2024
Evolutionary druggability for low-dimensional fitness landscapes toward new metrics for antimicrobial applications
Guerrero R, Dorji T, Harris R, Shoulders M, Ogbunugafor C. Evolutionary druggability for low-dimensional fitness landscapes toward new metrics for antimicrobial applications. ELife 2024, 12: rp88480. PMID: 38833384, PMCID: PMC11149929, DOI: 10.7554/elife.88480.Peer-Reviewed Original ResearchConceptsDrug targetsAllelic variantsStanding genetic variationEmpirical fitness landscapesFitness landscapeGenetic variationB-lactamasePathogenic variantsTarget proteinsVariant sensitivityB-lactamAllelesDrug-target interactionsPathogensMutationsVariantsDrug environmentMechanistic insightDrug developmentMolecular properties of drugsAntimicrobial applicationsApplication metricsLociVariant variablesPharmacological interventionsEvolutionary druggability for low-dimensional fitness landscapes toward new metrics for antimicrobial applications
Guerrero R, Dorji T, Harris R, Shoulders M, Ogbunugafor C. Evolutionary druggability for low-dimensional fitness landscapes toward new metrics for antimicrobial applications. ELife 2024, 12 DOI: 10.7554/elife.88480.3.Peer-Reviewed Original ResearchDrug targetsAllelic variantsStanding genetic variationEmpirical fitness landscapesFitness landscapeGenetic variationB-lactamasePathogenic variantsTarget proteinsVariant sensitivityB-lactamAllelesDrug-target interactionsPathogensMutationsVariantsDrug environmentMechanistic insightDruggabilityDrug developmentMolecular properties of drugsAntimicrobial applicationsApplication metricsLociVariant variables
2019
Non-typeable Haemophilus influenzae isolates from patients with chronic obstructive pulmonary disease contain new phase-variable modA methyltransferase alleles controlling phasevarions
Atack JM, Murphy TF, Pettigrew MM, Seib KL, Jennings MP. Non-typeable Haemophilus influenzae isolates from patients with chronic obstructive pulmonary disease contain new phase-variable modA methyltransferase alleles controlling phasevarions. Scientific Reports 2019, 9: 15963. PMID: 31685916, PMCID: PMC6828955, DOI: 10.1038/s41598-019-52429-6.Peer-Reviewed Original ResearchConceptsNon-typeable Haemophilus influenzaeChronic obstructive pulmonary diseaseObstructive pulmonary diseaseMiddle ear infectionPulmonary diseaseEar infectionsNTHi strainsHaemophilus influenzaeExacerbation of COPDCOPDMiddle earPatientsAllele distributionInfectionInfluenzaeBacterial pathogensDiseaseMultiple allelic variantsAllelic variantsGene expressionAllelesEpigenetic mechanismsLarge panelExacerbationExpressionInferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming
Ohlin M, Scheepers C, Corcoran M, Lees WD, Busse CE, Bagnara D, Thörnqvist L, Bürckert JP, Jackson KJL, Ralph D, Schramm CA, Marthandan N, Breden F, Scott J, Matsen F, Greiff V, Yaari G, Kleinstein SH, Christley S, Sherkow JS, Kossida S, Lefranc MP, van Zelm MC, Watson CT, Collins AM. Inferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming. Frontiers In Immunology 2019, 10: 435. PMID: 30936866, PMCID: PMC6431624, DOI: 10.3389/fimmu.2019.00435.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBase SequenceDatabases, GeneticDatasets as TopicGene LibraryGenes, ImmunoglobulinGenetic VariationGerm-Line MutationHigh-Throughput Nucleotide SequencingHumansImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionPolymerase Chain ReactionSequence AlignmentSequence Homology, Nucleic AcidTerminology as TopicV(D)J RecombinationVDJ ExonsConceptsGene databaseInternational ImMunoGeneTics information systemAdaptive immune receptor repertoire sequencingLymphocyte receptor genesAllelic variantsGermline genesReceptor geneAIRR CommunityVertebrate speciesGenetic variationIg diversityAIRR-seq dataJ genesIg genesAllelic sequencesGenesIGHV genesEffector moleculesUnprecedented insightsB-cell lineageBiological interpretationT cell receptorReference databaseGene variationRepertoire studies
