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Comparative Genomics: International Workshop, RECOMB-CG 2009, Budapest, Hungary, September 27-29, 2009. Proceedings PDF

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Lecture Notes in Bioinformatics 5817 EditedbyS.Istrail,P.Pevzner,andM.Waterman EditorialBoard: A.Apostolico S.Brunak M.Gelfand T.Lengauer S.Miyano G.Myers M.-F.Sagot D.Sankoff R.Shamir T.Speed M.Vingron W.Wong Subseries of Lecture Notes in Computer Science Francesca D. Ciccarelli István Miklós (Eds.) Comparative Genomics International Workshop, RECOMB-CG 2009 Budapest, Hungary, September 27-29, 2009 Proceedings 1 3 SeriesEditors SorinIstrail,BrownUniversity,Providence,RI,USA PavelPevzner,UniversityofCalifornia,SanDiego,CA,USA MichaelWaterman,UniversityofSouthernCalifornia,LosAngeles,CA,USA VolumeEditors FrancescaD.Ciccarelli EuropeanInstituteofOncology IFOM-IEOCampus,ViaAdamello,16,20139Milan,Italy E-mail:[email protected] IstvánMiklós HungarianAcademyofSciences RényiInstitute Reáltanodautca13-15,1053Budapest,Hungary E-mail:[email protected] LibraryofCongressControlNumber:2009936053 CRSubjectClassification(1998):F.2,G.3,E.1,H.2.8,J.3 LNCSSublibrary:SL8–Bioinformatics ISSN 0302-9743 ISBN-10 3-642-04743-2SpringerBerlinHeidelbergNewYork ISBN-13 978-3-642-04743-5SpringerBerlinHeidelbergNewYork Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeorpartofthematerialis concerned,specificallytherightsoftranslation,reprinting,re-useofillustrations,recitation,broadcasting, reproductiononmicrofilmsorinanyotherway,andstorageindatabanks.Duplicationofthispublication orpartsthereofispermittedonlyundertheprovisionsoftheGermanCopyrightLawofSeptember9,1965, initscurrentversion,andpermissionforusemustalwaysbeobtainedfromSpringer.Violationsareliable toprosecutionundertheGermanCopyrightLaw. springer.com ©Springer-VerlagBerlinHeidelberg2009 PrintedinGermany Typesetting:Camera-readybyauthor,dataconversionbyScientificPublishingServices,Chennai,India Printedonacid-freepaper SPIN:12769131 06/3180 543210 Preface Asgenome-sequencingcostscontinuetheirdownwardspiral,sequencingofclosely related organisms has become increasingly affordable. The growing amount of genomicdata availabledemands for the constantdevelopmentof computational toolstobeappliedincomparativegenomics.TheRECOMBWorkshoponCom- parative Genomics (RECOMB-CG) is devoted to bringing together scientists workingonallaspectsofcomparativegenomics,fromcomputerscientists,math- ematicians and statisticians working on novel computational approaches for genome analysis and comparison, to biologists applying these computational tools to study the structure and the evolution of prokaryotic and eukaryotic genomes. Thisvolumecontainsthe19paperspresentedatthe7thAnnualRECOMB-CG workshopheldduringSeptember27–29,2009attheRenyiInstitute,inBudapest, Hungary. The papers published in these proceedings were selected for oral pre- sentationfrom31submissionsfromscientistsaroundthe world.Eachpaperwas reviewedbyatleastthreemembersoftheProgramCommitteeinastringentand thoughtfulpeer-reviewprocess. The conference itself was enlivened by invited keynote presentations from Richard Durbin (Welcome Trust Sanger Institute), Jotun Hein (Department of Statistics, University of Oxford, UK), Laurence Hurst (Department of Biol- ogy and Biochemistry, University of Bath, UK), Csaba Pa´l (Evolutionary Sys- temsBiologyGroup,BiologicalResearchCenter,Szeged,Hungary),LisaStubbs (School of Molecular and Cellular Biology, University of Illinois at Urbana- Champaign) and Jeroen Raes (EMBL Heidelberg). These talks were supple- mented by both the presentations of the papers in this volume and a poster session. Together, talks and papers highlighted the state-of-the-art of compar- ative genomics tools and applications. From the inference of evolution in ge- neticregulatorynetworks,tothedivergentfatesofgeneandgenomeduplication events, to the importance of new computational approaches to unraveling the structuralevolutionof genomes,these presentationsillustrate the crucialrole of comparative genomics in understanding genome function. RECOMB-CG 2009 would not have been possible without the participation of the many scientists who contributed their time and effort to making the con- ference a success. We thank the scientists who submitted their work for presen- tation at the conference, those members of the Program Committee who made everyefforttoensurefairandbalancedreviewofthemanypaperssubmittedfor consideration,the members of the localOrganizingCommittee for arrangingall themyriaddetailsoftheorganizationalaspectsoftheevent,andthemembersof