2023
Lineage-specific genes are clustered with HET-domain genes and respond to environmental and genetic manipulations regulating reproduction in Neurospora
Wang Z, Wang Y, Kasuga T, Lopez-Giraldez F, Zhang Y, Zhang Z, Wang Y, Dong C, Sil A, Trail F, Yarden O, Townsend J. Lineage-specific genes are clustered with HET-domain genes and respond to environmental and genetic manipulations regulating reproduction in Neurospora. PLOS Genetics 2023, 19: e1011019. PMID: 37934795, PMCID: PMC10684091, DOI: 10.1371/journal.pgen.1011019.Peer-Reviewed Original ResearchConceptsLineage-specific genesHET domain genesSexual reproductionFunctional roleUnusual carbon sourcesPotential functional roleMating lociAsexual growthGenetic mutantsNeurospora crassaPossible functional roleSexual phaseGenetic manipulationTranscriptomic profilingReproduction regulationGene knockoutPP-1ADV-1Environmental alterationsGenesSexual developmentNeurosporaReproductionCarbon sourceGenetic barrier
2022
Differential Expression of Cell Wall Remodeling Genes Is Part of the Dynamic Phase-Specific Transcriptional Program of Conidial Germination of Trichoderma asperelloides
Gortikov M, Yakubovich E, Wang Z, López-Giráldez F, Tu Y, Townsend JP, Yarden O. Differential Expression of Cell Wall Remodeling Genes Is Part of the Dynamic Phase-Specific Transcriptional Program of Conidial Germination of Trichoderma asperelloides. Journal Of Fungi 2022, 8: 854. PMID: 36012842, PMCID: PMC9410309, DOI: 10.3390/jof8080854.Peer-Reviewed Original ResearchPolar growthTranscript abundanceConidial germinationGlucanase-encoding geneOnset of germinationTranscriptional hubsTranscriptional programsTrichoderma asperelloidesHyphal growthTranscriptional profilesDevelopmental eventsChitin synthaseHost recognitionDifferential expressionGerminationSpecific membersDormant conidiaFirst branchingGenomeGenesInitial branchingAbundanceNetwork analysisExpressionMorphological progressionWhole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia
Dong W, Wong KHY, Liu Y, Levy-Sakin M, Hung WC, Li M, Li B, Jin SC, Choi J, Lopez-Giraldez F, Vaka D, Poon A, Chu C, Lao R, Balamir M, Movsesyan I, Malloy MJ, Zhao H, Kwok PY, Kane JP, Lifton RP, Pullinger CR. Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia. Journal Of Lipid Research 2022, 63: 100209. PMID: 35460704, PMCID: PMC9126845, DOI: 10.1016/j.jlr.2022.100209.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingCandidate genesDamaging variantsGenome-wide association studiesGenome-wide significanceDamaging rare variantsCandidate gene listGene burden testingHDL-C levelsGene variantsGene listsAssociation studiesLDLR geneGenesBurden testingCancer biologySequencingFunction variantsABCA1Mean HDL-C levelsRare variantsDiscovery studiesCoronary heart diseaseHDL deficiencyRisk of cancerCenters for Mendelian Genomics: A decade of facilitating gene discovery