2016
A uniform survey of allele-specific binding and expression over 1000-Genomes-Project individuals
Chen J, Rozowsky J, Galeev TR, Harmanci A, Kitchen R, Bedford J, Abyzov A, Kong Y, Regan L, Gerstein M. A uniform survey of allele-specific binding and expression over 1000-Genomes-Project individuals. Nature Communications 2016, 7: 11101. PMID: 27089393, PMCID: PMC4837449, DOI: 10.1038/ncomms11101.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsBinding SitesChromosome MappingComputational BiologyDatabases, GeneticGene ExpressionGene FrequencyGenome, HumanGenomicsGenotypeHigh-Throughput Nucleotide SequencingHuman Genome ProjectHumansInternetMolecular Sequence AnnotationPolymorphism, Single NucleotidePrecision MedicineConceptsSingle nucleotide variantsAllele-specific bindingFunctional genomics data setsAllele-specific behaviorLarge-scale sequencingGenomic data setsAllelic imbalanceNumber of readsChIP-seqRNA-seqGenome ProjectMaternal chromosomesNucleotide variantsPersonal genomesMapping biasAllelic variantsVariant catalogMultiple individualsFunctional effectsProject individualsBindingExpressionVariantsGenomeChromosomes
2012
Fanconi-Bickel Syndrome and Autosomal Recessive Proximal Tubulopathy with Hypercalciuria (ARPTH) Are Allelic Variants Caused by GLUT2 Mutations
Mannstadt M, Magen D, Segawa H, Stanley T, Sharma A, Sasaki S, Bergwitz C, Mounien L, Boepple P, Thorens B, Zelikovic I, Jüppner H. Fanconi-Bickel Syndrome and Autosomal Recessive Proximal Tubulopathy with Hypercalciuria (ARPTH) Are Allelic Variants Caused by GLUT2 Mutations. The Journal Of Clinical Endocrinology & Metabolism 2012, 97: e1978-e1986. PMID: 22865906, PMCID: PMC3462928, DOI: 10.1210/jc.2012-1279.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceAnimalsFamilial Hypophosphatemic RicketsFamily HealthFanconi SyndromeFemaleGenes, RecessiveGenetic VariationGenome-Wide Association StudyGlucose Transporter Type 1Glucose Transporter Type 2HumansHypercalciuriaHypophosphatemia, FamilialKidney Tubules, ProximalMaleMiceMice, TransgenicMolecular Sequence DataOocytesPedigreeRicketsSodium-Phosphate Cotransporter Proteins, Type IIaSodium-Phosphate Cotransporter Proteins, Type IIcXenopus laevisConceptsGlucose transporter 2Sequence analysis of candidate genesCandidate genesSequence analysisGenome-wide linkage scanAnalysis of candidate genesFanconi-Bickel syndromeProximal renal tubulopathyRenal tubulopathyNucleotide sequence analysisGenetic mappingHomozygous mutationPhosphate importLinkage scanMolecular basisXenopus oocytesTransport of glucoseGLUT2 mutationsMolecular levelGenesGlucose transportUrinary phosphate excretionAllelic variantsPhosphate homeostasisDirect nucleotide sequence analysis
2011
The CD6 Multiple Sclerosis Susceptibility Allele Is Associated with Alterations in CD4+ T Cell Proliferation