the Steering Committee for their ongoing dedication and guidance. RECOMB- CG 2009 is also deeply indebted to its sponsors including the National Office VI Preface for Research and Technology, the Hungarian Academy of Sciences, the Renyi Institute and the Hungarian Society for Bioinformatics. It is the continued support and dedication of this community that allows RECOMB-CG to bring together comparative genomics researchers from across the globe to exchange ideas and information and focus the force of comparative genomics on improving our understanding of genome evolution and function. August 2009 Francesca Ciccarelli Istvan Mikl´os Table of Contents Yeast Ancestral Genome Reconstructions: The Possibilities of Computational Methods .......................................... 1 Eric Tannier Natural Parameter Values for Generalized Gene Adjacency............ 13 Zhenyu Yang and David Sankoff Parking Functions, Labeled Trees and DCJ Sorting Scenarios.......... 24 A¨ıda Ouangraoua and Anne Bergeron Counting All DCJ Sorting Scenarios................................ 36 Mar´ılia D.V. Braga and Jens Stoye Minimal Conflicting Sets for the Consecutive Ones Property in Ancestral Genome Reconstruction.................................. 48 Cedric Chauve, Utz-Uwe Haus, Tamon Stephen, and Vivija P. You Finding Nested Common Intervals Efficiently ........................ 59 Guillaume Blin and Jens Stoye DCJ Median Problems on Linear Multichromosomal Genomes: Graph Representation and Fast Exact Solutions............................ 70 Andrew Wei Xu RearrangementModels and Single-Cut Operations ................... 84 Paul Medvedev and Jens Stoye Aligning Two Genomic Sequences That Contain Duplications.......... 98 Minmei Hou, Cathy Riemer, Piotr Berman, Ross C. Hardison, and Webb Miller Inferring the Recent Duplication History of a Gene Cluster............ 111 Giltae Song, Louxin Zhang, Toma´ˇs Vinaˇr, and Webb Miller Pseudo Boolean Programming for Partially Ordered Genomes ......... 126 S´ebastien Angibaud, Guillaume Fertin, Annelyse Th´evenin, and St´ephane Vialette Computing the Summed Adjacency Disruption Number between Two Genomes with Duplicate Genes Using Pseudo-BooleanOptimization.... 138 Jo˜ao Delgado, Inˆes Lynce, and Vasco Manquinho Reconstructing Histories of Complex Gene Clusters on a Phylogeny .... 150 Toma´ˇs Vinaˇr, Bronˇa Brejova´, Giltae Song, and Adam Siepel VIII Table of Contents Co-evolutionary Models for Reconstructing Ancestral Genomic Sequences: Computational Issues and Biological Examples ............ 164 Tamir Tuller, Hadas Birin, Martin Kupiec, and Eytan Ruppin Whole-Genome Analysis of Gene Conversion Events.................. 181 Chih-Hao Hsu, Yu Zhang, Ross Hardison, and Webb Miller A Statistically Fair Comparison of Ancestral Genome Reconstructions, Based on Breakpoint and RearrangementDistances .................. 193 Zaky Adam and David Sankoff Comparative Genomics and Extensive Recombinations in Phage Communities .................................................... 205 Guylaine Poisson, Mahdi Belcaid, and Anne Bergeron Properties of Sequence Conservation in Upstream Regulatory and Protein Coding Sequences among Paralogs in Arabidopsis thaliana ..... 217 Dale N. Richardson and Thomas Wiehe Transcription Factor Binding Probabilities in Orthologous Promoters: An Alignment-Free Approachto the Inference ofFunctional Regulatory Targets ......................................................... 229 Xiao Liu and Neil D. Clarke Author Index.................................................. 241 Yeast Ancestral Genome Reconstructions: The Possibilities of Computational Methods Eric Tannier INRIARhˆone-Alpes, Universit´edeLyon, F-69000, Universit´e Lyon 1, CNRS,UMR 5558, Laboratoire deBiom´etrie et Biologie E´volutive, F-69622, Villeurbanne, France Abstract. In 2006, a debate has risen on the question of theefficiency ofbioinformaticsmethodstoreconstructmammalianancestralgenomes. Threeyearslater,Gordonetal.(PLoSGenetics,5(5),2009)chosenotto useautomaticmethodstobuildupthegenomeofa100million yearold Saccharomyces cerevisiae ancestor. Their manually constructed ances- tor provides a reference genome to test whether automatic methods are indeed unable to approach confident reconstructions. Adapting several methodological frameworks to thesame yeast gene order data, I discuss the possibilities, differences and similarities of the available algorithms forancestralgenomereconstructions.Themethodscanbeclassifiedinto two types: local and global. Studying the properties of both helps to clarifywhatwecanexpectfromtheirusage.Bothmethodsproposecon- tiguous ancestral regions that come very close (> 95% identity) to the manually predicted ancestral yeast chromosomes, with a good coverage of theextant genomes. 