Baxter SM, Posey JE, Lake NJ, Sobreira N, Chong JX, Buyske S, Blue EE, Chadwick LH, Coban-Akdemir ZH, Doheny KF, Davis CP, Lek M, Wellington C, Jhangiani SN, Gerstein M, Gibbs RA, Lifton RP, MacArthur DG, Matise TC, Lupski JR, Valle D, Bamshad MJ, Hamosh A, Mane S, Nickerson DA, Consortium C, Adams M, Aguet F, Akay G, Anderson P, Antonescu C, Arachchi H, Atik M, Austin-Tse C, Babb L, Bacus T, Bahrambeigi V, Balasubramanian S, Bayram Y, Beaudet A, Beck C, Belmont J, Below J, Bilguvar K, Boehm C, Boerwinkle E, Boone P, Bowne S, Brand H, Buckingham K, Byrne A, Calame D, Campbell I, Cao X, Carvalho C, Chander V, Chang J, Chao K, Chinn I, Clarke D, Collins R, Cummings B, Dardas Z, Dawood M, Delano K, DiTroia S, Doddapaneni H, Du H, Du R, Duan R, Eldomery M, Eng C, England E, Evangelista E, Everett S, Fatih J, Felsenfeld A, Francioli L, Frazar C, Fu J, Gamarra E, Gambin T, Gan W, Gandhi M, Ganesh V, Garimella K, Gauthier L, Giroux D, Gonzaga-Jauregui C, Goodrich J, Gordon W, Griffith S, Grochowski C, Gu S, Gudmundsson S, Hall S, Hansen A, Harel T, Harmanci A, Herman I, Hetrick K, Hijazi H, Horike-Pyne M, Hsu E, Hu J, Huang Y, Hurless J, Jahl S, Jarvik G, Jiang Y, Johanson E, Jolly A, Karaca E, Khayat M, Knight J, Kolar J, Kumar S, Lalani S, Laricchia K, Larkin K, Leal S, Lemire G, Lewis R, Li H, Ling H, Lipson R, Liu P, Lovgren A, López-Giráldez F, MacMillan M, Mangilog B, Mano S, Marafi D, Marosy B, Marshall J, Martin R, Marvin C, Mawhinney M, McGee S, McGoldrick D, Mehaffey M, Mekonnen B, Meng X, Mitani T, Miyake C, Mohr D, Morris S, Mullen T, Murdock D, Murugan M, Muzny D, Myers B, Neira J, Nguyen K, Nielsen P, Nudelman N, O’Heir E, O’Leary M, Ongaco C, Orange J, Osei-Owusu I, Paine I, Pais L, Paschall J, Patterson K, Pehlivan D, Pelle B, Penney S, Chavez J, Pierce-Hoffman E, Poli C, Punetha J, Radhakrishnan A, Richardson M, Rodrigues E, Roote G, Rosenfeld J, Ryke E, Sabo A, Sanchez A, Schrauwen I, Scott D, Sedlazeck F, Serrano J, Shaw C, Shelford T, Shively K, Singer-Berk M, Smith J, Snow H, Snyder G, Solomonson M, Son R, Song X, Stankiewicz P, Stephan T, Sutton V, Sveden A, Sánchez D, Tackett M, Talkowski M, Threlkeld M, Tiao G, Udler M, Vail L, Valivullah Z, Valkanas E, VanNoy G, Wang Q, Wang G, Wang L, Wangler M, Watts N, Weisburd B, Weiss J, Wheeler M, White J, Williamson C, Wilson M, Wiszniewski W, Withers M, Witmer D, Witzgall L, Wohler E, Wojcik M, Wong I, Wood J, Wu N, Xing J, Yang Y, Yi Q, Yuan B, Zeiger J, Zhang C, Zhang P, Zhang Y, Zhang X, Zhang Y, Zhang S, Zoghbi H, van den Veyver I, Rehm H, O’Donnell-Luria A. Centers for Mendelian Genomics: A decade of facilitating gene discovery. Genetics In Medicine 2022, 24: 784-797. PMID: 35148959, PMCID: PMC9119004, DOI: 10.1016/j.gim.2021.12.005.Peer-Reviewed Original ResearchConceptsGene discoveryMendelian GenomicsUnderstanding of genesGene-phenotype relationshipsGenome variationWorldwide data sharingCandidate genesMendelian phenotypesGenomic researchGenome sequencingMatchmaker ExchangeGenomicsGenesSequencingBiomedical researchMajor roleDiscoveryExomePhenotypeRoleGenotypesCommunity
2021
CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling
Qin L, Zhang H, Li B, Jiang Q, Lopez F, Min W, Zhou JH. CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling. Arteriosclerosis Thrombosis And Vascular Biology 2021, 41: 2943-2960. PMID: 34670407, PMCID: PMC8613000, DOI: 10.1161/atvbaha.121.316707.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCells, CulturedEndothelial CellsEndothelium, LymphaticFemaleGene DeletionHemangioma, Cavernous, Central Nervous SystemHyperplasiaMaleMAP Kinase Signaling SystemMice, Inbred StrainsModels, AnimalNF-kappa BTranslocation, GeneticVascular Endothelial Growth Factor Receptor-3ConceptsLymphatic ECsLymphatic defectsCerebral cavernous malformationsPan-endothelial cellsGrowth factor receptorTranscriptional levelTransport assaysLymphatic hyperplasiaCCM genesLymphatic dysfunctionNuclear translocationGenesFactor receptorVEGFR3ERK1/2Nuclear factorDeletionEC proliferationInhibition of VEGFR3Dependent mannerVascular endothelial growth factor receptorEndothelial growth factor receptorEC deletionAbnormal valve structureKPNA2
