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BioMed Research International Functional Genomics, Genetics, and Bioinformatics Guest Editors: Youping Deng, Hongwei Wang, Ryuji Hamamoto, David Schaffer, and Shiwei Duan Functional Genomics, Genetics, and Bioinformatics BioMed Research International Functional Genomics, Genetics, and Bioinformatics GuestEditors:oupingDeng,HongweiWang,RyujiHamamoto, David Schaffer, and Shiwei Duan Copyright©2015HindawiPublishingCorporation.Allrightsreserved. Thisisaspecialissuepublishedin“BioMedResearchInternational.”AllarticlesareopenaccessarticlesdistributedundertheCreative CommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginal workisproperlycited. Contents FunctionalGenomics,Genetics,andBioinformatics,YoupingDeng,HongweiWang,RyujiHamamoto, DavidSchaffer,andShiweiDuan Volume2015,ArticleID184824,3pages EvolutionaryPatternandRegulationAnalysistoSupportWhyDiversityFunctionsExistedwithin PPARGeneFamilyMembers,TianyuZhou,XipingYan,GuosongWang,HeheLiu,XiangGan,TaoZhang, JiwenWang,andLiangLi Volume2015,ArticleID613910,11pages ThePlantGrowth-PromotingBacteriaAzospirillumamazonense:GenomicVersatilityand PhytohormonePathway,RicardoCecagno,TiagoEbertFritsch,andIreneSilveiraSchrank Volume2015,ArticleID898592,7pages ShapedSingularSpectrumAnalysisforQuantifyingGeneExpression,withApplicationtotheEarly DrosophilaEmbryo,AlexShlemov,NinaGolyandina,DavidHolloway,andAlexanderSpirov Volume2015,ArticleID689745,14pages EffectofCelastrolonGrowthInhibitionofProstateCancerCellsthroughtheRegulationofhERG ChannelInVitro,NanJi,JinjunLi,ZexiongWei,FanhuKong,HongyanJin,XiaoyaChen,YanLi, andYoupingDeng Volume2015,ArticleID308475,7pages TheExpressionandDistributionsofANP32AintheDevelopingBrain,ShanshanWang,YunliangWang, QingshanLu,XinshanLiu,FuyuWang,XiaodongMa,ChunpingCui,ChengheShi,JinfengLi, andDajinZhang Volume2015,ArticleID207347,8pages ProtectingIntestinalEpithelialCellNumber6againstFissionNeutronIrradiationthroughNF-𝜅B SignalingPathway,Gong-MinChang,Ya-BingGao,Shui-MingWang,Xin-PingXu,LiZhao,JingZhang, Jin-FengLi,Yun-LiangWang,andRui-YunPeng Volume2015,ArticleID124721,8pages HumanUmbilicalCordMesenchymalStemCellsInfectedwithAdenovirusExpressingHGFPromote RegenerationofDamagedNeuronCellsinaParkinson’sDiseaseModel,Xin-ShanLiu,Jin-FengLi, Shan-ShanWang,Yu-TongWang,Yu-ZhenZhang,Hong-LeiYin,ShuangGeng,Hui-CuiGong,BingHan, andYun-LiangWang Volume2014,ArticleID909657,7pages RelationshipbetweenCCRandNT-proBNPinChineseHFPatients,andTheirCorrelationswith SeverityofHF,ZhigangLu,BoWang,YunliangWang,XueqingQian,WeiZheng,andMengWei Volume2014,ArticleID106252,7pages CharacterizationofPutativecis-RegulatoryElementsinGenesPreferentiallyExpressedinArabidopsis MaleMeiocytes,JunhuaLi,JinhongYuan,andMingjunLi Volume2014,ArticleID708364,10pages AGenome-WideIdentificationofGenesUndergoingRecombinationandPositiveSelectionin Neisseria,DongYu,YuanJin,ZhiqiuYin,HongguangRen,WeiZhou,LongLiang,andJunjieYue Volume2014,ArticleID815672,9pages NovelApproachforCoexpressionAnalysisofE2F13andMYCTargetGenesinChronicMyelogenous Leukemia,FengfengWang,LawrenceW.C.Chan,WilliamC.S.Cho,PetrusTang,JunYu,Chi-RenShyu, NancyB.Y.Tsui,S.C.CesarWong,ParcoM.Siu,S.P.Yip,andBenjaminY.M.Yung Volume2014,ArticleID439840,7pages TheEffectsoftheContext-DependentCodonUsageBiasontheStructureofthensp1𝛼ofPorcine ReproductiveandRespiratorySyndromeVirus,Yao-zhongDing,Ya-nanYou,Dong-jieSun, Hao-taiChen,Yong-luWang,Hui-yunChang,LiPan,Yu-zhenFang,Zhong-wangZhang,PengZhou, Jian-liangLv,Xin-shengLiu,Jun-junShao,Fu-rongZhao,TongLin,LaszloStipkovits,ZygmuntPejsak, Yong-guangZhang,andJieZhang Volume2014,ArticleID765320,10pages CellType-DependentRNARecombinationFrequencyintheJapaneseEncephalitisVirus, Wei-WeiChiang,Ching-KaiChuang,MeiChao,andWei-JuneChen