Table Of Content

Springer Handbook oƒ Bio-/Neuro- Informatics Kasabov Editor 123 Springer Handbook of Bio-/Neuroinformatics SpringerHandbookprovides aconcisecompilationofapproved key information on methods of research, general principles, and functionalrelationshipsinphysical andappliedsciences.Theworld’s leading experts in the fields of physicsandengineeringwillbeas- signedbyoneorseveralrenowned editorstowritethechapterscom- prising each volume. The content is selected by these experts from Springersources(books,journals, onlinecontent)andothersystematic andapprovedrecentpublicationsof scientificandtechnicalinformation. Thevolumesaredesignedtobe useful as readable desk reference booktogiveafastandcomprehen- siveoverviewandeasyretrievalof essentialreliablekeyinformation, includingtables,graphs,andbibli- ographies.Referencestoextensive sourcesareprovided. Springer Handbook of Bio-/Neuroinformatics Nikola Kasabov (Ed.) With490Figuresand92Tables 123 Editor NikolaKasabov AucklandUniversityofTechnology KEDRI–KnowledgeEngineeringandDiscoveryResearchInstitute 120MayoralDrive Auckland,NewZealand ISBN:978-3-642-30573-3 e-ISBN:978-3-642-30574-0 DOI10.1007/978-3-642-30574-0 SpringerDordrechtHeidelbergLondonNewYork LibraryofCongressControlNumber: 2013951342 (cid:2)c Springer-VerlagBerlinHeidelberg2014 Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewhole orpartofthematerialisconcerned,specificallytherightsoftranslation, reprinting,reuseofillustrations,recitation,broadcasting,reproductionon microfilmorinanyotherway,andstorageindatabanks.Duplicationofthis publicationorpartsthereofispermittedonlyundertheprovisionsofthe GermanCopyrightLawofSeptember9,1965,initscurrentversion,and permissionforusemustalwaysbeobtainedfromSpringer.Violationsare liabletoprosecutionundertheGermanCopyrightLaw. Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.in thispublicationdoesnotimply,evenintheabsenceofaspecificstatement, thatsuchnamesareexemptfromtherelevantprotectivelawsandregulations andthereforefreeforgeneraluse. Productionandtypesetting:le-texpublishingservicesGmbH,Leipzig SeniorManagerSpringerHandbook:Dr.W.Skolaut,Heidelberg Typographyandlayout:schreiberVIS,Seeheim Illustrations:HippmannGbR,Schwarzenbruck Coverdesign:eStudioCalamarSteinen,Barcelona Coverproduction:WMXDesignGmbH,Heidelberg Printingandbinding:StürtzGmbH,Würzburg Printedonacidfreepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) 89/3180/YL 543210 V FormymotherKapkaNikolovaMankova-Kassabova(1920–2012) whowroteinBulgarian,amongmanyothers,thelittlepoems: Iwillrunoutoftime (cid:0)(cid:2)(cid:3)(cid:2)(cid:4)(cid:5)(cid:6)(cid:7)(cid:5)(cid:8)(cid:9)(cid:10)(cid:7)(cid:11)(cid:9)(cid:5)(cid:7)(cid:2) Tounlockallthesecrets, (cid:12)(cid:10)(cid:13)(cid:10)(cid:14)(cid:8)(cid:10)(cid:11)(cid:10)(cid:15)(cid:7)(cid:10)(cid:16)(cid:9)(cid:5)(cid:7)(cid:2)(cid:9)(cid:10)(cid:17)(cid:5)(cid:7)(cid:5)(cid:2)(cid:7)(cid:18) Tohealallthewounds, (cid:12)(cid:10)(cid:5)(cid:14)(cid:19)(cid:2)(cid:20)(cid:21)(cid:22)(cid:10)(cid:4)(cid:23)(cid:18)(cid:22)(cid:2)(cid:24)(cid:20)(cid:5)(cid:7)(cid:2)(cid:13)(cid:10)(cid:9)(cid:5) Toexpressallmylove. (cid:25)(cid:11)(cid:10)(cid:5)(cid:14)(cid:20)(cid:10)(cid:26)(cid:10)(cid:19)(cid:27)(cid:17)(cid:18)(cid:22)(cid:7)(cid:10)(cid:6)(cid:5) FromtheeditorofthisSpringerHandbook,NikolaKasabov VII Foreword Life is a striking state of material that emerged 3.6billion years ago on our earth. It has the ability of self-reproduction, by keeping information about itself in itself. The marriage of information and matter makes it possible to implement the evolu- tionalmechanism.Thus,lifehasdevelopedtoachieveavarietyofamazingstructures and functions. In particular, we humans have appeared, with the characteristics of intelligenceandconsciousness,constructingsocietiesandculture. Now the time is ripe to understand the mechanisms of living systems, where in- formationiskeptandprocessedefficientlyandrobustly.Thesemechanismsarehighly complex and exquisite; their structures range from the molecular level to the higher level of the brain function. Advanced information science/technology is required to deciphertheinformationmechanismsoflife.Thisresearchfieldiscomposedofbioin- formaticsandneuroinformatics,whicharecloselyrelated.Theyincludeawiderange of hierarchical levels of molecules, cells, systems, and individuals. We need a good Shun-ichiAmari perspectiveoftheseextremelywidefieldsinasystematicandunderstandableway. ThepresentHandbookisintendedtoprovidenotonlyanoverviewofthestateof theartinbioinformaticsandneuroinformaticsandtherelatedresearchproblems,but also detailed informatics methods and techniques to address them. In this Handbook onecaneasilyfindimportanttheoreticalinformaticstoolsnecessaryforbioinformatics andneuroinformaticsresearch,includingthenecessarydetails. Iamhighlypleasedtoseethatsuchahandbook,coveringallaspectsofbioinfor- maticsandneuroinformaticstogetherwiththeirtoolsandmethods,isbeingpublished. BrainScienceInstitute