2020
Comparative Genomics within and across Bilaterians Illuminates the Evolutionary History of ALK and LTK Proto-Oncogene Origination and Diversification
Dornburg A, Wang Z, Wang J, Mo ES, López-Giráldez F, Townsend JP. Comparative Genomics within and across Bilaterians Illuminates the Evolutionary History of ALK and LTK Proto-Oncogene Origination and Diversification. Genome Biology And Evolution 2020, 13: evaa228. PMID: 33196781, PMCID: PMC7851593, DOI: 10.1093/gbe/evaa228.Peer-Reviewed Original ResearchConceptsLeukocyte tyrosine kinaseEvolutionary historyPhylogenetic analysisProtein-coding genesComparative genomic analysisEarly embryonic expressionMetazoan genomesComparative genomicsPhylogenetic contextModel organismsEmbryonic expressionModel speciesHuman genesKey genesGenomic analysisImportant genesMammal systemsFunctional convergenceTyrosine kinaseMolecular homologyGenesFunctional roleVertebratesMammal modelsHomologyAlternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome
Dyment DA, O'Donnell‐Luria A, Agrawal PB, Akdemir Z, Aleck KA, Antaki D, Al Sharhan H, Au P, Aydin H, Beggs AH, Bilguvar K, Boerwinkle E, Brand H, Brownstein CA, Buyske S, Chodirker B, Choi J, Chudley AE, Clericuzio CL, Cox GF, Curry C, de Boer E, de Vries B, Dunn K, Dutmer CM, England EM, Fahrner JA, Geckinli BB, Genetti CA, Gezdirici A, Gibson WT, Gleeson JG, Greenberg CR, Hall A, Hamosh A, Hartley T, Jhangiani SN, Karaca E, Kernohan K, Lauzon JL, Lewis MES, Lowry RB, López‐Giráldez F, Matise TC, McEvoy‐Venneri J, McInnes B, Mhanni A, Minaur S, Moilanen J, Nguyen A, Nowaczyk MJM, Posey JE, Õunap K, Pehlivan D, Pajusalu S, Penney LS, Poterba T, Prontera P, Doriqui MJR, Sawyer SL, Sobreira N, Stanley V, Torun D, Wargowski D, Witmer PD, Wong I, Xing J, Zaki MS, Zhang Y, Consortium C, Genomics C, Boycott KM, Bamshad MJ, Nickerson DA, Blue EE, Innes AM. Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome. American Journal Of Medical Genetics Part A 2020, 185: 119-133. PMID: 33098347, PMCID: PMC8197629, DOI: 10.1002/ajmg.a.61926.Peer-Reviewed Original ResearchConceptsGenome sequencingExtensive locus heterogeneityCopy number variationsGenomic analysisMolecular diagnosisSingle geneDe novo variantsNext-generation sequencingDisease genesWide sequencingGenesGenomic diagnosisLocus heterogeneityNovo variantsSequencingPhenotypeAdditional familiesBiallelic variantsHDAC8FamilyVariant filteringDistinctive facial appearanceClinical phenotypeVariantsUncertain significance
2018
Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation
