New buzz at Boston's Drug Discovery Technology conference

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  • There was a level of excitement andparticipation at IBCs Drug DiscoveryTechnology 2003 conference that had notbeen visible for at least a year, and it wasgood to see renewed interest in informatics.This years Boston extravaganza was wellattended, with packed rooms at most of thepresentations and a full house in theexhibitors hall.

    Overall, it is recognized that for drugdiscovery to advance and be more efficient,it will require innovations in the handling,consolidation and processing of all forms ofdiscovery data, coupled with support fordissemination and interpretation of researchinformation.There has been a noticeableshift from informatics being a disciplinesolely confined to informatics groups, to onethat is more accessible to scientists.Scientists need to understand and query thedata to properly interpret it, and manyresearch groups in companies are exploringnew ways of offering up the info assets to thedecision makers.

    The major themes of the informaticssession could be organized into threegroups: first, knowledge management;second, biological pathway analysis; and third,new IT development strategies.These areasappear to have come of age as the fields ofbioinformatics and genomics have becomemore mainstream. In addition topresentations, the session also includedworkshops and birds-of-a-featherdiscussion groups, allowing attendees todrive and respond to specific issues theyshared.

    On the topic of knowledge management,speakers from Curagen, GSK,AstraZeneca,Hoffmann-La Roche,Aventis, NuGensesis,Tripos and Beyond Genomics presentedhow effective use of knowledge from

    consolidated experiments as well as curateddata and literature sources could be used toreduce the time and costs of the drugdiscovery process. It was evident from thediscussions that knowledge managementwithin the context of drug discovery and lifesciences is a distinct approach from classicalknowledge management, relying on theconsolidation of all experimental data withmultiple integrated data sources, andsupporting scientific annotations.

    Many speakers described how suchon-line knowledge can be appliedthroughout the drug discovery process,from target discovery and validation, tohigh-throughput screening and designing ofcompounds, and finally to better designedclinical trials.A few of the presenters, suchas Jim Fickett from AstraZeneca(, went on todescribe how knowledge management wasintegral for the effectiveness of nascentfields such as systems biology.What is alsonew and refreshing to hear is howknowledge management needs to become aresource not only for informaticists but alsofor scientists as a decision supportinstrument. Rendered knowledge is ofpractical use only if it can be applied tosupporting effective decision making that canreduce the costs and times associated withdrug development, while improving thequality, safety and utility of therapeutics.Thecurrent combined development andregulatory costs per new drug of more than$890 million (press release from TuftsCenter for the Study of Drug Development,13 May 2003) are one of the primary drivers for developing and using aknowledge-based approach that wouldreverse the spiralling cost increase in drugdevelopment.

    Another area of common interest wasthe elucidation and use of biologicalpathways in drug discovery. Both MillenniumPharmaceuticals ( AstraZeneca discussed their internalprojects for organizing prior knowledge ofpathways to aid in the analysis oftranscriptional profiling and target validationstudies. Millenniums PARIS project, whichstands for PAthway Resource and InformationSystem, is a result of collaboration withIngenuity Systems ( system represents a graph of metabolicand signaling protein networks, somederived from the public databases LIGANDand CSNDB, as well as from proprietaryinformation gleaned from the literature.

    As the interest around systems biologygrows, the need for pathway databases andtools will continue to increase. For most,these are seen as adjuncts to atranscriptomics or functional genomicsapproach, yet pathways are believed by someto offer better understanding of biochemicalphenomena, and might become invaluablefor studying metabolic disorders or findingnew therapeutic strategies on signalingpathways. Indeed, the hope is that, throughthe elucidation of pathways, more completeknowledge will be gained about diseasemechanisms and therapeutic modes ofaction.This could have major implications infinding better (more efficacious) targeteddrugs with fewer side effects, and perhapscompounds that can be shown to havemultiple applications.

    Although pathway databases such asKEGG and EcoCYC have been around for awhile, the emphasis now is on supporting the context of pathways.That is, how a specificpathway functions within a given tissue orunder certain conditions (e.g. disease).

