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.
- hypotheses are the focus of collaboration.
- literature, data, and annotations are combined within a single system.
- interdisciplinary research groups work together to develop a web site
for a given hypothesis that organize a group's accumulated evidence.
- resulting hypothesis web sites can be shared, modularized, and published.
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
UCLA News Release:
$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
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,
"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
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
For more information about the consortium, visit
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
National Institutes of Health (NIH) News Release:
NIH Launches Interdisciplinary Research Consortia.
As part of its software infrastructure, the Hypothesis Web project is developing
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
and analyze them in a table of associations.
concept phrase : PubMed Query
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:
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:
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 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:
For more information see the
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.
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.
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.
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