Duran D, Zeng X, Jin SC, Choi J, Nelson-Williams C, Yatsula B, Gaillard J, Furey CG, Lu Q, Timberlake AT, Dong W, Sorscher MA, Loring E, Klein J, Allocco A, Hunt A, Conine S, Karimy JK, Youngblood MW, Zhang J, DiLuna ML, Matouk CC, Mane S, Tikhonova IR, Castaldi C, López-Giráldez F, Knight J, Haider S, Soban M, Alper SL, Komiyama M, Ducruet AF, Zabramski JM, Dardik A, Walcott BP, Stapleton CJ, Aagaard-Kienitz B, Rodesch G, Jackson E, Smith ER, Orbach DB, Berenstein A, Bilguvar K, Vikkula M, Gunel M, Lifton RP, Kahle KT. Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation. Neuron 2018, 101: 429-443.e4. PMID: 30578106, PMCID: PMC10292091, DOI: 10.1016/j.neuron.2018.11.041.Peer-Reviewed Original ResearchConceptsChromatin modifiersVascular developmentSpecification of arteriesDeep venous systemNormal vascular developmentParent-offspring triosSignaling GenesGalen malformationDamaging mutationsGenesMutationsEssential roleArterio-venous malformationsCutaneous vascular abnormalitiesNovo mutationsExome sequencingDisease biologyIncomplete penetranceVariable expressivityVascular abnormalitiesVenous systemMutation carriersArterial bloodMutation burdenClinical implicationsLvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira
Adhikarla H, Wunder EA, Mechaly AE, Mehta S, Wang Z, Santos L, Bisht V, Diggle P, Murray G, Adler B, Lopez F, Townsend JP, Groisman E, Picardeau M, Buschiazzo A, Ko AI. Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira. Frontiers In Cellular And Infection Microbiology 2018, 8: 45. PMID: 29600195, PMCID: PMC5863495, DOI: 10.3389/fcimb.2018.00045.Peer-Reviewed Original ResearchConceptsResponse regulatorTwo-component system proteinsDNA-binding response regulatorGlobal transcriptional regulationHybrid histidine kinaseGlobal gene regulationNovel signal pathwayComprehensive genomic analysisPhosphotransfer assaysTCS genesHistidine kinaseGene duplicationTranscriptional regulationGene regulationCorresponding genesPhylogenetic analysisGenomic analysisMolecular basisMutant strainSystem proteinsSignaling systemInfection processGenesBranched pathwayVirulence
2015
The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities
Chong JX, Buckingham KJ, Jhangiani SN, Boehm C, Sobreira N, Smith JD, Harrell TM, McMillin MJ, Wiszniewski W, Gambin T, Akdemir Z, Doheny K, Scott AF, Avramopoulos D, Chakravarti A, Hoover-Fong J, Mathews D, Witmer PD, Ling H, Hetrick K, Watkins L, Patterson KE, Reinier F, Blue E, Muzny D, Kircher M, Bilguvar K, López-Giráldez F, Sutton VR, Tabor HK, Leal SM, Gunel M, Mane S, Gibbs RA, Boerwinkle E, Hamosh A, Shendure J, Lupski JR, Lifton RP, Valle D, Nickerson DA, Genomics C, Bamshad MJ. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities. American Journal Of Human Genetics 2015, 97: 199-215. PMID: 26166479, PMCID: PMC4573249, DOI: 10.1016/j.ajhg.2015.06.009.Peer-Reviewed Original ResearchConceptsMendelian phenotypesGenetic basisLarge-scale whole-exome sequencingMendelian conditionsGene functionGene regulationGenomic dataWhole-exome sequencingMendelian GenomicsGenesPhenotypic characterizationNovel mechanismExtensive clinical variabilityGenetic variantsPhenotypePervasive sharingBiological mechanismsSequencingNew therapeuticsSuch discoveriesFamilyDiscoveryHuman healthGenomicsClinical variability
2014
A Locus Encompassing the Epstein-Barr Virus bglf4 Kinase Regulates Expression of Genes Encoding Viral Structural Proteins
El-Guindy A, Lopez-Giraldez F, Delecluse HJ, McKenzie J, Miller G. A Locus Encompassing the Epstein-Barr Virus bglf4 Kinase Regulates Expression of Genes Encoding Viral Structural Proteins. PLOS Pathogens 2014, 10: e1004307. PMID: 25166506, PMCID: PMC4148442, DOI: 10.1371/journal.ppat.1004307.Peer-Reviewed Original ResearchConceptsLate gene expressionViral DNA replicationLate genesDNA replicationGene expressionOnly protein kinaseEBV transcriptomeDNA tumor virusesPost-replication eventsViral structural proteinsViral structural componentsWild-type Epstein-Barr virusProtein kinaseEctopic expressionKinase geneControl expressionTranscript levelsKinase activityMRNA-seqBGLF4Structural proteinsRegulate expressionGenesControl lociTumor virus
