated(0.33)

possibly_damaging(0.698)

TCGA-AQ-A1H3-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

GMPPA

SNV

Missense_Mutation

novel

c.101N>G

p.Val34Gly

p.V34G

Q96IJ6

protein_coding

tolerated(0.33)

possibly_damaging(0.698)

TCGA-BH-A0HO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

GMPPA

SNV

Missense_Mutation

rs200425681

c.821C>G

p.Ala274Gly

p.A274G

Q96IJ6

protein_coding

tolerated(0.05)

possibly_damaging(0.589)

TCGA-C8-A273-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

GMPPA

SNV

Missense_Mutation

novel

c.101T>G

p.Val34Gly

p.V34G

Q96IJ6

protein_coding

tolerated(0.33)

possibly_damaging(0.698)

TCGA-EW-A1J3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

GMPPA

SNV

Missense_Mutation

novel

c.101T>G

p.Val34Gly

p.V34G

Q96IJ6

protein_coding

tolerated(0.33)

possibly_damaging(0.698)

TCGA-EW-A1PH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

GMPPA

insertion

Frame_Shift_Ins

novel

c.562_563insACAGGCTTTCGTCATA

p.Pro188HisfsTer7

p.P188Hfs*7

Q96IJ6

protein_coding

TCGA-A8-A07G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-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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