    BIOSILICO Vol. 1, No. 5 November 2003

    1478-5282/03/$ see front matter 2003 Elsevier Science Ltd. All rights reserved. PII: S1478-5282(03)02371-2158



    New buzz at Bostons Drug DiscoveryTechnology conferenceEric K. Neumann, Beyond Genomics, Drug Discovery through Systems Biology, 40 Bear Hill Road,Waltham, MA 02451, USA;e-mail:

  • Context is critical if researchers need toknow the specificity or responsiveness of atarget within a pathway.This is somethingthat has yet to be captured by anyinformatics system, but it will invariably betied to greater utility and even IP definitionsin the near future.To a large extent,pathways data and knowledge managementare seen to go hand in hand, both being usedto make important decisions, and bothrelying on context. It is interesting toconsider that perhaps we are witnessing theemergence of a new informatics paradigm,where knowledge becomes a formallydefined and well-shared scientific andeconomic asset.

    The third topic that was discussed by afew was the development of new ITstrategies to improve informatics

    infrastructure within large companies.Several speakers presented new andeffective methodologies to design and buildcomplex informatics systems that willeventually become the backbone of drugdiscovery platforms. Richard Ashe describedaccelerated software development programswithin GSK ( that canadapt more effectively to changing discoveryrequirements. Using lightweightmethodologies and web-based servicesrather than monolithic designing principles,projects could be defined and completedfaster within an ever-changing world ofneeds. Roy Dunbar, CIO of Eli Lilly( proposes moreeffective collaborations between IT andscientists to create applications that havemore utility. Juergen Seega from Abbott

    Laboratories ( describedkeeping the scientific and IT worlds in sync,rather than at odds.Taken together, IT isprogressing from being hidden in thebackwaters of software tinkering, tobecoming a major strategic partner withindrug discovery environments.

    Other issues were addressed, includinggood laboratory practices as related toinformatics, electronic notebooks,intelligent storage and use of high-throughput screening data, and IP portfoliomanagement. Based on the presentations atthe conference, it was clear that theapplications and benefits of informatics forthe pharmaceutical industry are growing,and that informatics promises to be a keyfactor for the future success of drugdiscovery.

    Systems biology is characterized by synergisticintegration of theory, computational modeling,and experiment [1]. Although softwareinfrastructure is one of the most crucialcomponents of systems biology research,there has been no common infrastructureor standard to enable integration ofcomputational resources.To solve thisproblem, the Systems Biology MarkupLanguage (SBML) [2] and Systems BiologyWorkbench (SBW) have been developed

    [3]. SBML is an open, XML-based format forrepresenting biochemical reaction networks,and SBW is a modular, broker-based,message-passing framework for simplifiedintercommunication between applications.Several simulation and analysis softwarepackages already support SBML (Level-1)and SBW, or are being developed to supportthem.

    Identification of the logic and dynamics ofgene-regulatory and biochemical networks is

    a major challenge of systems biology.Webelieve that such network building tools andsimulation environments using standardizedtechnologies play an important role in thesoftware platform of systems biology.As onesuch approach, we have developedCellDesigner, a process diagram editor forgene-regulatory and biochemical networks.

    In the following, we will introduce themain features of CellDesigner.The mostcrucial elements are that it is a system of

    BIOSILICO Vol. 1, No. 5 November 2003

    1478-5282/03/$ see front matter 2003 Elsevier Science Ltd.All rights reserved. PII: S1478-5282(03)02370-0



    CellDesigner: a process diagrameditor for gene-regulatory andbiochemical networksAkira Funahashi*, Mineo Morohashi and Hiroaki Kitano, Kitano Symbiotic Systems Project, ERATO, Japan Science and Technology Corporation, Suite 6A, M31,

    6-31-15 Jingumae, Shibuya-ku,Tokyo 150-0001 Japan. Hiroaki Kitano, The Systems Biology Institute, Suite 6A, M31, 6-31-15 Jingumae, Shibuya-ku,Tokyo 150-0001, Japan.

    Naoki Tanimura, Fuji Research Institute Corporation, 2-3 Kanda Nishikicho, Chiyoda-ku Tokyo 101-8443, Japan. Hiroaki Kitano, Sony Computer Science Laboratories, Inc.,

    3-14-15 Higashi-Gotanda, Shinagawa,Tokyo 141-0022, Japan. Hiroaki Kitano and Mineo Morohashi, School of Fundamental Science and Technology, Keio University,

    3-14-1 Hiyoshi, Kohoku-ku,Yokohama 223-8522, Japan. *e-mail: