The Hypothesis Web


The Hypothesis Web



What is the Hypothesis Web?



A major obstacle to interdisciplinary research is the formulation of hypotheses that span multiple fields of expertise. This is particularly true for scientific research, which can involve aspects of very diverse disciplines at many physical scales. In neuroscience, for example, combined efforts involving multiple disciplines can be necessary in order to make any substantial progress.

The Hypothesis Web is a project at UCLA investigating the development of a software platform that permits collaborative formulation of complex scientific hypotheses. It represents a novel approach to the way these hypotheses are conceived and tested, in which: The Hypothesis Web is being developed as an extension of existing software systems for web-based collaboration, data management, modeling, and access of online scientific literature.

This project is one of eight projects within the new Consortium for Neuropsychiatric Phenomics (CNP), an NIH Interdisciplinary Research Center at UCLA emphasizing integrative research spanning multiple levels of science. The system will be used for collaborative development of hypotheses within the other CNP projects.




September 6, 2007
Contact: Mark Wheeler
Phone: 310-794-2265

UCLA News Release:
UCLA Receives $22.5 Million to Explore the Fundamental Biology of Mental Disorders

The National Institutes of Health has awarded $22.5 million to a team of scientists centered at the Semel Institute for Neuroscience and Human Behavior at UCLA to fund the Consortium for Neuropsychiatric Phenomics (CNP), an interdisciplinary, campuswide effort to understand the biology underlying a variety of mental disorders.

Phenomics is the study of an organism's full complement of phenotypes those manifest characteristics, ranging from single proteins to anatomical traits and complex behaviors, that result from the organism's genetic makeup and environment, said Robert Bilder, UCLA professor of psychiatry and director of the new consortium. Understanding an organism's phenotype is the next logical step following the recent decoding the human genome. That decoding effort, which discerned the DNA sequences that form the basic instructions for biological processes, was designed to enable the identification of genetic variations responsible for the major diseases that plague humankind.

Phenomics takes a more "holistic viewpoint," Bilder said. "To understand how these genetic variations are associated with disease now requires the decoding of the human phenome, the sum of the physical and behavioral manifestations of those genetic variations and how they interact with the environment.

"Understanding the fundamental biological bases of neuropsychiatric disease from the molecule to the mind is an enormous challenge and will offer a grand challenge to biomedical research for the rest of the century," he said.

Currently, psychiatrists do not possess the types of laboratory tests or biological models that can be useful in studying these disorders, Bilder said.

"The diagnostic systems we have in place are widely acknowledged to be flawed, because the phenotypes we have are not based on research but are descriptive," he said. "That is, they are based on symptoms we usually learned about, ironically, from asking patients who have disorders that make communication difficult.

"We so far lack markers to identify more fundamental deficits," he said. "We need to drill down and get closer to the specific level where a gene might be responsible for the process."

That is the goal of the consortium, which will target the behavioral and cognitive functions thought to underlie such neuropsychiatric syndromes as schizophrenia, bipolar disorder and attention deficit hyperactivity disorder.

In a departure from science-as-usual, the consortium will aim to discover the underpinnings of basic, healthy functioning systems such as memory and impulse control rather than concentrating on the genetic anomalies that may be associated with the neuropsychiatric disorders themselves. By focusing on these healthy brain systems, the researchers hope to accelerate the discovery of genes that are relevant to mental disorders and to find new treatments.

Employing a broad approach to attacking this problem, the consortium team comprises 52 investigators, many affiliated with the Semel Institute but cutting widely across campus disciplines as well, with members from the fields of psychiatry, neurology, neurobiology, human genetics, psychology and computer science collaborating and sharing data. Subawards will support research in Finland (at the universities of Helsinki and Oulu), at the University of California, Santa Barbara, and at the Medical University of South Carolina.

This interdisciplinary approach is a major goal of the consortium, which is one of nine nationwide being funded by the NIH's Roadmap for Medical Research program. The Roadmap program is designed not only to address health challenges that have been resistant to traditional research approaches but to fundamentally change how research is conducted, by integrating a wide range of disciplines to attack a problem. As opposed to multidisciplinary research, which involves teams of scientists approaching a problem from within their own disciplines, interdisciplinary research integrates elements from a wide range of disciplines, often including basic and clinical research, behavioral biology, and social sciences, so that all of the scientists may approach the problem in a new way.