Volume2014,ArticleID471323,9pages ComputationalEvidenceofNAGNAGAlternativeSplicinginHumanLargeIntergenicNoncoding RNA,XiaoyongSun,SimonM.Lin,andXiaoyanYan Volume2014,ArticleID736798,7pages iCTX-Type:ASequence-BasedPredictorforIdentifyingtheTypesofConotoxinsinTargetingIon Channels,HuiDing,En-ZeDeng,Lu-FengYuan,LiLiu,HaoLin,WeiChen,andKuo-ChenChou Volume2014,ArticleID286419,10pages AnAssociationStudybetweenGeneticPolymorphismintheInterleukin-6ReceptorGeneand CoronaryHeartDisease,JiangqingZhou,XiaoliangChen,HuadanYe,PingPeng,YannaBa,XiYang, XiaoyanHuang,YaeLu,XinJiang,JiangfangLian,andShiweiDuan Volume2014,ArticleID504727,6pages Meta-AnalysisofLowDensityLipoproteinReceptor(LDLR)rs2228671PolymorphismandCoronary HeartDisease,HuadanYe,QianleiZhao,YiHuang,LingyanWang,HaiboLiu,ChunmingWang, DongjunDai,LeitingXu,MengYe,andShiweiDuan Volume2014,ArticleID564940,6pages UsingtheSadakaneCompressedSuffixTreetoSolvetheAll-PairsSuffix-PrefixProblem, MaanHajRachid,QutaibahMalluhi,andMohamedAbouelhoda Volume2014,ArticleID745298,11pages Associationbetween𝜀2/3/4,PromoterPolymorphism(−491A/T,−427T/C,and−219T/G)atthe ApolipoproteinEGene,andMentalRetardationinChildrenfromanIodineDeficiencyArea,China, JunLi,FuchangZhang,YunliangWang,YanWang,WeiQin,QingheXing,XueqingQian,TingweiGuo, XiaocaiGao,LinHe,andJianjunGao Volume2014,ArticleID236702,6pages Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 184824, 3 pages http://dx.doi.org/10.1155/2015/184824 Editorial Functional Genomics, Genetics, and Bioinformatics YoupingDeng,1HongweiWang,2RyujiHamamoto,2DavidSchaffer,3andShiweiDuan4 1DepartmentofInternalMedicine,RushUniversityCancerCenter,RushUniversityMedicalCenter,Chicago,IL60612,USA 2DepartmentofMedicine,UniversityofChicago,Chicago,IL60637,USA 3DepartmentofBioengineering,BinghamtonUniversity,Binghamton,NY13902,USA 4SchoolofMedicine,NingboUniversity,Ningbo,Zhejiang315211,China CorrespondenceshouldbeaddressedtoYoupingDeng;youping [email protected] Received10December2014;Accepted10December2014 Copyright©2015YoupingDengetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Biologyhasbecomethelandofthe“-omics,”includinggeno- Bioinformatics.Inthebioinformaticspapers,fourpapersdeal mics[1],transcriptomics[2,3],epigenomics[4],proteomics with transcriptomics data. F. Wang et al. developed a novel [5], lipidomics [6, 7], and metabolomics [8]. Each of these approachforcoexpressionanalysisofE2F1-3andMYCtarget “-omics”generatesahugeamountofhigh-throughputdata, genesinchronicmyelogenousleukemia(CML);theyfound anditisachallengebothtoanalyzethesedataandtofurther asignificantdifferenceinthecoexpressionpatternsofthose investigatethefunctionofspecificmolecules.Thoughmore candidate target genes between the normal and the CML genomeshavebeencompletedduetotherapiddevelopment groups. It is challenging to analyze the quantity of image ofsequencingtechnology[9],wecannotunderstandtheinfo- data on gene expression. A. Shlemov et al. developed a rmation contained within a genome until we mine out its method called 2D singular spectrum analysis (2D-SSA) for implicated functions including downstream transcription, applicationto2Dand3Ddatasetsofembryoimagesrelated translation,epigeneticsmodulation,andmetabolicpathways. to gene expression; it turned out to work pretty well. J. Li Inthisspecialissue,wemainlyfocusonfunctional“-omics” et al. characterized putative cis-regulatory elements (CREs) andbioinformatics. associatedwithmalemeiocyte-expressedgenesusinginsilico The Peer-reviewed papers are collected in the special tools.Theyfoundthattheupstreamregions(1kb)ofthetop issue.Theyareapproximatelydividedintothreeareas:bioin- 50 genes preferentially expressed in Arabidopsis meiocytes formatics,functionalgenomics,andfunctionalgenetics.The