RIKEN,Saitama Shun-ichiAmari Professor Shun-ichi Amari is IEEE Life Fellow, foreign member of the Polish Academy of Science and Professor-Emeritus at the University of Tokyo. He is past- Director of he RIKEN Brain Science Institute and is now a senior advisor. He has publishedmorethan300papers,includinginitiationofinformationgeometryandpi- oneering works on neural networks. He is the past President of International Neural NetworksSociety(INNS),theInstituteofElectronic,InformationandCommunication Engineers, Japan (IEICE) and founding President of Asian-Pacific Neural Networks Assembly(APNNA).Heisafoundingco-editor-in-chiefofNeuralNetworks.Here- ceived the Emanuel A. Piore Award and Neural Networks Pioneer Award from the IEEE,theJapanAcademyAward,theJapaneseOrderofCulturalMerit,andtheINNS GaborAward,amongmanyothers. IX Foreword FromDatatoSynthesis:TheHumanBrainProject anaccelerateddevelopmentofbrain inspired computing technologies. Brain research is entering its maturing stage. Enor- Those technologies will be based mous amounts of data, information, and knowledge on the knowledge generated from havebeenaccumulatedandarebeingaccumulatedev- the new insights of brain struc- ery day. The challenge now is to put all these into ture and function obtained in the integrated models and systems and to facilitate a bet- HBP. Specifically, the HBP will terunderstandingofthebrain.ThisSpringerHandbook develop a high performance, visu- ofBio-/Neuroinformaticsisverytimelyinthisrespect. allyinteractiveexa-scalecomputing The European Commission has recently approved infrastructure,novellowpower,ro- the Human Brain Project (HBP) as a flagship in bust, self-adapting computing, and the Future Emerging Technologies (FET) program communication devices and with (www.humanbrainproject.eu). The HBP commenced this lay the groundwork for a new Foto:F.Hentschel a30monthsramp-upphasein2013andisexpectedto fundamentallydifferentparadigmof KarlheinzMeier continueforatotalof10years.Theoverallgoalofthe computing. UniversitätHeidelberg projectistobuildanewEuropeanresearchinfrastruc- In order to achieve these goals, Kirchhoff-Institut tureforbrainrelatedresearchwithastrongemphasison the HBP has started to build six fürPhysik Co-Directorofthe state-of-the-art information and communication tech- technology platforms, which will HumanBrainProject nologies (ICT). Through the development of methods serve the scientific community in and tools, the integration of data, and the construction Europe and beyond in addressing the goals described of technology platforms the HBP will follow the suc- above. The six platforms will be hosted by partner cessfulmodeloflarge-scaleresearchinfrastructuresin groups of the HBP and dedicate their work to the fol- other scientific fields to tackle one of the most funda- lowingtasks: mentalchallengesofbasicresearch,linkingtheresults directlytomedicalandcomputingapplications. 1. Neuroinformaticsplatform:Thetaskistoaggregate TheHBPaddressesthreemajorresearchareas:neu- neurosciencedataandtodeliverbrainatlases. roscience, neuromedicine, and future computing. In 2. Medical informatics platform: the task is to ag- neuroscience the project aims at an accelerated under- gregate clinical records and to classify brain dis- standingofthehumanbrainbybuildingandsimulating eases. unifyingbrainmodels.Progressinthischallengingarea 3. Brain simulation platform: the task is to develop of basic research is expected by increasing the value software tools and to run closed loop brain simu- ofpastandfutureexperimentsthroughintegrationinto lations. publiclyavailablebrainatlases;fillingopenknowledge 4. High performance computing platform: the task is gaps using predictive software tools and strategically todevelopandoperateHPCsystemsoptimizedfor selectedexperiments,whichwillbeprioritizedandop- brainsimulations. timized for the use in simulations. In neuromedicine 5. Neuromorphic computing platform: the task is to thegoalistoacceleratetheunderstandingofbraindis- developandoperatenovelbrainderivedcomputing easesbyincreasingthevalueofexistingclinicalrecords hardware. anddatawithmoderndatastorageandmachinelearn- 6. Neurorobotics platform: the task is to develop ing technologies. By systematically understanding the virtualroboticsystemsforclosedloopcognitiveex- similarities and differences of brain diseases the HBP periments. expects to provide tools for pharmaceutical and nutri- tion companies to prevent, diagnose, and treat brain The platforms will be complemented by a new diseases. The future computing research area aims at European Institute for Theoretical Neuroscience to in- X tegratebasicresearchoninformationprocessinginthe goingresearchandtotheenableapermanentdiscourse brainandtousetheHBPplatformstoinspirenewthe- withthepublic. oreticalapproachestothestudyofthebrain.Also,the