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 DLAT

Basic gene info.	Gene symbol	DLAT
	Gene name	dihydrolipoamide S-acetyltransferase
	Synonyms	DLTA\|PDC-E2\|PDCE2
	Cytomap	UCSC genome browser: 11q23.1
	Genomic location	chr11 :111895537-111935002
	Type of gene	protein-coding
	RefGenes	NM_001931.4,
	Ensembl id	ENSG00000263032
	Description	70 kDa mitochondrial autoantigen of primary biliary cirrhosisE2 component of pyruvate dehydrogenase complexM2 antigen complex 70 kDa subunitPBCdihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complexdihydrolipoyllysine-residue a
	Modification date	20141207
dbXrefs	MIM : 608770
	HGNC : HGNC
	Ensembl : ENSG00000150768
	HPRD : 10578
	Vega : OTTHUMG00000133751
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_DLAT
	BioGPS: 1737
	Gene Expression Atlas: ENSG00000263032
	The Human Protein Atlas: ENSG00000263032
Pathway	NCI Pathway Interaction Database: DLAT
	KEGG: DLAT
	REACTOME: DLAT
	ConsensusPathDB
	Pathway Commons: DLAT
Metabolism	MetaCyc: DLAT
	HUMANCyc: DLAT
Regulation	Ensembl's Regulation: ENSG00000263032
	miRBase: chr11 :111,895,537-111,935,002
	TargetScan: NM_001931
	cisRED: ENSG00000263032
Context	iHOP: DLAT
	cancer metabolism search in PubMed: DLAT
	UCL Cancer Institute: DLAT
Assigned class in ccmGDB	C

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

Cancer Description
Cancer	CGAP: DLAT
	Familial Cancer Database: DLAT

* 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_GLYCOLYSIS_GLUCONEOGENESIS KEGG_PYRUVATE_METABOLISM REACTOME_PYRUVATE_METABOLISM_AND_CITRIC_ACID_TCA_CYCLE REACTOME_PYRUVATE_METABOLISM

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

Mutations for DLAT

* 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

There's no inter-chromosomal structural variation.

- 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
breast	DLAT	chr11	111932285	111932285	IL18	chr11	112030719	112030719

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 DLAT related fusion information.

ID	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
AI022776	SPTB	34	154	14	65318952	65319074	DLAT	149	313	11	111896173	111896337
AL079484	DLAT	24	97	11	111933848	111933924	DLAT	87	462	11	111933916	111934296
H49884	DLAT	11	189	11	111896173	111896352	SPTB	184	293	14	65318966	65319074

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

There's no copy number variation information in COSMIC data for this gene.

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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=30)	Stat. for Synonymous SNVs (# total SNVs=12)

Stat. for Deletions (# total SNVs=3)	Stat. for Insertions (# total SNVs=1)

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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
chr11:111896927-111896927	p.P95P	3
chr11:111896324-111896324	p.A43V	3
chr11:111904183-111904183	p.E239G	3
chr11:111896360-111896360	p.V55G	2
chr11:111922036-111922036	p.E493K	2
chr11:111899524-111899524	p.D172A	2
chr11:111915910-111915910	p.P416S	2
chr11:111899614-111899614	p.S202L	2
chr11:111904177-111904177	p.R237T	2
chr11:111910097-111910097	p.G369W	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=3

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	1			4	1		2		2			6	3	1			4	5	1	4
# mutation	1			4	1		2		2			8	3	1			4	5	1	4
nonsynonymous SNV	1			4			1		1			6	1	1			1	5	1	3
synonymous SNV					1		1		1			2	2				3			1

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
chr11:111922036	p.S202L	2
chr11:111899614	p.E493K	2
chr11:111896434	p.G168G	1
chr11:111908010	p.I423I	1
chr11:111922022	p.I450I	1
chr11:111896990	p.P187R	1
chr11:111909992	p.K466T	1
chr11:111922035	p.A198D	1
chr11:111899361	p.G470V	1
chr11:111910068	p.C488F	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 DLAT 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 DLAT

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


AASDHPPT,ALG9,ARCN1,C11orf57,CHEK1,CUL5,DDX10, DLAT,EI24,EXPH5,NPAT,PAFAH1B2,RBM7,RDX, RNF214,SDHD,STT3A,TMEM123,UBE4A,USP28,ZW10	ALPK3,ATP5B,CHCHD3,DLAT,DLD,ETFDH,IMMT, MRS2,PDHA1,PDHB,PDHX,PGM1,PPM1B,SDHD, SGCG,SLC2A4,SLC2A5,SLC6A8,SOX6,TBX15,UQCRC2

ACAT1,CHCHD4,CHEK1,DLAT,DPAGT1,FASTKD1,GFM1, HSPA9,IMMT,LRPPRC,MTCH2,NCAPD3,NDUFS1,PDE12, PDHX,SDHB,SDHD,NDC1,TMX2,UCHL5,ZW10	CENPN,DBF4,DLAT,DPH2,EIF4A3,FAM136A,FARSB, FASTKD1,FH,GOT1,HSPA9,MIPEP,MRPL35,PDHX, PIGW,PPIF,QRSL1,SEH1L,TBRG4,TDG,WDR12

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 DLAT

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	dihydrolipoamide S-acetyltransferase	approved; nutraceutical	NADH
DB03758	dihydrolipoamide S-acetyltransferase	experimental	Radicicol
DB03760	dihydrolipoamide S-acetyltransferase	experimental	Dihydrolipoic Acid

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Cross referenced IDs for DLAT

* 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