2013
Phylogenetic and phylogenomic overview of the Polyporales
Binder M, Justo A, Riley R, Salamov A, Lopez-Giraldez F, Sjökvist E, Copeland A, Foster B, Sun H, Larsson E, Larsson KH, Townsend J, Grigoriev IV, Hibbett DS. Phylogenetic and phylogenomic overview of the Polyporales. Mycologia 2013, 105: 1350-1373. PMID: 23935031, DOI: 10.3852/13-003.Peer-Reviewed Original ResearchConceptsSingle-copy genePhylogenetic informativeness analysesResidual polyporoid cladeBayesian phylogenetic analysisPolyporales speciesMajor lineagesPhylogenomic datasetsAvailable genomesCorresponding cladesPhlebioid cladePolyporoid cladeNew genomesGenome dataPhylogenetic analysisSuprageneric taxonomyCertain taxaPhylogenetic systematicsGenomic datasetsIdentical topologiesPolyporalesGenomeCladeSupport valuesGenesLineagesEvaluating Phylogenetic Informativeness as a Predictor of Phylogenetic Signal for Metazoan, Fungal, and Mammalian Phylogenomic Data Sets
López-Giráldez F, Moeller AH, Townsend JP. Evaluating Phylogenetic Informativeness as a Predictor of Phylogenetic Signal for Metazoan, Fungal, and Mammalian Phylogenomic Data Sets. BioMed Research International 2013, 2013: 621604. PMID: 23878813, PMCID: PMC3708382, DOI: 10.1155/2013/621604.Peer-Reviewed Original ResearchConceptsPhylogenomic data setsPhylogenetic informativenessPhylogenetic signalEffects of homoplasyPoor phylogenetic resolutionPhylogenetic resolutionSister cladeOutgroup taxaPhylogenetic researchTaxonomic groupsPhylogenetic inferenceAdvantageous genesGenesMetazoansCladeTaxaDiverse groupDiverse time scalesHomoplasyHaphazard samplingMammalsFungiOrganismsFungalMarkers
2012
Sex-specific gene expression during asexual development of Neurospora crassa
Wang Z, Kin K, López-Giráldez F, Johannesson H, Townsend JP. Sex-specific gene expression during asexual development of Neurospora crassa. Fungal Genetics And Biology 2012, 49: 533-543. PMID: 22626843, PMCID: PMC3397379, DOI: 10.1016/j.fgb.2012.05.004.Peer-Reviewed Original ResearchConceptsMating-type genesAsexual developmentMating typesNeurospora crassaGene expressionSex-specific gene expressionFungal life historyLight-responsive genesOverall gene expressionExpression levelsDifferent mating typesExpression of pheromonePheromone genesHigh expression levelsMat AType genesLife historyResponse genesExpression differencesDevelopment stagesGenesClonal developmentImpact of lightReceptor geneCrassaRBE controls microRNA164 expression to effect floral organogenesis
Huang T, López-Giráldez F, Townsend JP, Irish VF. RBE controls microRNA164 expression to effect floral organogenesis. Development 2012, 139: 2161-2169. PMID: 22573623, DOI: 10.1242/dev.075069.Peer-Reviewed Original ResearchConceptsCUP-SHAPED COTYLEDON1Zinc finger transcriptional repressorKey transcriptional regulatorMiR164 expressionPetal organogenesisArabidopsis flowersPetal developmentPlant developmentEffector genesTranscriptional regulatorsTranscriptional repressorFloral organogenesisGene productsDevelopmental eventsConcomitant regulationGenesOrgan boundariesOrganogenesisExpressionMiR164cCUC2RepressorBoundary specificationPromoterFlowers