Kofler DM, Severson CA, Mousissian N, De Jager PL, Hafler DA. The CD6 Multiple Sclerosis Susceptibility Allele Is Associated with Alterations in CD4+ T Cell Proliferation. The Journal Of Immunology 2011, 187: 3286-3291. PMID: 21849685, DOI: 10.4049/jimmunol.1100626.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAntigens, CDAntigens, Differentiation, T-LymphocyteCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell ProliferationCell SeparationCells, CulturedFemaleFlow CytometryGenetic Predisposition to DiseaseGenotypeHumansMaleMultiple SclerosisPhenotypeReverse Transcriptase Polymerase Chain ReactionRisk FactorsRNA, Small InterferingConceptsGenome-wide association studiesAssociation studiesAllelic variantsNew susceptibility lociSusceptibility allelesRisk allelesProliferation defectExon 5Risk-associated allelesSingle nucleotide polymorphismsExtracellular binding sitesCD6 geneSusceptibility lociLinkage disequilibriumMS risk alleleSelective knockdownT cell activationNucleotide polymorphismsAltered proliferationCell proliferationGenetic associationAllelesLong-term activationBinding sitesMS susceptibility alleles
2009
Autoimmunity risk alleles in costimulation pathways
Maier LM, Hafler DA. Autoimmunity risk alleles in costimulation pathways. Immunological Reviews 2009, 229: 322-336. PMID: 19426231, DOI: 10.1111/j.1600-065x.2009.00777.x.Peer-Reviewed Original ResearchConceptsTumor necrosis factorGenome-wide association scansHuman autoimmune diseasesAutoimmune diseasesCommon human autoimmune diseasesInducible T-cell costimulator ligandGenetic study designsAssociation scanImmune related genesRelated genesCytotoxic T-lymphocyte antigen-4T-lymphocyte antigen-4Common autoimmune diseaseCell death 1Allelic variantsMember 15Environmental risk factorsDrug designCostimulatory mechanismsMember 4PathwayGenesCostimulation pathwayDeath-1Common pathway
2008
Lysosomal Cysteine and Aspartic Proteases Are Heterogeneously Expressed and Act Redundantly to Initiate Human Invariant Chain Degradation
Costantino CM, Hang HC, Kent SC, Hafler DA, Ploegh HL. Lysosomal Cysteine and Aspartic Proteases Are Heterogeneously Expressed and Act Redundantly to Initiate Human Invariant Chain Degradation. The Journal Of Immunology 2008, 180: 2876-2885. PMID: 18292509, DOI: 10.4049/jimmunol.180.5.2876.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigen PresentationAntigens, Differentiation, B-LymphocyteAspartic Acid EndopeptidasesB-LymphocytesCD4-Positive T-LymphocytesCell Line, TransformedClone CellsCoculture TechniquesCysteine EndopeptidasesGene Expression Regulation, EnzymologicGenetic HeterogeneityHistocompatibility Antigens Class IIHLA-D AntigensHumansLysosomesMolecular Sequence DataProtease InhibitorsProtein Processing, Post-TranslationalConceptsAsparagine endopeptidasePeptide AgClass II MHC productsMyelin basic protein epitopeClass II MHCClass II invariant chainInvariant chain cleavageInvariant chain degradationPresentation of AgInvariant chain processingAEP inhibitionB cell linesDistinct allelic variantsII MHCMHC productsDifferent EBVMHC dimersAllelic variantsHuman AgInvariant chainAltered regulation
2007
Allelic variant in CTLA4 alters T cell phosphorylation patterns
Maier LM, Anderson DE, De Jager PL, Wicker LS, Hafler DA. Allelic variant in CTLA4 alters T cell phosphorylation patterns. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 18607-18612. PMID: 18000051, PMCID: PMC2141824, DOI: 10.1073/pnas.0706409104.Peer-Reviewed Original ResearchConceptsT cell antigen receptorAllelic variationMemory T cellsAutoimmune diseasesCell antigen receptorT cell signalingT cellsFunctional effectsDisease susceptibility allelesCell signalingPhosphorylation patternPhosphorylation levelsSusceptibility variantsTCR stimulationAllelic variantsHuman immune cellsAntigen receptorGenesImmune cellsHealthy individualsCTLA4 geneCellsSpecific mAbsCTLA4DiseaseSignatures of strong population differentiation shape extended haplotypes across the human CD28, CTLA4, and ICOS costimulatory genes
