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: OGDH

Gene summary for OGDH

Gene summary.

Gene information	Species	Human
	Gene symbol	OGDH
	Gene ID	4967
	Gene name	oxoglutarate dehydrogenase
	Gene Alias	AKGDH
	Cytomap	7p13
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	A0A140VJQ5

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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
4967	OGDH	CCI_1	Human	Cervix	CC	1.32e-02	8.91e-01	0.528
4967	OGDH	CCI_3	Human	Cervix	CC	5.28e-07	6.63e-01	0.516
4967	OGDH	HTA11_2487_2000001011	Human	Colorectum	SER	1.02e-04	5.94e-01	-0.1808
4967	OGDH	HTA11_347_2000001011	Human	Colorectum	AD	1.77e-12	5.87e-01	-0.1954
4967	OGDH	HTA11_411_2000001011	Human	Colorectum	SER	4.18e-03	9.58e-01	-0.2602
4967	OGDH	HTA11_2112_2000001011	Human	Colorectum	SER	1.82e-04	7.84e-01	-0.2196
4967	OGDH	HTA11_696_2000001011	Human	Colorectum	AD	2.60e-06	5.18e-01	-0.1464
4967	OGDH	A002-C-010	Human	Colorectum	FAP	6.14e-03	-2.23e-01	0.242
4967	OGDH	A001-C-207	Human	Colorectum	FAP	1.10e-04	-3.52e-01	0.1278
4967	OGDH	A015-C-203	Human	Colorectum	FAP	9.74e-27	-4.33e-01	-0.1294
4967	OGDH	A015-C-204	Human	Colorectum	FAP	6.65e-05	-2.95e-01	-0.0228
4967	OGDH	A014-C-040	Human	Colorectum	FAP	3.78e-06	-5.40e-01	-0.1184
4967	OGDH	A002-C-201	Human	Colorectum	FAP	2.61e-11	-3.31e-01	0.0324
4967	OGDH	A002-C-203	Human	Colorectum	FAP	6.95e-04	-8.85e-02	0.2786
4967	OGDH	A001-C-119	Human	Colorectum	FAP	1.67e-08	-4.18e-01	-0.1557
4967	OGDH	A001-C-108	Human	Colorectum	FAP	1.45e-20	-4.24e-01	-0.0272
4967	OGDH	A002-C-205	Human	Colorectum	FAP	8.48e-22	-3.66e-01	-0.1236
4967	OGDH	A001-C-104	Human	Colorectum	FAP	2.17e-05	-2.89e-01	0.0184
4967	OGDH	A015-C-005	Human	Colorectum	FAP	1.31e-04	-2.80e-01	-0.0336
4967	OGDH	A015-C-006	Human	Colorectum	FAP	1.12e-14	-4.66e-01	-0.0994

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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
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:004603410	Cervix	CC	ATP metabolic process	90/2311	277/18723	7.90e-19	2.36e-15	90
GO:00090609	Cervix	CC	aerobic respiration	60/2311	189/18723	1.59e-12	6.36e-10	60
GO:00453339	Cervix	CC	cellular respiration	66/2311	230/18723	2.07e-11	5.39e-09	66
GO:00060919	Cervix	CC	generation of precursor metabolites and energy	105/2311	490/18723	7.40e-09	6.61e-07	105
GO:00159809	Cervix	CC	energy derivation by oxidation of organic compounds	74/2311	318/18723	3.83e-08	2.53e-06	74
GO:00196939	Cervix	CC	ribose phosphate metabolic process	72/2311	396/18723	4.49e-04	4.48e-03	72
GO:00092599	Cervix	CC	ribonucleotide metabolic process	70/2311	385/18723	5.35e-04	5.18e-03	70
GO:000915010	Cervix	CC	purine ribonucleotide metabolic process	66/2311	368/18723	1.09e-03	9.07e-03	66
GO:00219541	Cervix	CC	central nervous system neuron development	19/2311	81/18723	3.96e-03	2.48e-02	19
GO:000616310	Cervix	CC	purine nucleotide metabolic process	67/2311	396/18723	4.41e-03	2.69e-02	67
GO:00309003	Cervix	CC	forebrain development	64/2311	379/18723	5.53e-03	3.19e-02	64
GO:007252110	Cervix	CC	purine-containing compound metabolic process	69/2311	416/18723	6.27e-03	3.54e-02	69
GO:00067346	Cervix	CC	NADH metabolic process	9/2311	29/18723	6.49e-03	3.61e-02	9
GO:000913510	Cervix	CC	purine nucleoside diphosphate metabolic process	22/2311	103/18723	6.75e-03	3.71e-02	22
GO:000917910	Cervix	CC	purine ribonucleoside diphosphate metabolic process	22/2311	103/18723	6.75e-03	3.71e-02	22
GO:000911710	Cervix	CC	nucleotide metabolic process	79/2311	489/18723	7.16e-03	3.85e-02	79
GO:00215433	Cervix	CC	pallium development	32/2311	169/18723	8.73e-03	4.48e-02	32
GO:00060969	Cervix	CC	glycolytic process	18/2311	81/18723	8.92e-03	4.54e-02	18
GO:00091859	Cervix	CC	ribonucleoside diphosphate metabolic process	22/2311	106/18723	9.52e-03	4.72e-02	22
GO:00067579	Cervix	CC	ATP generation from ADP	18/2311	82/18723	1.01e-02	4.94e-02	18

