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: GMDS

Gene summary for GMDS

Gene summary.

Gene information	Species	Human
	Gene symbol	GMDS
	Gene ID	2762
	Gene name	GDP-mannose 4,6-dehydratase
	Gene Alias	GMD
	Cytomap	6p25.3
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	O60547

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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
2762	GMDS	CCI_1	Human	Cervix	CC	2.28e-27	2.08e+00	0.528
2762	GMDS	CCI_2	Human	Cervix	CC	1.45e-13	1.30e+00	0.5249
2762	GMDS	CCI_3	Human	Cervix	CC	8.56e-23	1.60e+00	0.516
2762	GMDS	HTA11_2487_2000001011	Human	Colorectum	SER	1.40e-10	8.12e-01	-0.1808
2762	GMDS	HTA11_2951_2000001011	Human	Colorectum	AD	1.36e-02	3.82e-01	0.0216
2762	GMDS	HTA11_1938_2000001011	Human	Colorectum	AD	2.18e-29	1.57e+00	-0.0811
2762	GMDS	HTA11_78_2000001011	Human	Colorectum	AD	2.84e-31	1.73e+00	-0.1088
2762	GMDS	HTA11_347_2000001011	Human	Colorectum	AD	2.48e-16	9.31e-01	-0.1954
2762	GMDS	HTA11_411_2000001011	Human	Colorectum	SER	1.53e-08	1.03e+00	-0.2602
2762	GMDS	HTA11_2112_2000001011	Human	Colorectum	SER	2.20e-16	5.60e-01	-0.2196
2762	GMDS	HTA11_3361_2000001011	Human	Colorectum	AD	4.23e-04	4.44e-01	-0.1207
2762	GMDS	HTA11_83_2000001011	Human	Colorectum	SER	2.30e-30	1.36e+00	-0.1526
2762	GMDS	HTA11_696_2000001011	Human	Colorectum	AD	1.34e-17	1.13e+00	-0.1464
2762	GMDS	HTA11_866_2000001011	Human	Colorectum	AD	8.25e-13	9.87e-01	-0.1001
2762	GMDS	HTA11_1391_2000001011	Human	Colorectum	AD	1.57e-24	1.86e+00	-0.059
2762	GMDS	HTA11_546_2000001011	Human	Colorectum	AD	1.43e-14	1.10e+00	-0.0842
2762	GMDS	HTA11_9341_2000001011	Human	Colorectum	SER	6.45e-05	4.45e-01	-0.00410000000000005
2762	GMDS	HTA11_4255_2000001011	Human	Colorectum	SER	1.72e-20	8.35e-01	0.0446
2762	GMDS	HTA11_8622_2000001021	Human	Colorectum	SER	2.27e-06	5.29e-01	0.0528
2762	GMDS	HTA11_7663_2000001011	Human	Colorectum	SER	2.57e-46	1.61e+00	0.0131

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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

∗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:00072194	Cervix	CC	Notch signaling pathway	39/2311	172/18723	1.08e-04	1.38e-03	39
GO:0009225	Colorectum	AD	nucleotide-sugar metabolic process	16/3918	36/18723	1.27e-03	1.12e-02	16
GO:0007219	Colorectum	AD	Notch signaling pathway	50/3918	172/18723	6.92e-03	4.26e-02	50
GO:00092251	Colorectum	SER	nucleotide-sugar metabolic process	12/2897	36/18723	6.11e-03	4.42e-02	12
GO:00092252	Colorectum	MSS	nucleotide-sugar metabolic process	14/3467	36/18723	3.40e-03	2.56e-02	14
GO:00072191	Colorectum	FAP	Notch signaling pathway	38/2622	172/18723	2.56e-03	2.01e-02	38
GO:00072192	Colorectum	CRC	Notch signaling pathway	36/2078	172/18723	1.26e-04	2.42e-03	36
GO:00092253	Colorectum	CRC	nucleotide-sugar metabolic process	10/2078	36/18723	4.68e-03	3.62e-02	10
GO:00072197	Esophagus	ESCC	Notch signaling pathway	106/8552	172/18723	1.74e-05	1.55e-04	106
GO:00092256	Esophagus	ESCC	nucleotide-sugar metabolic process	29/8552	36/18723	1.91e-05	1.67e-04	29
GO:00092262	Esophagus	ESCC	nucleotide-sugar biosynthetic process	14/8552	19/18723	1.27e-02	4.21e-02	14
GO:00092254	Liver	HCC	nucleotide-sugar metabolic process	25/7958	36/18723	9.87e-04	5.71e-03	25
GO:00072193	Lung	AIS	Notch signaling pathway	29/1849	172/18723	2.93e-03	2.92e-02	29
GO:00092255	Oral cavity	OSCC	nucleotide-sugar metabolic process	26/7305	36/18723	5.44e-05	4.51e-04	26
GO:00072196	Oral cavity	OSCC	Notch signaling pathway	92/7305	172/18723	7.84e-05	6.08e-04	92
GO:00092261	Oral cavity	OSCC	nucleotide-sugar biosynthetic process	14/7305	19/18723	2.31e-03	1.02e-02	14
GO:000721921	Oral cavity	NEOLP	Notch signaling pathway	32/2005	172/18723	1.31e-03	9.48e-03	32
GO:00072195	Prostate	BPH	Notch signaling pathway	41/3107	172/18723	8.95e-03	3.83e-02	41
GO:000721912	Prostate	Tumor	Notch signaling pathway	44/3246	172/18723	4.02e-03	2.04e-02	44
GO:0009226	Prostate	Tumor	nucleotide-sugar biosynthetic process	8/3246	19/18723	1.00e-02	4.20e-02	8