1 Introduction The reconstruction of ancestral karyotypes and gene orders from homologies between extant species is a long-standing problem [7]. It helps to understand the large-scale evolutionary mutations that differentiate the present genomes. Computational methods to handle gene order and propose ancestral genome architectures have a shorter [17], but prolific [8] history. However, despite the numerous efforts of the computational biology community, two recent rounds of publications have put a doubt on their efficiency. In 2006, comparing ances- tralboreoeutheriangenomereconstructionsmade bycytogeneticistsonone side and bioinformaticians on the other, Froenicke et al. [9] found that the man- ually constructed and expertized cytogenetics one was not acceptably recov- ered by computational biology. This provoked many comments [2,15] published the same year. Since then, several bioinformatics teams have tried to approach the manually obtained boreoeutherian ancestor [13,4,1]. In may 2009, Gordon et al. [10] published the refined configuration of the genome of an ancestor of Saccharomyces cerevisiae (whichis approximatelyas ancientas the boreoeuthe- rianancestor),andchosenottouseanycomputationalframework,arguingthat thosearestillindevelopmentandyetcannothandletheavailabledata.Itseems tohavebeenconfirmedbythepublication,afewweekslater,bytheGenolevures F.D.CiccarelliandI.Mikl´os(Eds.):RECOMB-CG2009,LNBI5817,pp.1–12,2009. (cid:2)c Springer-VerlagBerlinHeidelberg2009 2 E. Tannier consortium [18], of a wide yeast genome comparative study including a recon- structionofanancestralconfigurationofsomenonduplicatedspecies,withayet unpublished method [11]. Thus the ancestor of duplicated species constructed by Gordon et al. [10] is still inaccessible by this approach. Sankoff [16] even- tually wrote a comment detailing the deficiencies of computational approaches, yet with an optimistic conclusion for the future. But right now there still seems to be a gap between formal methods and the application they are made for. This paper intends to fill this gap, and presents efficient implementations of automatic methods on yeast genomes. In [4], a new computational framework to reconstruct ancestral genomes was presented, generalizing a method by Ma et al. [13]. Whereas the earlier meth- odswereallbasedonadistanceminimizationprinciplethatisneverusedinthe manualreconstructions,these onestendtomimic the principlesusedbycytoge- neticists on mammalian data, which appear to be very close the the ones used by Gordon et al. [10] on yeast genomic data. This framework can handle the presence of a whole genome duplication in the history of the available species, as it was already remarkedin [14], a study using teleost fish genomes. It was shown in [4] that implementing this method on mammalian genomes resulted in a boreoeutherian ancestor which is very close to the one proposed by cytogeneticists. It shows in particular more similarity than the results of the distance based methods. Here I applied two different frameworks (the one describedin[4]andthedistancebased“GuidedGenomeHalving”ofZhengetal. [20])onthesameyeastdatausedbyGordonetal. [10]andcomparedtheresults with the manually constructed ancestral configuration. I used genomic markers that cover a large part of the extant genomes, and which allow to apply both methodsonthe sameinstance.Analyzingthedifferencesbetweenthe three(one manually and two computationally) constructed ancestors helps to understand the behavior of automatic methods and show what can be expected from them at the present time. 2 The Two Kinds of Methods In this section, I describe the concepts of the two kinds of methods, and why they often give different results. These reasons, to my mind, are an important part of the terms of the debates that have sometimes opposed biologists and bioinformaticians[9,2,15]. More details on the local method canbe found in [4], and on global methods in [8]. 2.1 The Local Method The local method consists in three steps: – identifying ancestral markers and their homologs in extant genomes; – searching for ancestral syntenies, i.e. sets of ancestral markers that are be- lieved to be contiguous in the ancestral genome, and weighting these an- cestral syntenies according to the confidence put in their presence in the ancestral genome, guided by its phylogenetic signal;

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