2014
Mitochondrial Disease Sequence Data Resource (MSeqDR): A global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities
Falk M, Shen L, Gonzalez M, Leipzig J, Lott M, Stassen A, Diroma M, Navarro-Gomez D, Yeske P, Bai R, Boles R, Brilhante V, Ralph D, DaRe J, Shelton R, Terry S, Zhang Z, Copeland W, van Oven M, Prokisch H, Wallace D, Attimonelli M, Krotoski D, Zuchner S, Gai X, participants: M, Bale S, Bedoyan J, Behar D, Bonnen P, Brooks L, Calabrese C, Calvo S, Chinnery P, Christodoulou J, Church D, Clima R, Cohen B, Cotton R, de Coo I, Derbenevoa O, Dunnen J, Dimmock D, Enns G, Gasparre G, Goldstein A, Gonzalez I, Gwinn K, Hahn S, Haas R, Hakonarson H, Hirano M, Kerr D, Li D, Lvova M, Macrae F, Maglott D, McCormick E, Mitchell G, Mootha V, Okazaki Y, Pujol A, Parisi M, Perin J, Pierce E, Procaccio V, Rahman S, Reddi H, Rehm H, Riggs E, Rodenburg R, Rubinstein Y, Saneto R, Santorsola M, Scharfe C, Sheldon C, Shoubridge E, Simone D, Smeets B, Smeitink J, Stanley C, Suomalainen A, Tarnopolsky M, Thiffault I, Thorburn D, Van Hove J, Wolfe L, Wong L. Mitochondrial Disease Sequence Data Resource (MSeqDR): A global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities. Molecular Genetics And Metabolism 2014, 114: 388-396. PMID: 25542617, PMCID: PMC4512182, DOI: 10.1016/j.ymgme.2014.11.016.Peer-Reviewed Original ResearchConceptsWeb portalData resourcesLocus-specific databasesAnnotation tracksData analysis needsResearch communityAnalysis toolsUnique identifier systemsCentral web portalMitochondrial diseaseCustom annotation tracksUser-friendly fashionData analysis toolsGenomic data analysisUser interrogationData of relevanceDataset curationData sharingData visualizationIdentifier systemVariant pathogenicity assessmentCentralized knowledgeAnalysis needsOntology toolsMSeqDRA functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system
Schlecht U, Suresh S, Xu W, Aparicio AM, Chu A, Proctor MJ, Davis RW, Scharfe C, St Onge RP. A functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system. BMC Genomics 2014, 15: 263. PMID: 24708151, PMCID: PMC4023593, DOI: 10.1186/1471-2164-15-263.Peer-Reviewed Original ResearchConceptsRespiratory growthFunctional screenCopper homeostasis genesHomozygous diploid deletionIntracellular copper concentrationList of genesComplex cellular systemsDeletion strainHomeostasis genesCopper homeostasisLow vacuolar pHDirect regulatorRespiratory defectsDifferent genesAerobic organismsIron uptakeFunctional linkMendelian disordersGenesCellular systemsGrowth mediumVacuolar pHHomeostasis resultsGenetic originHuman health
2012
Forward Chemical Genetics in Yeast for Discovery of Chemical Probes Targeting Metabolism
St.Onge R, Schlecht U, Scharfe C, Evangelista M. Forward Chemical Genetics in Yeast for Discovery of Chemical Probes Targeting Metabolism. Molecules 2012, 17: 13098-13115. PMID: 23128089, PMCID: PMC3539408, DOI: 10.3390/molecules171113098.Peer-Reviewed Original ResearchConceptsChemical geneticsChemical probesCellular metabolismDominant model organismChemical genetic screeningForward chemical geneticsHigh-throughput phenotypicDrug target identificationNormal cellular metabolismNew chemical probesHigher eukaryotesExperimental tractabilityModel organismsYeast SaccharomycesCellular processesIdeal organismNew druggable targetsMolecular biologyYeastDruggable targetsGeneticsDiseased statesOrganismsGenetic screeningMetabolism
2004
Integrative Analysis of the Mitochondrial Proteome in Yeast
Prokisch H, Scharfe C, Camp DG, Xiao W, David L, Andreoli C, Monroe ME, Moore RJ, Gritsenko MA, Kozany C, Hixson KK, Mottaz HM, Zischka H, Ueffing M, Herman ZS, Davis RW, Meitinger T, Oefner PJ, Smith RD, Steinmetz LM. Integrative Analysis of the Mitochondrial Proteome in Yeast. PLOS Biology 2004, 2: e160. PMID: 15208715, PMCID: PMC423137, DOI: 10.1371/journal.pbio.0020160.Peer-Reviewed Original ResearchConceptsMitochondrial proteomeGenomic approachesPhenotype screeningGenome-wide approachesSubcellular localization studiesComplex mitochondrial disordersDifferent genomic approachesProtein interaction analysisYeast mitochondriaMitochondrial proteinsMitochondrial organellesProteomic approachProteome studiesAbundant proteinsExpression analysisCandidate genesExpression profilingIntegrative analysisMitochondrial functionLocalization studiesOrganellesMitochondrial disordersProteinSystematic identificationMass spectrometry
2003
Role of duplicate genes in genetic robustness against null mutations
Gu Z, Steinmetz LM, Gu X, Scharfe C, Davis RW, Li WH. Role of duplicate genes in genetic robustness against null mutations. Nature 2003, 421: 63-66. PMID: 12511954, DOI: 10.1038/nature01198.Peer-Reviewed Original ResearchConceptsDuplicate genesGenetic robustnessNull mutationSevere fitness effectsGenome-wide evaluationAlternative metabolic pathwaysFitness effectsLoss of functionSequence similarityRegulatory networksDeletion mutantsS. cerevisiaeGenesMetabolic pathwaysDuplicate copiesGene deletionFunctional compensationFitness dataCopiesMutationsMutantsCerevisiaeRelative importanceOrganismsSecond mechanism
2001
Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients presenting with respiratory chain deficiencies
Jaksch M, Kleinle S, Scharfe C, Klopstock T, Pongratz D, Müller-Höcker J, Gerbitz KD, Liechti-Gallati S, Lochmuller H, Horvath R. Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients presenting with respiratory chain deficiencies. Journal Of Medical Genetics 2001, 38: 665. PMID: 11584044, PMCID: PMC1734743, DOI: 10.1136/jmg.38.10.665.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultChildChild, PreschoolDNA Mutational AnalysisElectron TransportFemaleGene FrequencyGenetic VariationGenotypeHumansInfantInfant, NewbornMaleMiddle AgedMitochondria, MuscleMitochondrial DiseasesMuscle, SkeletalMutationPhenotypePolymorphism, GeneticRNARNA, MitochondrialRNA, TransferSequence DeletionConceptsMitochondrial transfer RNA (mt-tRNA) mutationsAdult patientsRespiratory chain deficiencyDistinct neurological syndromesChain deficiencyNeonatal groupPediatric groupClinical symptomsNeurological syndromeIndex patientsPathogenic mitochondrial DNA mutationsPatientsPathogenic relevanceMitochondrial DNA mutationsSkeletal musclePathogenic mutationsMuscle DNARNA mutationsMitochondrial disordersG mutationSkeletal muscle DNADeficiencyDetection rateDNA mutationsRC deficiency