Cancer Cell Metabolism Database ~~ Bioinformatics and Systems Medicine Laboratory ~~

Cancer Cell Metabolism Gene Database

Cancer Cell Metabolism Gene DB

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	Gene Summary
	Phenotypic Information (metabolism pathway, cancer, disease, phenome)
	Mutations : SVs, CNVs, SNVs
	Gene expression: GE, Protein, DEGE, CNV vs GE
	Gene-Gene Network Information: Co-Expression Network, Interacting Genes & KEGG
	Pharmacological Information: Drug-Gene Network
	Cross referenced IDs

Gene Summary for ME2

Basic gene info.	Gene symbol	ME2
	Gene name	malic enzyme 2, NAD(+)-dependent, mitochondrial
	Synonyms	ODS1
	Cytomap	UCSC genome browser: 18q21
	Genomic location	chr18 :48405431-48476162
	Type of gene	protein-coding
	RefGenes	NM_001168335.1, NM_002396.4,
	Ensembl id	ENSG00000082212
	Description	NAD-MENAD-dependent malic enzyme, mitochondrialmalate dehydrogenasepyruvic-malic carboxylase
	Modification date	20141207
dbXrefs	MIM : 154270
	HGNC : HGNC
	HPRD : 01103
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_ME2
	BioGPS: 4200
	Gene Expression Atlas: ENSG00000082212
	The Human Protein Atlas: ENSG00000082212
Pathway	NCI Pathway Interaction Database: ME2
	KEGG: ME2
	REACTOME: ME2
	ConsensusPathDB
	Pathway Commons: ME2
Metabolism	MetaCyc: ME2
	HUMANCyc: ME2
Regulation	Ensembl's Regulation: ENSG00000082212
	miRBase: chr18 :48,405,431-48,476,162
	TargetScan: NM_001168335
	cisRED: ENSG00000082212
Context	iHOP: ME2
	cancer metabolism search in PubMed: ME2
	UCL Cancer Institute: ME2
Assigned class in ccmGDB	C

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Phenotypic Information for ME2(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: ME2
	Familial Cancer Database: ME2

* This gene is included in those cancer gene databases.

						.
Oncogene ¹	Tumor Suppressor gene ²	Cancer Gene Census ³	CancerGenes ⁴	Network of Cancer Gene ⁵	Significant driver gene in	Therapeutic Vulnerabilities in Cancer¹

cf) number; DB name
1 Oncogene; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
2 Tumor Suppressor gene; https://bioinfo.uth.edu/TSGene/,
3 Cancer Gene Census; http://www.nature.com/nrc/journal/v4/n3/abs/nrc1299.html,
4 CancerGenes; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
5 Network of Cancer Gene; http://ncg.kcl.ac.uk/index.php,
1Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
KEGG_PYRUVATE_METABOLISM

Others
OMIM
Orphanet
Disease	KEGG Disease: ME2
	MedGen: ME2 (Human Medical Genetics with Condition)
	ClinVar: ME2
Phenotype	MGI: ME2 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: ME2

Mutations for ME2

* Under tables are showing count per each tissue to give us broad intuition about tissue specific mutation patterns.You can go to the detailed page for each mutation database's web site.

Structural Variants in COSMIC : go to COSMIC mutation histogram

- Statistics for Tissue and Mutation type

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- For Inter-chromosomal Variations

* Inter-chromosomal variantions includes 'interchromosomal amplicon to amplicon', 'interchromosomal amplicon to non-amplified dna', 'interchromosomal insertion', 'Interchromosomal unknown type'.

- For Intra-chromosomal Variations

* Intra-chromosomal variantions includes 'intrachromosomal amplicon to amplicon', 'intrachromosomal amplicon to non-amplified dna', 'intrachromosomal deletion', 'intrachromosomal fold-back inversion', 'intrachromosomal inversion', 'intrachromosomal tandem duplication', 'Intrachromosomal unknown type', 'intrachromosomal with inverted orientation', 'intrachromosomal with non-inverted orientation'.

Sample	Symbol_a	Chr_a	Start_a	End_a	Symbol_b	Chr_b	Start_b	End_b
ovary	ME2	chr18	48459343	48459363	DPP10	chr2	116168412	116168432
pancreas	ME2	chr18	48423105	48423125		chr18	48753811	48753831
pancreas	ME2	chr18	48450693	48450713		chr18	48614967	48614987
pancreas	ME2	chr18	48457900	48457920		chr18	48671485	48671505
pancreas	ME2	chr18	48461434	48461454		chr18	48815333	48815353

cf) Tissue number; Tissue name (1;Breast, 2;Central_nervous_system, 3;Haematopoietic_and_lymphoid_tissue, 4;Large_intestine, 5;Liver, 6;Lung, 7;Ovary, 8;Pancreas, 9;Prostate, 10;Skin, 11;Soft_tissue, 12;Upper_aerodigestive_tract)

Related fusion transcripts : go to Chitars2.0

* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows ME2 related fusion information.