Butty V, Roy M, Sabeti P, Besse W, Benoist C, Mathis D. Signatures of strong population differentiation shape extended haplotypes across the human CD28, CTLA4, and ICOS costimulatory genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 570-575. PMID: 17197413, PMCID: PMC1766426, DOI: 10.1073/pnas.0610124104.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, DifferentiationAntigens, Differentiation, T-LymphocyteAutoimmunityCD28 AntigensChromosomes, Human, Pair 2CTLA-4 AntigenEthnicityGenetic VariationGenetics, PopulationHaplotypesHumansInducible T-Cell Co-Stimulator ProteinLinkage DisequilibriumLymphocyte ActivationPolymorphism, Single NucleotidePromoter Regions, GeneticT-LymphocytesConceptsLong-range linkage disequilibriumShort genomic intervalsGenomic intervalsCourse of human migrationsDemographic eventsDNA panelLinkage disequilibriumReceptor familyHuman CD28T cell activationMicrobial challengeAllelic variantsHuman populationHaplotypesDifferentiation shapeGenesLociCell activationHuman migrationUnusual differencesCostimulatory genesExtended haplotypesVariantsGeographic regionsCTLA-4
2002
A second kindred linked to DFNA20 (17q25.3) reduces the genetic interval
DeWan A, Parrado A, Leal S. A second kindred linked to DFNA20 (17q25.3) reduces the genetic interval. Clinical Genetics 2002, 63: 39-45. PMID: 12519370, PMCID: PMC6143177, DOI: 10.1034/j.1399-0004.2003.630106.x.Peer-Reviewed Original Research
1994
Detection of DNA sequence variation via deliberate heteroduplex formation from genomic DNAs amplified en masse in "population tubes".
Ruano G, Deinard A, Tishkoff S, Kidd K. Detection of DNA sequence variation via deliberate heteroduplex formation from genomic DNAs amplified en masse in "population tubes". Genome Research 1994, 3: 225-231. PMID: 8173512, DOI: 10.1101/gr.3.4.225.Peer-Reviewed Original ResearchConceptsDNA sequence variationSequence variationGenomic DNAGlucose-6-phosphate dehydrogenase geneX chromosome lociWide geographic distributionLarge-scale samplingLong intronsDehydrogenase geneAllelic variationHeteroduplex moleculesGeographic distributionAllelic variantsHeteroduplex formationChimpanzee samplesHuman populationGradient electrophoresisRare variantsDNAGradient gelsHeteroduplexesElectrophoresisIntronsGenesLoci
1992
Truncation variants of peptides isolated from MHC class II molecules suggest sequence motifs
Rudensky A, Preston-Hurlburt, P, Al-Ramadi B, Rothbard J, Janeway C. Truncation variants of peptides isolated from MHC class II molecules suggest sequence motifs. Nature 1992, 359: 429-431. PMID: 1328884, DOI: 10.1038/359429a0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigen-Antibody ReactionsBacterial ProteinsBinding Sites, AntibodyCell LineChromatography, High Pressure LiquidHistocompatibility Antigens Class IIImmunoglobulin GImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionMiceMice, Inbred C57BLMolecular Sequence DataPeptide FragmentsReceptors, TransferrinRepressor ProteinsSequence AlignmentSequence Homology, Amino AcidT-LymphocytesViral Envelope ProteinsConceptsMHC class II moleculesClass II moleculesMHC class IMajor histocompatibility complexCD4 T cell recognitionClass IForeign protein antigensMHC class IIT cell recognitionT cellsMHC moleculesClass IIProtein antigensHistocompatibility complexAntigenic peptidesOuter aspectPeptide-binding cleftAmino acid differencesAnchor residuesAllelic variantsSingle peptide sequenceDifferent allelic formsPeptidesTruncation variantsAllelic forms
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