Foreword: from the TRANSCRIPTOME conferences to the SYSTEMOSCOPE international consortium

This thematic issue issue of the Comptes rendus Biologies contains review articles, original papers and conference reports presented at the first two TRANSCRIPTOME conferences From Functional Genomics to Systems Biology and IMAGE Consortium Invitational workshops (Paris, November 2000 and Seattle, March 2002), and discussed during the inaugural meetings of the SYSTEMOSCOPE International Consortium (Paris, June 2003). We describe the founding principles, missions, working plan and policy for partnership and industrial development of SYSTEMOSCOPE to promote the study of the complexity of biological systems by integrating scientific, medical, ethical and economic issues in implementation of interdisciplinary projects for human health.     

Passing the Red Pen: EvoS Journal Offers an Early Education in Peer Review

EvoS Journal: The Journal of the Evolutionary Studies Consortium is the open-access, peer-reviewed journal borne of the EvoS (Evolutionary Studies) Consortium movement. The journal has two separate, yet related goals: to publish scholarly articles regarding the intersection of higher education and evolutionary theory, and to publish articles written and reviewed by undergraduates that incorporate an evolutionary perspective. Undergraduates who publish and review for EvoS Journal get the chance to see their work published alongside that of experts within the field of evolutionary studies, and to see the interdisciplinary and widespread applications of evolutionary theory to human life and beyond. The current study examines whether the interdisciplinary nature of EvoS Journal and its initiation of students into the peer-review process set EvoS Journal apart from more traditional undergraduate journals. EvoS Journal was compared to other journals listed by the Council for Undergraduate Research. While EvoS Journal mirrors many traditional undergraduate journals in their employment of student reviewers and publishing work originating from any U.S. institution, it differs by both its interdisciplinary focus and by serving as an outlet for both student and professional publications. The implications are discussed in terms of the benefits of interdisciplinary and peer-review training to students in the classroom, including improvements in writing, interpersonal relations, and real-world skills.     

wFleaBase: the <Emphasis Type="Italic">Daphnia</Emphasis> genome database

Background  

wFleaBase is a database with the necessary infrastructure to curate, archive and share genetic, molecular and functional genomic data and protocols for an emerging model organism, the microcrustacean Daphnia. Commonly known as the water-flea, Daphnia's ecological merit is unequaled among metazoans, largely because of its sentinel role within freshwater ecosystems and over 200 years of biological investigations. By consequence, the Daphnia Genomics Consortium (DGC) has launched an interdisciplinary research program to create the resources needed to study genes that affect ecological and evolutionary success in natural environments.     

The psychiatric GWAS consortium: big science comes to psychiatry

The Psychiatric GWAS Consortium was founded with the aim of conducting statistically rigorous and comprehensive GWAS meta-analyses for five major psychiatric disorders: ADHD, autism, bipolar disorder, major depressive disorder, and schizophrenia. In the era of GWAS and high-throughput genomics, a major trend has been the emergence of collaborative, consortia approaches. Taking advantage of the scale that collaborative consortia approaches can bring to a problem, the PGC has been a major driver in psychiatric genetics and provides a model for how similar approaches may be applied to other disease communities.     

The nature and identification of quantitative trait loci: a community's view

This white paper by eighty members of the Complex Trait Consortium presents a community's view on the approaches and statistical analyses that are needed for the identification of genetic loci that determine quantitative traits. Quantitative trait loci (QTLs) can be identified in several ways, but is there a definitive test of whether a candidate locus actually corresponds to a specific QTL?     