possessed conserved motifs, which were potential binding majority of the papers are purely bioinformatics related sites of transcription factors. NAGNAG alternative splicing papers.Wedefinebioinformaticspapersasthoseusingcom- playsanimportantroleinbiologicalprocessesandrepresents putationaltoolsordevelopingmethodstoanalyzefunctional ahighlyadaptablesystemforposttranslationalregulationof “-omics”datawithoutusingwetlabs.Twopapersfellintothe genefunction.Interestingly,X.Sunetal.identifiedabout31 categoryoffunctionalgen-omics,whichisfocusedonusing NAGNAG alternative splicing sites that were identified in whole genome level wet-lab technology to find important humanlargeintergenicnoncodingRNAs(lincRNAs). molecules and investigate their potential functions. Five Threepapersarefocusedonthedeificationofnewgene papers are considered as functional genetics papers. Func- family members and gene evolution. Conotoxins are small tionalgeneticsisabroadconcepthereandthesepapersare disulfide-rich neurotoxic peptides, which can bind to ion concentratedonstudyingthemolecularfunctionsandmech- channelswithveryhighspecificityandregulatetheiractiv- anisms of individual molecules using wet-lab experimental ities.H.Dingetal.developedanovelmethodcallediCTX- approaches. Type,whichisasequence-basedpredictorthatcanbeusedto 2 BioMedResearchInternational identifythetypesofconotoxinsintargetingionchannels.A couldpromotetheregenerationofdamagedParkinson’sdis- user-friendlywebtoolisalsoavailable.Y.-Z.Zhouetal.ana- ease(PD)cellsathigherefficacythanthesupernatantfrom lyzed the evolution pattern and function diversity of PPAR hUC-MSCsalone.Thus,thecombinationofhUC-MSCwith gene family members based on 63 homology sequences of HGF could potentially be a new biological treatment for PPARgenesfrom31species.Theyfoundthatgeneduplication PD. One paper is focused on cancer. N. Ji et al. found that events,selectionpressuresonHOLIdomain,andthevariants celastrolhadantiprostatecancereffectspartiallythroughthe 󸀠 on promoter and 3UTR are critical for PPARs evolution downregulation of the expression level of hERG channel in and acquiring diversity functions. There has recently been DU145cells,suggestingthatcelastrolmaybeapotentialagent considerable focus on its two human pathogenic species N. against prostate cancer with a mechanism of blocking the meningitidisandN.gonorrhoeae,whichbelongtoNeisseria,a hERG channel. One paper is studying heart disease. Z. Lu genusofgram-negativebacteria.D.Yuetal.selected18Neis- etal.reportedthatthelevelsofNT-proBNPandCCRwere seria genomes, preformed a comparative genome analysis, closelyrelatedtotheoccurrenceofHFandwereindependent and identified 635 genes with recombination signals and 10 risk factors for heart failure (HF). Meanwhile, there was a genesthatshowedsignificantevidenceofpositiveselection. significant negative correlation between the levels of NT- Furtherfunctionalanalysesrevealedthatnofunctionalbias proBNPandCCR.Oneinterestingpaperistryingtounder- was found in the recombined genes. The data help us to standthefunctionofJapaneseencephalitisvirus(JEV),and understandtheadaptiveevolutioninNeisseria. they have demonstrated that RNA recombination in JEV One paper tried to solve the key algorithm issue called occurs unequally in different cell types. They conclude that theall-pairssuffix-prefixmatchingproblem,whichiscrucial theadjustmentofviralRNAtoanappropriatelylowerlevelin fordenovogenomeassembly.M.H.Rachidetal.developed mosquitocellspreventsovergrowthofthevirusandisbenefi- a space-economical solution to the problem using the gen- cialforcellstosurvivetheinfection. eralized Sadakane compressed suffix tree. One paper con- Insummary,thisspecialissuepresentsabroadrangeof ducted a comparative genomics