project will have a strong ethics group to monitor on- Heidelberg,July2013 KarlheinzMeier CurriculumVitae • since2011:Co-DirectoroftheEUHumanBrainProject,ETFlagshipProject • since2011:InvitedprofessoratEPFL(Lausanne,Switzerland) • since2010:CoordinatoroftheEUBrainScaleSConsortium • since2009:CoordinatoroftheMarie-CurieNetworkFACETS-ITN • 2005–2010:CoordinatoroftheEUFACETSConsortium • 1999:FoundingDirectoroftheKirchhoffInstitutfürPhysik • 1994–2012:ProjectleaderoftheLHC-ATLASTriggerPreProcessor • since1992:ChairExperimentalPhysics,Ruprecht-Karls-UniversitätHeidelberg • 1990–1992:ScientificStaff(tenure)atDESY(Hamburg) • 1988–1990:ScientificStaffatCERN(Geneva,Switzerland) • 1984–1988:ResearchFellowatCERN(Geneva,Switzerland) • 1984:PhDinPhysicsfromHamburgUniversity • 1981:DiplomainPhysicsfromHamburgUniversity FieldsofInterest Experimentalparticlephysics,microelectronicsinstrumentation,physicsfoundationsofinformationprocessing, brain-inspiredcomputing XI Preface Oneofthegreatestscientificachievementsofthetwen- tions in a computer system. This will enable a better tiethcenturywasthedecipheringofthehumangenome understanding of many cognitive processes and brain and the genomes of many other species. The Hu- diseases,suchasAlzheimer’sdisease,stroke,epilepsy, man Genome Project revealed the “mystery” of the Parkinson’sdisease,mentalretardation,andaging.The human genome and provided us with an enormous BRAINproject,foundedintheUSAalsoin2013,aims quantity of data and information that still needs to at the development of a broad set of activities for the be properly processed in order to obtain new knowl- studyofthehumanbrainincluding:keyinvestmentsto edge about the human race and its living environment jumpstarttheeffort,strongacademicleadership,public- on this planet, their biological co-evolution, their cur- private partnerships, and maintaining highest ethical rent state of development, and possibly, their future. standards. These scientific and technological advancements led The active research in bio- and neuroinformatics to the firm establishment of the science discipline and the vast amount of data and information, much of bioinformatics. New biological data, information, and it overlapping and strongly related, requires a unified knowledge have been produced in many institutes approachtotheanalysisofthisdataforthesakeofnew from all over the world, for example: the Euro- knowledgediscovery.Thisistobeprovidedbyinforma- pean Bioinformatics Institute, the National Centre for tionscienceasdemonstratedinthisSpringerHandbook Biotechnology Information, and the RIKEN Bioinfor- ofBio-/Neuroinformatics. maticsInstitute. TheSpringerHandbookwasachallengingproject, Itisagreedthatthetwenty-firstcenturywillbede- as for the first time it puts together both the founda- voted to the deciphering of the human brain. Several tions and the state-of-the art of three major science projectsandinstituteshavealreadyaddressedthischal- disciplinesintheirinteractionandmutualrelationship, lenge. The Blue Brain Project aimed at the computer namely: information science (IS), bioinformatics (BI), simulation of brain functions at a low level of brain andneuroinformatics(NI). informationprocessing.TheAllenBrainScienceInsti- tute has already mapped tens of thousands of human genestothebrainstructuresandfunctionsofmiceand humans, providing an enormous amount of data (see Chap.62). The goals of the RIKEN Brain Science In- Bioinformatics Neuroinformatics stituteforthetwenty-firstcenturyaretounderstand,to create, and to protect the brain (see the Foreword by Prof.Amari).Thereisaninternationalcoordinationof Information neuroinformaticsactivitiesintheInternationalNeuroin- Science formatics Coordinating Facilities, in which Japan has taken a leading role (see Part J). All these activities haveledtothefirmestablishmentofanotherscientific discipline–neuroinformatics. Recently, several new large-scale world projects The text contains 62 peer reviewed chapters orga- have started to generate by the hour new, large-scale nized in 12 parts, 6 of them covering topics from IS dataandinformationaboutthehumanbrain,including andBI,and6topicsfromISandNI.Eachchaptercon- data related to biology, physiology, psychology, cog- sistsofthreemainsections:introductiontothesubject nitive studies, and brain diseases. The Human Brain area,presentationofmethods,andadvancedandfuture Project was founded in 2013 by the European Union. developments. It includes more than 80 participants from Europe. It Some of the IS methods are presented separately, aims at collecting data at each level of brain function- someareusedtoaddressproblemsinBIor/andNI,but ing–molecular,genetic,proteomic,synaptic,neuronal there are also specific methods designed for BI or NI ensembles, and cognitive, and to simulate brain func- only. The BI and NI areas also share IS methods, as