Building the contractile ring from the ground up: a lesson in perseverance and scientific creativity

This contribution to the Festschrift for Professor Thomas (Tom) D. Pollard focuses on his work on the elucidation of the protein organization within the cytokinetic nodes, protein assemblies, precursors to the contractile ring. In particular, this work highlights recent discoveries in the molecular organization of the proteins that make the contractile machine in fission yeast using advanced microscopy techniques. One of the main aspects of Tom’s research philosophy that marked my career as one of his trainees is his embrace of interdisciplinary approaches to research. The cost of interdisciplinary research is to be willing to step out of our technical comfort zone to learn a new set of tools. The payoff of interdisciplinary research is the expansion our realm of possibilities by bringing new creative tools and ideas to push our research program forward. The rewarding outcomes of this work under Tom’s mentorship were the molecular model of the cytokinetic node and the development of new techniques to unravel the structure of multi-protein complexes in live cells. Together, these findings open a new set of questions about the mechanism of cytokinesis and provide creative tools to address them.     

Marginal modeling of multilevel binary data with time-varying covariates

We propose and compare two approaches for regression analysis of multilevel binary data when clusters are not necessarily nested: a GEE method that relies on a working independence assumption coupled with a three-step method for obtaining empirical standard errors, and a likelihood-based method implemented using Bayesian computational techniques. Implications of time-varying endogenous covariates are addressed. The methods are illustrated using data from the Breast Cancer Surveillance Consortium to estimate mammography accuracy from a repeatedly screened population.     

The future of interdisciplinary research and training: how to conquer the silo guardians

We have entered a new era in biomedical research in which large interdisciplinary teams are being established to answer important scientific questions. Scientists of multidisciplinary backgrounds within universities are combining forces and inter-institutional consortia that include alliances between academia and industry are springing up around the country to generate breakthrough advances. A number of driving forces are at work to establish these collaborative research approaches. By contrast, there also are barriers to be surmounted by institutions with silo mentalities for effective partnerships to be established. In order for this new era of research to reach maximal effectiveness, new approaches to education of the young and retraining of established administrators and scientists must take place. These issues were explored thoroughly at the 2006 annual meeting of the Association of Anatomy, Cell Biology and Neurobiology Chairpersons (AACBNC) that was held in Aruba from January 18 to 21. The theme of this historic meeting was the Future of Interdisciplinary Research and Training: Breaking Down the Barriers. In this introductory article, we discuss the formation of a trendsetting Institute of Biomedical Sciences and Technology, the concept of the AACBNC meeting, and the influence of the Institute on the content of the meeting. The proceedings of this meeting, including Nobel Laureate Papers and Nobel Round-Table Discussions on the future of interdisciplinary research and training, are contained in this special issue of Experimental Biology and Medicine, a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences.     

Developmental plasticity in plants: implications of non-cognitive behavior

There has been a surge of interest in phenotypic plasticity in the last two decades. Most studies, however, are being carried out within relatively narrow disciplinary frameworks. Consequently, researchers differ not only in their scientific agenda; they often use different terminologies and conceptual frameworks even when studying the very same phenomena. The diversity of approaches has often generated parallel bodies of theory on subjects that can be best understood in broader interdisciplinary terms. This special issue points out the differences between the concepts and questions that are characteristic of various approaches. Bridging all gulfs may be impossible and not necessarily desirable, yet, awareness of the varied approaches should be instrumental in promoting interdisciplinary advances. It is the contribution to such awareness that is the major purpose of this special issue, and for this reason it deals with molecular, physiological, ecological and evolutionary approaches to the study of developmental plasticity. So as to focus the discussion, six topics have been selected, ranging from the fundamental essence of developmental plasticity to its implications to ecology and evolution. These topics were considered by scholars who were chosen for the diversity of their research, not only their expertise. Rather than a comprehensive body of theory, the current issue thus seeks the diversity of opinions on the discussed topics. It is hoped that the confrontation, in its original Latin sense, which includes bringing together and discussion, of scholars who are studying these phenomena at very different levels and from different points of view will generate new insights and promote future interdisciplinary research.     