2011
PhyDesign: an online application for profiling phylogenetic informativeness
López-Giráldez F, Townsend JP. PhyDesign: an online application for profiling phylogenetic informativeness. BMC Ecology And Evolution 2011, 11: 152. PMID: 21627831, PMCID: PMC3124428, DOI: 10.1186/1471-2148-11-152.Peer-Reviewed Original ResearchConceptsPhylogenetic informativenessPhylogenetic studiesPhylogenetic informativeness analysesBroad taxonomic samplingMolecular phylogenetic studiesTree of lifeOrthologous genesPhylogenetic samplingTaxonomic samplingPhylogenetic questionsPhylogenetic purposesEfficiency of sequencingSequence alignmentMarker selectionUltrametric treeDiverse suiteUtility of locusLociTreesUser-friendly toolGenomeGenesSequencingSpeciesDiversity
2009
The Ascomycota Tree of Life: A Phylum-wide Phylogeny Clarifies the Origin and Evolution of Fundamental Reproductive and Ecological Traits
Schoch CL, Sung GH, López-Giráldez F, Townsend JP, Miadlikowska J, Hofstetter V, Robbertse B, Matheny PB, Kauff F, Wang Z, Gueidan C, Andrie RM, Trippe K, Ciufetti LM, Wynns A, Fraker E, Hodkinson BP, Bonito G, Groenewald JZ, Arzanlou, de Hoog GS, Crous PW, Hewitt D, Pfister DH, Peterson K, Gryzenhout M, Wingfield MJ, Aptroot A, Suh SO, Blackwell M, Hillis DM, Griffith GW, Castlebury LA, Rossman AY, Lumbsch HT, Lücking R, Büdel B, Rauhut A, Diederich P, Ertz D, Geiser DM, Hosaka K, Inderbitzin P, Kohlmeyer J, Volkmann-Kohlmeyer B, Mostert L, O'Donnell K, Sipman H, Rogers JD, Shoemaker RA, Sugiyama J, Summerbell RC, Untereiner W, Johnston PR, Stenroos S, Zuccaro A, Dyer PS, Crittenden PD, Cole MS, Hansen K, Trappe JM, Yahr R, Lutzoni F, Spatafora JW. The Ascomycota Tree of Life: A Phylum-wide Phylogeny Clarifies the Origin and Evolution of Fundamental Reproductive and Ecological Traits. Systematic Biology 2009, 58: 224-239. PMID: 20525580, DOI: 10.1093/sysbio/syp020.Peer-Reviewed Original ResearchConceptsCharacter state reconstructionCommon ancestorAncestral character state reconstructionPhylogenetic informativeness analysesSexual reproductive structuresAscus dehiscenceMaximum likelihood phylogenyPhylogenetic informativenessEcological traitsFungal systematicsAncestral reconstructionNutritional modesRibosomal genesLargest phylumMorphological traitsRelated speciesReproductive structuresProtein geneAscomycota TreePezizomycotinaMultiple originsState reconstructionSporocarpsGene assessmentGenes
2008
The Phylogenetic Informativeness of Nucleotide and Amino Acid Sequences for Reconstructing the Vertebrate Tree
Townsend JP, López-Giráldez F, Friedman R. The Phylogenetic Informativeness of Nucleotide and Amino Acid Sequences for Reconstructing the Vertebrate Tree. Journal Of Molecular Evolution 2008, 67: 437-447. PMID: 18696029, DOI: 10.1007/s00239-008-9142-0.Peer-Reviewed Original ResearchConceptsAmino acid sequencePhylogenetic informativenessAcid sequenceVertebrate treeDNA sequencesMolecular evolutionary patternsEarly placental mammalsGenes c-mycDivergence timesMolecular evolutionPhylogenetic conflictEarly vertebratesEvolutionary patternsPlacental mammalsNucleotide sequenceMuroid rodentsFunctional constraintsGenesC-MycSupport valuesSequenceNucleotidesNumber of charactersHigh informativenessTrees