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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
hsa01250	Colorectum	FAP	Biosynthesis of nucleotide sugars	13/1404	37/8465	4.79e-03	1.91e-02	1.16e-02	13
hsa012501	Colorectum	FAP	Biosynthesis of nucleotide sugars	13/1404	37/8465	4.79e-03	1.91e-02	1.16e-02	13
hsa012502	Colorectum	CRC	Biosynthesis of nucleotide sugars	12/1091	37/8465	1.66e-03	1.20e-02	8.16e-03	12
hsa012503	Colorectum	CRC	Biosynthesis of nucleotide sugars	12/1091	37/8465	1.66e-03	1.20e-02	8.16e-03	12
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
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
hsa00520	Oral cavity	OSCC	Amino sugar and nucleotide sugar metabolism	34/3704	49/8465	2.48e-04	8.08e-04	4.11e-04	34
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
hsa0125011	Oral cavity	OSCC	Biosynthesis of nucleotide sugars	25/3704	37/8465	2.93e-03	7.49e-03	3.81e-03	25

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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

GMDS

SNV

Missense_Mutation

c.107G>C

p.Gly36Ala

p.G36A

O60547

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-AN-A0XV-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

GMDS

SNV

Missense_Mutation

c.121N>C

p.Glu41Gln

p.E41Q

O60547

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.992)

TCGA-B6-A0RV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

GMDS

SNV

Missense_Mutation

c.655G>C

p.Val219Leu

p.V219L

O60547

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-D8-A142-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamid

GMDS

deletion

Frame_Shift_Del

c.166_194delNNNNNNNNNNNNNNNNNNNNNNNNNNNNN

p.Arg56Ter

p.R56*

O60547

protein_coding

TCGA-AN-A0AL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

GMDS

insertion

Nonsense_Mutation

novel

c.494_495insTCAATCAATTCGATTGTCAAATAATGCACTGTTGGCATTACAAAAGTA

p.Ile165_Pro166insGlnSerIleArgLeuSerAsnAsnAlaLeuLeuAlaLeuGlnLysTer

p.I165_P166insQSIRLSNNALLALQK*

O60547

protein_coding

TCGA-AN-A0FW-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

GMDS

SNV

Missense_Mutation

c.1098G>C

p.Met366Ile

p.M366I

O60547

protein_coding

tolerated_low_confidence(0.14)

benign(0.034)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

GMDS

SNV

Missense_Mutation

rs759353627

c.191N>A

p.Arg64Gln

p.R64Q

O60547

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

GMDS

SNV

Missense_Mutation

rs771650335

c.166N>T

p.Arg56Trp

p.R56W

O60547

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-CM-6162-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

oxaliplatin

GMDS

SNV

Missense_Mutation

rs748622436

c.401G>A

p.Arg134Gln

p.R134Q

O60547

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.949)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

GMDS

insertion

Nonsense_Mutation

novel

c.401_402insTTGACGGAGTTGGCACTCTACG

p.Leu135Ter

p.L135*

O60547

protein_coding

TCGA-F4-6570-01

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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