Walking the Walk to Teach the Talk: Implementing Ancestral Lifestyle Strategies as the Newest Tool in Evolutionary Studies

The learning of evolutionary theory typically takes place in the classroom or laboratory. Students of these traditional approaches often leave with the notion that applications of evolutionary theory have little bearing on their lives. The Evolutionary Studies Consortium (EvoS; ) has been extremely successful in overcoming these barriers and demonstrating the bridges across academic areas that can be created with the principles of evolution as a guide. While this is a fantastic means through which to educate students about the intricacies of evolution, we believe that the full potential of this approach has yet to be realized. Applications beyond strict academic contexts are still waiting to be mined. Here, we outline an approach that proposes the implementation of a nutrition and physical fitness program, alongside classroom pedagogy, as a means of helping students learn about evolution and how it can be used to increase their own quality of life.     

A new paradigm for graduate research and training in the biomedical sciences and engineering

98Emphasis on the individual investigator has fostered discovery for centuries, yet it is now recognized that the complexity of problems in the biomedical sciences and engineering requires collaborative efforts from individuals having diverse training and expertise. Various approaches can facilitate interdisciplinary interactions, but we submit that there is a critical need for a new educational paradigm for the way that we train biomedical engineers, life scientists, and mathematicians. We cannot continue to train graduate students in isolation within single disciplines, nor can we ask any one individual to learn all the essentials of biology, engineering, and mathematics. We must transform how students are trained and incorporate how real-world research and development are done-in diverse, interdisciplinary teams. Our fundamental vision is to create an innovative paradigm for graduate research and training that yields a new generation of biomedical engineers, life scientists, and mathematicians that is more diverse and that embraces and actively pursues a truly interdisciplinary, team-based approach to research based on a known benefit and mutual respect. In this paper, we describe our attempt to accomplish this via focused training in biomechanics, biomedical optics, mathematics, mechanobiology, and physiology. The overall approach is applicable, however, to most areas of biomedical research.     

Coexistence research requires more interdisciplinary communication

Coexistence theories develop rapidly at the ecology forefront, outpacing their experimental testing. I discuss the reasons for this gap, call on interdisciplinary researchers to construct a road map for coexistence research, and recommend the actions that should be implemented therein.

Coexistence theories outpace their experimental testing. I argue that this imbalance results from a combination of interdisciplinary gaps, a disparity in research approaches, and the limited accessibility of the theory to experimentalists. I call on interdisciplinary researchers to construct a road map for coexistence research, recommend the actions that should be implemented therein, and illustrate how multiple mechanisms can be integrated under the same coexistence terms, thus constructing a research landscape that can create uniformity in their experimental designs.     

Pavlov and psychophysiology in the 21st century]

Psychophysiology, physiological psychology (Sechenov), human physiology of higher nervous activity (Pavlov) is an interdisciplinary field, which appeared at the interface between psychology and neurosciences for exploration of the brain mechanisms of mental functions. The fundamental complementation of subjective and objective, psychological and neurobiological approaches as the facets of investigation of the basically whole process made it possible to fill with a specific content and clearly differentiate the forms of human psyche such as emotion, consciousness, personality, character, and creativity.     

A method of Reflexive Balancing in a Pragmatic,Interdisciplinary and Reflexive Bioethics

In recent years there has been a wealth of literature arguing the need for empirical and interdisciplinary approaches to bioethics, based on the premise that an empirically informed ethical analysis is more grounded, contextually sensitive and therefore more relevant to clinical practice than an ‘abstract’ philosophical analysis. Bioethics has (arguably) always been an interdisciplinary field, and the rise of ‘empirical’ (bio)ethics need not be seen as an attempt to give a new name to the longstanding practice of interdisciplinary collaboration, but can perhaps best be understood as a substantive attempt to engage with the nature of that interdisciplinarity and to articulate the relationship between the many different disciplines (some of them empirical) that contribute to the field. It can also be described as an endeavour to explain how different disciplinary approaches can be integrated to effectively answer normative questions in bioethics, and fundamental to that endeavour is the need to think about how a robust methodology can be articulated that successfully marries apparently divergent epistemological and metaethical perspectives with method. This paper proposes ‘Reflexive Bioethics’ (RB) as a methodology for interdisciplinary and empirical bioethics, which utilizes a method of ‘Reflexive Balancing’ (RBL). RBL has been developed in response to criticisms of various forms of reflective equilibrium, and is built upon a pragmatic characterization of Bioethics and a ‘quasi‐moral foundationalism’, which allows RBL to avoid some of the difficulties associated with RE and yet retain the flexible egalitarianism that makes it intuitively appealing to many.     