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa01200	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa00020	Colorectum	AD	Citrate cycle (TCA cycle)	20/2092	30/8465	1.43e-06	1.77e-05	1.13e-05	20
hsa012001	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa000201	Colorectum	AD	Citrate cycle (TCA cycle)	20/2092	30/8465	1.43e-06	1.77e-05	1.13e-05	20
hsa000202	Colorectum	SER	Citrate cycle (TCA cycle)	16/1580	30/8465	2.06e-05	2.74e-04	1.99e-04	16
hsa012002	Colorectum	SER	Carbon metabolism	40/1580	115/8465	2.77e-05	3.41e-04	2.47e-04	40
hsa000203	Colorectum	SER	Citrate cycle (TCA cycle)	16/1580	30/8465	2.06e-05	2.74e-04	1.99e-04	16
hsa012003	Colorectum	SER	Carbon metabolism	40/1580	115/8465	2.77e-05	3.41e-04	2.47e-04	40
hsa012006	Colorectum	FAP	Carbon metabolism	38/1404	115/8465	1.04e-05	1.44e-04	8.76e-05	38
hsa000206	Colorectum	FAP	Citrate cycle (TCA cycle)	14/1404	30/8465	1.16e-04	1.02e-03	6.21e-04	14
hsa012007	Colorectum	FAP	Carbon metabolism	38/1404	115/8465	1.04e-05	1.44e-04	8.76e-05	38
hsa000207	Colorectum	FAP	Citrate cycle (TCA cycle)	14/1404	30/8465	1.16e-04	1.02e-03	6.21e-04	14
hsa012008	Colorectum	CRC	Carbon metabolism	28/1091	115/8465	5.43e-04	5.48e-03	3.72e-03	28
hsa000208	Colorectum	CRC	Citrate cycle (TCA cycle)	11/1091	30/8465	8.16e-04	6.99e-03	4.74e-03	11
hsa012009	Colorectum	CRC	Carbon metabolism	28/1091	115/8465	5.43e-04	5.48e-03	3.72e-03	28
hsa000209	Colorectum	CRC	Citrate cycle (TCA cycle)	11/1091	30/8465	8.16e-04	6.99e-03	4.74e-03	11
hsa0002014	Esophagus	ESCC	Citrate cycle (TCA cycle)	27/4205	30/8465	3.48e-06	1.94e-05	9.95e-06	27
hsa0120023	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0002015	Esophagus	ESCC	Citrate cycle (TCA cycle)	27/4205	30/8465	3.48e-06	1.94e-05	9.95e-06	27
hsa0120033	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79

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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

OGDH

SNV

Missense_Mutation

novel

c.842N>C

p.Glu281Ala

p.E281A

Q02218

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-5L-AAT0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

OGDH

SNV

Missense_Mutation

novel

c.122N>G

p.Ser41Cys

p.S41C

Q02218

protein_coding

deleterious(0.04)

benign(0.345)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

OGDH

SNV

Missense_Mutation

c.1560N>A

p.Met520Ile

p.M520I

Q02218

protein_coding

tolerated(0.15)

probably_damaging(0.953)

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

OGDH

SNV

Missense_Mutation

novel

c.2602G>T

p.Ala868Ser

p.A868S

Q02218

protein_coding

deleterious(0)

possibly_damaging(0.834)

TCGA-A2-A0T2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

OGDH

SNV

Missense_Mutation

c.2023N>A

p.Gly675Ser

p.G675S

Q02218

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A5QM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

OGDH

SNV

Missense_Mutation

c.2307N>T

p.Trp769Cys

p.W769C

Q02218

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

OGDH

SNV

Missense_Mutation

c.1120N>T

p.Pro374Ser

p.P374S

Q02218

protein_coding

deleterious(0)

probably_damaging(0.967)

TCGA-BH-A1ES-06

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

OGDH

SNV

Missense_Mutation

novel

c.2602N>T

p.Ala868Ser

p.A868S

Q02218

protein_coding

deleterious(0)

possibly_damaging(0.834)

TCGA-C8-A26X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

OGDH

SNV

Missense_Mutation

c.1692N>C

p.Lys564Asn

p.K564N

Q02218

protein_coding

tolerated(0.27)

benign(0.05)

TCGA-D8-A1X9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin+cyclophosphamide

OGDH

SNV

Missense_Mutation

novel

c.1959N>T

p.Trp653Cys

p.W653C

Q02218

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-E2-A576-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

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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
4967	OGDH	NA		CPI-613
4967	OGDH	NA		valproic acid		23407051

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