Head Gene

Tail Gene

Accession

Gene_a

qStart_a

qEnd_a

Chromosome_a

tStart_a

tEnd_a

Gene_a

qStart_a

qEnd_a

Chromosome_a

tStart_a

tEnd_a

Other DBs for Structural Variants

Structural Variants in Ensembl: go to Ensembl Structural variation

Structural Variants in dbVar: go to dbVar

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Copy Number Variations in COSMIC : go to COSMIC mutation CNV/Expr

Mutation type/ Tissue ID

brca

cns

cerv

endome

haematopo

kidn

Lintest

liver

lung

ovary

pancre

prost

skin

stoma

thyro

urina

Total # sample

GAIN (# sample)

LOSS (# sample)

cf) Tissue ID; Tissue type (1; Breast, 2; Central_nervous_system, 3; Cervix, 4; Endometrium, 5; Haematopoietic_and_lymphoid_tissue, 6; Kidney, 7; Large_intestine, 8; Liver, 9; Lung, 10; NS, 11; Ovary, 12; Pancreas, 13; Prostate, 14; Skin, 15; Stomach, 16; Thyroid, 17; Urinary_tract)

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SNV Counts per Each Loci in COSMIC data : go to COSMIC point mutation

: Non-synonymous mutation, : Synonymous mutation, Circle size denotes number of samples.
Maximum mutation count=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=43)	Stat. for Synonymous SNVs (# total SNVs=15)

Stat. for Deletions (# total SNVs=0)	Stat. for Insertions (# total SNVs=0)
There's no deleted snv.	There's no inserted snv.

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Top 10 SNVs Having the Most Samples in COSMIC data

* When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site,primary_histology,mutation(aa),pubmedID.

GRCh37 position	Mutation(aa)	Unique sampleID count
chr18:48458685-48458685	p.R458*	3
chr18:48473521-48473521	p.E574E	3
chr18:48446853-48446853	p.F254F	3
chr18:48439207-48439207	p.E93D	2
chr18:48439240-48439240	p.I104M	2
chr18:48444557-48444557	p.D236D	2
chr18:48434431-48434431	p.?	2
chr18:48434439-48434439	p.A39T	2
chr18:48442553-48442553	p.S136S	2
chr18:48439180-48439180	p.Y84Y	1

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SNV Counts per Each Loci in TCGA data

: non-synonymous mutation, : synonymous mutation, Circle size denotes number of samples.
maximum mutation count=2

Point Mutation/ Tissue ID	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20
# sample		2		10	1		2		2	1		7	3				4	4		8
# mutation		2		9	1		2		2	1		10	3				4	4		11
nonsynonymous SNV		2		7	1		1		2	1		9	2				1	3		9
synonymous SNV				2			1					1	1				3	1		2

cf) Tissue ID; Tissue type (1; BLCA[Bladder Urothelial Carcinoma], 2; BRCA[Breast invasive carcinoma], 3; CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], 4; COAD[Colon adenocarcinoma], 5; GBM[Glioblastoma multiforme], 6; Glioma Low Grade, 7; HNSC[Head and Neck squamous cell carcinoma], 8; KICH[Kidney Chromophobe], 9; KIRC[Kidney renal clear cell carcinoma], 10; KIRP[Kidney renal papillary cell carcinoma], 11; LAML[Acute Myeloid Leukemia], 12; LUAD[Lung adenocarcinoma], 13; LUSC[Lung squamous cell carcinoma], 14; OV[Ovarian serous cystadenocarcinoma ], 15; PAAD[Pancreatic adenocarcinoma], 16; PRAD[Prostate adenocarcinoma], 17; SKCM[Skin Cutaneous Melanoma], 18:STAD[Stomach adenocarcinoma], 19:THCA[Thyroid carcinoma], 20:UCEC[Uterine Corpus Endometrial Carcinoma])

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Top 10 SNVs Having the Most Samples in TCGA data

* We represented just top 10 SNVs. When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site, primary_histology, mutation(aa), pubmedID.