Unlocking the bovine genome

The draft genome sequence of cattle (Bos taurus) has now been analyzed by the Bovine Genome Sequencing and Analysis Consortium and the Bovine HapMap Consortium, which together represent an extensive collaboration involving more than 300 scientists from 25 different countries.     

Using the Optimal Robust Receiver Operating Characteristic (ROC) Curve for Predictive Genetic Tests

Summary Current ongoing genome‐wide association (GWA) studies represent a powerful approach to uncover common unknown genetic variants causing common complex diseases. The discovery of these genetic variants offers an important opportunity for early disease prediction, prevention, and individualized treatment. We describe here a method of combining multiple genetic variants for early disease prediction, based on the optimality theory of the likelihood ratio (LR). Such theory simply shows that the receiver operating characteristic (ROC) curve based on the LR has maximum performance at each cutoff point and that the area under the ROC curve so obtained is highest among that of all approaches. Through simulations and a real data application, we compared it with the commonly used logistic regression and classification tree approaches. The three approaches show similar performance if we know the underlying disease model. However, for most common diseases we have little prior knowledge of the disease model and in this situation the new method has an advantage over logistic regression and classification tree approaches. We applied the new method to the type 1 diabetes GWA data from the Wellcome Trust Case Control Consortium. Based on five single nucleotide polymorphisms, the test reaches medium level classification accuracy. With more genetic findings to be discovered in the future, we believe a predictive genetic test for type 1 diabetes can be successfully constructed and eventually implemented for clinical use.     

The Plant Ontology Consortium and plant ontologies

The goal of the Plant Ontology Consortium is to produce structured controlled vocabularies, arranged in ontologies, that can be applied to plant-based database information even as knowledge of the biology of the relevant plant taxa (e.g. development, anatomy, morphology, genomics, proteomics) is accumulating and changing. The collaborators of the Plant Ontology Consortium (POC) represent a number of core participant database groups. The Plant Ontology Consortium is expanding the paradigm of the Gene Ontology Consortium (http://www.geneontology.org). Various trait ontologies (agronomic traits, mutant phenotypes, phenotypes, traits, and QTL) and plant ontologies (plant development, anatomy [incl. morphology]) for several taxa (Arabidopsis, maize/corn/Zea mays and rice/Oryza) are under development. The products of the Plant Ontology Consortium will be open-source.     

Surface and ultrastructural characterization of raw and pretreated switchgrass

The US Department of Energy-funded Biomass Refining CAFI (Consortium for Applied Fundamentals and Innovation) project has developed leading pretreatment technologies for application to switchgrass and has evaluated their effectiveness in recovering sugars from the coupled operations of pretreatment and enzymatic hydrolysis. Key chemical and physical characteristics have been determined for pretreated switchgrass samples. Several analytical microscopy approaches utilizing instruments in the Biomass Surface Characterization Laboratory (BSCL) at the National Renewable Energy Laboratory (NREL) have been applied to untreated and CAFI-pretreated switchgrass samples. The results of this work have shown that each of the CAFI pretreatment approaches on switchgrass result in different structural impacts at the plant tissue, cellular, and cell wall levels. Some of these structural changes can be related to changes in chemical composition upon pretreatment. There are also apparently different structural mechanisms that are responsible for achieving the highest enzymatic hydrolysis sugar yields.