A major obstacle to translational research is the formulation of hypotheses that span multiple levels ofbiomedical research. This is particularly true for complex neuropsychiatric disorders, which involve aspectsof many scientific disciplines at many physical scales. Combined efforts involving multiple disciplines areneeded in order to make any substantial progress. We propose development of a software platform calledthe Hypothesis Web that permits collaborative formulation of complex scientific hypotheses. It represents anovel approach to the way scientific hypotheses are conceived and tested, in which: (1) hypotheses are thefocus of collaboration; (2) literature, data, and annotations are organized in a usable interface; (3)translational research groups work together to develop a web site for the hypothesis that containsaccumulated evidence; (4) hypotheses that span multiple levels are represented as hierarchical graphs; (5)hypotheses can be inspected analytically with tools like meta-analysis; (6) resulting hypothesis web sites canbe shared, modularized, and published.We propose to develop this platform as an extension of existing open-source systems for web-basedcollaboration, data management, modeling, and access of online scientific literature. Specifically: a wiki-likeplatform augmented for collaborative refinement of hypotheses. The Hypothesis Web representshypotheses visually as labeled graph models that identify the relevant concepts and associations. Thisgraphical approach permits visual specification of hypothesized models of different kinds, including pathwaydiagrams, measurement models, and structural equation models. The graphs can then be represented in 2Dcartographic displays that we refer to as Hypothesis Maps. Our design for the Hypothesis Web builds onmany results for phenotype analysis developed under our P20 planning grant (P20RR020750). The systemwill be used to record hypotheses developed by Consortium Projects. It will be developed as an extension ofexisting open-source systems, and be made freely available as it evolves over the duration of this project.We also propose development of a platform for producing a Phenomic Atlas, using the Hypothesis Web as afoundation, but extended with knowledge-based capabilities for exploration. Conceptually a related set ofHypothesis Webs can be bundled together to form an Atlas. Thus the Atlas is a medium for publication thatpermits dissemination of a collection of related Maps (hypotheses). In collaboration with ConsortiumResearch Projects we will construct Phenomic Atlases.
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