Genomic Position	Mutation(aa)	Unique sampleID count
chr18:48422269	p.E93D,ME2	2
chr18:48434439	p.P27S,ME2	2
chr18:48439207	p.A39T,ME2	2
chr18:48439249	p.Y84Y,ME2	1
chr18:48473422	p.A293V,ME2	1
chr18:48447032	p.Q509K	1
chr18:48422209	p.R91T,ME2	1
chr18:48452221	p.I298I,ME2	1
chr18:48439273	p.A527S	1
chr18:48473427	p.E329Q,ME2	1

Other DBs for Point Mutations

Point Mutation Table of Ensembl: go to Ensembl variation table

Mutation of cBioPortal: go to cBioPortal's Cross-cancer alteration summary

Copy Number for ME2 in TCGA

* Copy number data were extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered on Jan-05-2015. Function ProcessCNAData in TCGA-Assembler package was used to obtain gene-level copy number value which is calculated as the average copy number of the genomic region of a gene.

cf) Tissue ID[Tissue type]: BLCA[Bladder Urothelial Carcinoma], BRCA[Breast invasive carcinoma], CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], COAD[Colon adenocarcinoma], GBM[Glioblastoma multiforme], Glioma Low Grade, HNSC[Head and Neck squamous cell carcinoma], KICH[Kidney Chromophobe], KIRC[Kidney renal clear cell carcinoma], KIRP[Kidney renal papillary cell carcinoma], LAML[Acute Myeloid Leukemia], LUAD[Lung adenocarcinoma], LUSC[Lung squamous cell carcinoma], OV[Ovarian serous cystadenocarcinoma ], PAAD[Pancreatic adenocarcinoma], PRAD[Prostate adenocarcinoma], SKCM[Skin Cutaneous Melanoma], STAD[Stomach adenocarcinoma], THCA[Thyroid carcinoma], UCEC[Uterine Corpus Endometrial Carcinoma]

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Gene Expression for ME2

Gene Expression in Cancer Cell-lines (CCLE)

* CCLE gene expression data were extracted from CCLE_Expression_Entrez_2012-10-18.res: Gene-centric RMA-normalized mRNA expression data.

Differential Gene Expression in Primary Tumors (TCGA)

* Normalized gene expression data of RNASeqV2 was extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered at Jan-05-2015. Only eight cancer types have enough normal control samples for differential expression analysis.
(t test, adjusted p<0.05 (using Benjamini-Hochberg FDR))

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CNV vs Gene Expression Plot

* This plots show the correlation between CNV and gene expression.

: Open all plots for all cancer types

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Gene-Gene Network Information

Co-Expressed gene's network Plot

* Co-Expression network figures were drawn using R package igraph. Only the top 20 genes with the highest correlations were shown.
Red circle: input gene, orange circle: cell metabolism gene, sky circle: other gene

: Open all plots for all cancer types


MB21D1,CENPA,DSC2,ELAC1,AMER1,FAM171A1,FOXM1, GPR63,MALT1,ME2,MEX3C,NARS,PUS7,R3HDM1, RAD51AP1,SKA1,SRPK1,SUV39H2,TAF4B,TEX10,WDR43	AP1S2,BTBD1,TCAIM,CAB39,CAMK2D,CAPZA2,EGLN1, GTPBP8,KPNA3,KPNA4,LOC653653,ME2,MEMO1,NAA50, OSBPL11,PLCL2,PPP3CB,RRAGD,SLC16A1,TM6SF1,TTL

ATP5A1,ATP5B,ATPAF2,TIMM21,C1QBP,CHAC2,CNDP2, DLST,EIF4A1,ELAC1,FECH,IER3IP1,KIAA1468,MBD2, ME2,NARS,PCCB,PIAS2,SCO1,SKA1,TXNL1	ABCD3,ABHD5,AKR1B10,DECR1,ECHS1,MICU2,ETFA, ETFDH,ETNK1,FAM107B,FAM45A,FDX1,GCLM,GHITM, ME2,MTCH2,NRAS,PITX2,SLMO2,TGFA,UGDH

Co-Expressed gene's Protein-protein interaction Network Plot

: Open all plots for all cancer types

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Interacting Genes (from Pathway Commons)

: Open all interacting genes' information including KEGG pathway for all interacting genes from DAVID

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Pharmacological Information for ME2

Cross-referenced pharmacological DB IDs from Uniprot

DB Category

DB Name

DB's ID and Url link

Drug-Gene Interaction Network

* Gene Centered Interaction Network.

* Drug Centered Interaction Network.

DrugBank ID	Target Name	Drug Groups	Generic Name	Drug Centered Network	Drug Structure
DB00157	malic enzyme 2, NAD(+)-dependent, mitochondrial	approved; nutraceutical	NADH
DB01677	malic enzyme 2, NAD(+)-dependent, mitochondrial	experimental	Fumarate
DB01907	malic enzyme 2, NAD(+)-dependent, mitochondrial	experimental	Nicotinamide-Adenine-Dinucleotide
DB03499	malic enzyme 2, NAD(+)-dependent, mitochondrial	experimental	Malate Ion
DB03589	malic enzyme 2, NAD(+)-dependent, mitochondrial	experimental	Alpha-Ketomalonic Acid
DB03680	malic enzyme 2, NAD(+)-dependent, mitochondrial	experimental	Tartronate

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Cross referenced IDs for ME2

* We obtained these cross-references from Uniprot database. It covers 150 different DBs, 18 categories. http://www.uniprot.org/help/cross_references_section

: Open all cross reference information