"The interdisciplinary research programs within the Roadmap embody a central goal of this program to help transform the way research is conducted," said Dr. Elias A. Zerhouni, NIH director. "These programs are designed to encourage and enable change in academic research culture to make interdisciplinary research easier to conduct for scientists who wish to collaborate in unconventional ways."

"Our team is thrilled to have this opportunity to forge a unique path in neuropsychiatry research," Bilder said. "Many scientists and clinicians already acknowledge major limitations in the current system for diagnosing and treating patients. We believe the CNP strategy strongly complements existing approaches and offers new hope for discovery."

For more information about the consortium, visit www.phenomics.ucla.edu.

The Semel Institute for Neuroscience and Human Behavior at UCLA is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders. In addition to conducting fundamental research, the institute faculty seeks to develop effective treatments for neurological and psychiatric disorders, improve access to mental health services, and shape national health policy regarding neuropsychiatric disorders.

Related National Institutes of Health (NIH) News Release:
NIH Launches Interdisciplinary Research Consortia.




PubAtlas


As part of its software infrastructure, the Hypothesis Web project is developing PubAtlas, a program that acts as a front-end to PubMed.
As input PubAtlas takes two sets of "terms", which are text lines having one of the two formats
PubMed Query
concept phrase : PubMed Query
and analyze them in a table of associations.

For example, we could find associations between people and genes. Our first set of terms can then be queries about people:
#  Project Direction
Bob Bilder:                 Bilder Robert  [FAU]  OR  Bilder R   [AU]  # Director of CNP
Roberto Peccei:             Peccei Roberto [FAU]  OR  Peccei R   [AU]
Leonard Rome:               Rome Leonard   [FAU]  OR  Rome LH    [AU]
Fred Sabb:                  Sabb Fred      [FAU]  OR  Sabb FW    [AU]

#  Cognitive Neuroscience
Carrie Bearden:             Bearden Carrie [FAU]  OR  Bearden CE [AU]
Bob Bilder:                 Bilder Robert  [FAU]  OR  Bilder R   [AU]
Ty Cannon:                  Cannon Tyrone  [FAU]  OR  Cannon TD  [AU]
...

The second set of terms can be queries about gene identifiers, like these:
DAT1:       "DAT1" [TIAB] OR "DAT-1" [TIAB]
DRD2:       "DRD2" [TIAB] OR "DRD-2" [TIAB] OR ("D2" [TIAB] AND "dopamine receptor" [TIAB])
DRD4:       "DRD4" [TIAB] OR "DRD-4" [TIAB] OR ("D4" [TIAB] AND "dopamine receptor" [TIAB])
DRD5:       "DRD5" [TIAB] OR ("D5" [TIAB] AND "dopamine receptor" [TIAB])
SNAP2:      "SNAP2" [TIAB] OR "SNAP-25" [TIAB]
...
PubAtlas takes these two sets of terms and evaluates all PubMed associations between the first set (people) and the second (genes), and yields a table like the following:

blast_results.jpg


PubAtlas also has a number of predefined term sets — vocabularies of typically about 100 terms that can be used as "shotgun" association finders. The table above can be generated easily by just using the predefined sets for CNP people and CNP genes, with an input screen like this:
blast_query.jpg

For more information see the PubAtlas Tutorial.

The PubAtlas Gallery also has examples that quickly show what is possible.

Familiarity with PubMed can help you succeed with PubAtlas. There is an extensive online tutorial/reference/help system for PubMed. The PubAtlas query page has links to information about important PubMed features. This knowledge is important; being aware of how PubMed interprets queries enables you to find associations (and relevant publications) that otherwise might be missed. Spending 10 minutes looking through this may end up saving you hours of search.

Awareness of MeSH, the Medical Subject Heading "ontology" used by PubMed, is also important. MeSH is a kind of keyword index, or set of indexing terms or topics. As articles are entered into PubMed they are tagged by curators as being relevant to certain MeSH terms, so that we can search articles by topic.

Acknowledgements




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Consortium for Neuropsychiatric Phenomics

UCLA Semel Institute, Room C8-849    760 Westwood Plaza, CA 90095
Phone: 310-825-9474    Fax: 310-825-2850    E-mail: rbilder@mednet.ucla.edu



Copyright © 2007–2009 Consortium for Neuropsychiatric Phenomics    All Rights Reserved.