analysis. R. Cecagno et al. topicsfromfunctionalgenomics,genetics,andbioinformat- found that the versatile gene repertoire in the genome of ics.Itcoversavarietyofdiseasessuchascancer,heart,and rhizospherebacteriumAzospirillumamazonensecouldhave neuralandinfectiousdiseases.Thestudyorganismsinclude beenacquiredfromdistantlyrelatedbacteriafromhorizontal human,mouse,plant,andmicroorganisms.Wehopethatthe transfer. They also demonstrated that the coding sequence readers will find interesting knowledge and methods in the related to production of phytohormones, such as flavin issue. monooxygenaseandaldehydeoxidase,islikelytorepresent thetryptophan-dependentTAMpathwayforauxinproduc- YoupingDeng tion in this bacterium. They conclude that the genomic HongweiWang structureofthebacteriahasevolvedtomeettherequirement RyujiHamamoto for adaptation to the rhizosphere and interaction with host DavidSchaffer plants. ShiweiDuan Onearticleconductedameta-analysis.H.Yeetal.have demonstratedthatrs2228671isaprotectivefactorofCHDin References Europeans.Onepaperisconcentratedonthemicroorganism bioinformatics.Y.Dingetal.recognizedtherolesofthesyn- onymouscodonusageintheformationofnsp1𝛼structureof [1] M. Jia, Y. Liu, Z. Shen et al., “HDAM: a resource of human diseaseassociatedmutationsfromnextgenerationsequencing porcinereproductiveandrespiratorysyndromevirusPRRSV. studies,”BMCMedicalGenomics,vol.6,supplement1,article S16,2013. Functional Genomics. There are two papers that conducted [2] Y.Deng,S.A.Meyer,X.Guanetal.,“Analysisofcommonand geneassociationstudiesbasedongenomewidedata.J.Liet al.foundthatthepresenceofATT𝜀4haplotypewasassociated specificmechanismsofliverfunctionaffectedbynitrotoluene compounds,”PLoSONE,vol.6,no.2,ArticleIDe14662,2011. withanincreasedriskofmentalretardation(MR)inchildren but did not find any significant association between single [3] H.Jiang,Y.Deng,H.-S.Chenetal.,“Jointanalysisoftwomicr- loci of the four common ApoE polymorphisms (−491A/T, oarraygene-expressiondatasetstoselectlungadenocarcinoma −427T/C,−219T/G,and𝜀2/3/4)andMRorborderlineMR. markergenes,”BMCBioinformatics,vol.5,article81,2004. J.Zhouetal.didnotfindanassociationbetweenrs7529229 [4] J.Melson,Y.Li,E.Cassinottietal.,“Commonalityanddiffer- andchronicheartdisease(CHD)inHanChinese.However, encesofmethylationsignaturesintheplasmaofpatientswith theirmeta-analysesindicatedthatrs7529229wasassociated pancreaticcancerandcolorectalcancer,”InternationalJournal withtheCHDriskinEuropeans. ofCancer,vol.134,no.11,pp.2656–2662,2014. [5] F.Xu,G.Li,C.Zhaoetal.,“Globalproteininteractomeexplo- Functional Genetics. There are 5 articles that investigate the rationthroughmininggenome-scaledatainArabidopsistha- individual gene function in different areas. Two papers are liana,”BMCGenomics,vol.11,articleS2,supplement2,2010. related to neural diseases. G.-M. Chang et al. found that [6] Y. Wang, C. Zhao, J. Mao et al., “Integrated lipidomics and activating NF-𝜅B signaling pathway can protect intestinal transcriptomicanalysisofperipheralbloodrevealssignificantly epithelialcellNo.6againstfissionneutronirradiation.X.-S. enrichedpathwaysintype2diabetesmellitus,”BMCMedical Liuetal.demonstratedthathepatocytegrowthfactor(HGF) Genomics,vol.6,no.1,articleS12,2013. BioMedResearchInternational 3 [7] X. Zhou, J. Mao, J. Ai et al., “Identification of plasma lipid biomarkersforprostatecancerbylipidomicsandbioinformat- ics,”PLoSONE,vol.7,no.11,ArticleIDe48889,2012. [8] T.W.-M.Fan,A.N.Lane,andR.M.Higashi,“Thepromiseof metabolomicsincancermoleculartherapeutics,”CurrentOpin- ioninMolecularTherapeutics,vol.6,no.6,pp.584–592,2004. [9] F.Wang,L.Lu,C.Yuetal.,“DevelopmentofanovelDNAsequ- encingmethodnotonlyforhepatitisBvirusgenotypingbutalso fordrugresistantmutationdetection,”BMCMedicalGenomics, vol.6,no.1,articleS15,2013. Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 613910, 11 pages http://dx.doi.org/10.1155/2015/613910 Research Article Evolutionary Pattern and Regulation Analysis to Support Why Diversity Functions Existed within PPAR Gene Family Members TianyuZhou,1XipingYan,1GuosongWang,1HeheLiu,1,2XiangGan,1 TaoZhang,1JiwenWang,1andLiangLi1 1KeyLabofSichuanProvince,InstituteofAnimalGeneticsandBreeding,SichuanAgriculturalUniversity, Ya’an,Sichuan625014,China 2CollegeofAnimalScienceandTechnology,SichuanAgriculturalUniversity,Ya’an,Sichuan625014,China CorrespondenceshouldbeaddressedtoHeheLiu;[email protected] Received30June2014;Accepted4November2014 AcademicEditor:RyujiHamamoto Copyright©2015TianyuZhouetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Peroxisomeproliferators-activatedreceptor(PPAR)genefamilymembersexhibitdistinctpatternsofdistributionintissuesand differinfunctions.ThepurposeofthisstudyistoinvestigatetheevolutionaryimpactsondiversityfunctionsofPPARmembersand theregulatorydifferencesongeneexpressionpatterns.63homologysequencesofPPARgenesfrom31specieswerecollectedand analyzed.TheresultsshowedthatthreeisolatedtypesofPPARgenefamilymayemergefromtwicetimesofgeneduplicationevents. TheconserveddomainsofHOLI(ligandbindingdomainofhormonereceptors)domainandZnF C4(C4zincfingerinnuclearin hormonereceptors)areessentialforkeepingbasicrolesofPPARgenefamily,andthevariantdomainsofLCRsmayberesponsible fortheirdivergenceinfunctions.ThepositiveselectionsitesinHOLIdomainarebenefitforPPARstoevolvetowardsdiversity 󸀠 functions.Theevolutionaryvariantsinthepromoterregionsand3 UTRregionsofPPARsresultintodifferentialtranscription factorsandmiRNAsinvolvedinregulatingPPARmembers,whichmayeventuallyaffecttheirexpressionsandtissuesdistributions. 󸀠 Theseresultsindicatethatgeneduplicationevent,selectionpressureonHOLIdomain,andthevariantsonpromoterand3 UTR areessentialforPPARsevolutionanddiversityfunctionsacquired. 1.Introduction (DNA-bindingdomain),LBD(ligand-bindingdomain),AF1 (activation function 1), AF2 (activation function 2), and a Peroxisomeproliferators-activatedreceptors(PPARs)aretra- variablehingeregion.TheDBDandLBDconsistofahighly nscription factors belonging to the ligand-activated nuclear conserved DNA-binding domain and a moderately con- receptorsuperfamily,whichplaykeyrolesinregulatingmeta- servedligand-bindingdomain,respectively.TheAF1andAF2 bolism,inflammation,andimmunity.Invertebrates,thegene aretwoligand-independentactivationfunctiondomains.All family of PPAR consisted of PPAR𝛼, PPAR𝛽 (also called these regions except the variable hinge region are highly PPARb/d or PPAR𝛿), and PPAR𝛾 [1]. Recently, a consid- conserved among PPAR members and are responsible for erable number of papers have reviewed their importance keepingtheirfunctions[3].AlthoughthePPARssharehigh in functions within various physiological and biochemistry similaritieswitheachotherinstructures,theyexhibitdistinct processes[2–5].Theirspecialeffectsandfunctionalmanners patternsofdistributionintissuesanddifferinfunctions[7]. ofdependingonaligand-activatedwayevenhaveattracted It has been summarized that PPAR𝛼 mainly is involved in somescientiststoconsiderthemasadrugtargetfortherapy theoxidationprocessofhepatocytes,PPAR𝛽mainlytargets ofsomemetabolicdisorders,suchasthetype2diabetesmel- withintheadipocyteproliferation,andPPAR𝛾playsessential litusandatherosclerosis[6]. rolesinoriginationandfatedeterminationofpreadipocyte. IthasbeenwellestablishedthatthePPARscanbedivided In adult rat, it has shown that PPARs had different expres- into five distinct functional regions, which include DBD sion patterns [8]. Definitely, PPAR𝛼 is highly expressed in

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