Hoeng, J.

Jurisica, I.

Meyer, P.

Peitsch, M.C.

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Vol. 31 no. 4 2015, pages 451–452BIOINFORMATICS EDITORIAL doi:10.1093/bioinformatics/btv065Systems biology Advance Access publication January 31, 2015Where are we at regarding species translation? A review of thesbv IMPROVER challengeJ. Hoeng1, M.C. Peitsch1, P. Meyer2 and I. Jurisica3,4,*1Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neucha^tel, Switzerland 2IBM T.J.Watson Research Center, Computational Biology, Yorktown Heights, NY 10598, USA, 3Department of ComputerScience and 4Department of Medical Biophysics, University of Toronto, Toronto, Ontario, CanadaAssociate Editor: Janet KelsoContact: Julia.Hoeng@pmi.comReceived on October 7, 2014; revised on January 21, 2015; acceptedon January 27, 2015Animal models serve an important purpose in fundamental re-search aimed at understanding the molecular networks under-pinning biological and cellular mechanisms. In drugdevelopment and toxicological risk assessment, compound test-ing usually starts by in vitro experiments, followed by in vivotesting using rodents as a mammalian model. This practice as-sumes that such animal models respond to active substancesthrough similar mechanisms. Yet in spite of many effectiveuses of animal models, numerous findings have also been unsuc-cessfully translated to humans, as evidenced by the failure ofmany clinical trials. These failures clearly stem from our lackof detailed understanding of inter-species differences that pre-cludes na€ıve translation of knowledge derived from animalmodels directly to human, but also further distinction amongavailable rodent models, including xenograft, genetic or syngen-eic models. Such limitations are driving the development ofincreasingly more complex in vitro systems, ranging from 3D-organoid tissue cultures derived from primary cells to so-calledhuman Organs-on-chips (Huh et al., 2013) and Human-on-a-chip (Marx et al., 2012). However, it is still early days,and replacing complex model organisms with a battery ofin vitro systems that adequately recapitulates human biology isa journey that has just begun.In this context, a pertinent question to ask is ‘to what extentperturbations induced in rodent cells are conserved and hencepredictable, in human cells?’This important question was addressed in the form of a chal-lenge titled ‘Species Translation Challenge’ in the framework ofsbv IMPROVER (systems biology verification, IndustrialMethodology for PROcess VErification in Research) (Meyeret al., 2012), a collaborative initiative by IBM Research andPhilip Morris International (PMI) R&D that uses crowd-sour-cing approaches to address fundamental questions in systemsbiology. For 4 months, starting in May 2013, the SpeciesTranslation Challenge was articulated around four sub-challenges focusing on different aspects of translatability withinand between species. The results of this challenge provide insightson (i) the accuracy of predictions in the context of the diversityand dimensionality of data types generated at various levels ofthe biological system; (ii) the importance of temporal informa-tion (more time points) to gain resolution in sequential molecularevents, especially if the activation time window is shifted betweenspecies; (iii) heterogeneity of results from similar computationalmethods, which is probably due to different methodologicalchoices made at distinct steps of the process (e.g. data prepro-cessing, feature selection, classification algorithm) that are prob-lem dependent; (iv) a consensus network that describes theconservation and divergence of biological pathways and inter-actions in response to a subset of stimuli. A total of 28 teams,comprising 51 scientists from 14 countries across Europe, NorthAmerica, Asia and Australia submitted predictions. The submis-sions of each team were evaluated by an independent panel ofscientists and the results of the Species Translation Challengewere presented, and best performers were rewarded at the sbvIMPROVER Symposium last October 2013 in Athens, Greece.Three best-performing teams were recognized in the first sub-Challenge. Team AMG involved scientists from University ofCalifornia Santa Barbara (USA), University of Groningen(Netherlands) and Rutgers University (USA). The other bestperformers in this sub-Challenge were Clemson University(USA) and Wayne State University (USA). Team AMG wasalso best performing in sub-Challenges 2 and 3. Five teamswere recognized as joint best performers in sub-Challenge 4:one from Max Planck Institute for Dynamics of ComplexTechnical Systems (Germany), a Swiss team from University ofLausanne and Institute of Bioinformatics, one from PacificNorthwest National Laboratory (USA) and two separateteams from University of Pittsburgh (USA). Details of eachteam are published on the sbv IMPROVER website (http://www.sbvimprover.com).This issue of Bioinformatics contains six articles dedicatedto the overall results, and the detailed description of best-performing computational methods that arose from the SpeciesTranslation Challenge.The current work constitutes a proof of principle thatthe molecular responses induced by active substances in anin vitro system are to some extent predictive of the responsesobserved in the same system of another species. A more detailedunderstanding of the range of applicability of the translation con-cept will impact the predictability of signaling responses, mode ofaction and efficacy of drugs in the field of systems pharmacology*To whom correspondence should be addressed. The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com 451as well as increase the confidence in the estimation of human riskfrom rodent data in the context of toxicological risk assessment.Details about the experimental methods and publicly released dataare available online (Poussin et al., 2014).Conflict of interest: none declared.REFERENCESHuh,D. et al. (2013) Microfabrication of human organs-on-chips. Nat. Protoc., 8,2135–2157.Marx,U. et al. (2012) ‘Human-on-a-chip’ developments: a translational cut-ting-edge alternative to systemic safety assessment and efficiency evalu-ation of substances in laboratory animals and man? Altern. Lab. Anim.,40, 235–257.Meyer,P. et al. (2012) Industrial methodology for process verification inresearch (IMProVeR): towards systems biology verification. Bioinformatics,28, 1193–1201.Poussin,C. et al. (2014) The species translation challenge—a systems biologyperspective on human and rat bronchial epithelial cells. Scientif. Data, 1,140009.452J.Hoeng et al.

Where are we at regarding species translation? A review of the sbv IMPROVER challenge

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Where are we at regarding species translation? A review of the sbv IMPROVER challenge

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