AlzSWAN Knowledge Base

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FAQ

1. What is AlzSWAN?
   AlzSWAN is a community-driven knowledgebase of Alzheimer disease, in which researchers can annotate scientific claims, data, and information, putting these into the context of testable hypotheses and treatment discovery. AlzSWAN relies upon a moderated community process to capture the collective insights of the AD field, and welcomes and explicitly models disagreements and differing interpretations of data. AlzSWAN is enabled by Semantic Web technology, a new standard for knowledge organization and transfer on the Web. AlzSWAN organizes and manages knowledge using formal knowledge descriptions called ontologies. Using these formal knowledge descriptions, we can tie statements made in scientific publications or on the Web to scientific evidence, biological terminologies, and knowledgebases, and to claims and counterclaims made by other researchers.
2. How can I contribute to AlzSWAN?
   AlzSWAN is annotated by our curators and advisors and is currently in limited beta release. Upcoming features will enable users to generate comments and add annotation directly to the hypotheses, claims, and publications in the knowledgebase, and to download commented citations directly to their local EndNote libraries. Beta users are encouraged to comment freely on the functions and features of AlzSWAN's AD knowledgebase, to request changes, report bugs, and submit new content. AlzSWAN is constantly updating, adding hypotheses, comments, and other content, and we welcome our beta users to suggest or contribute new content.
3. Do I need to register to use AlzSWAN?
   In the current "limited beta" version, we would like everyone to sign in to use AlzSWAN Browser, and to be as active in commenting on AlzSWAN's content and features as they can. If you are interested in participating, please contact us.
4. How do I find hypotheses or claims that discuss a particular gene or protein?
   You can find scientific discourse linked to a specific gene or protein in three ways.
   1. From the Global Search box on the AlzSWAN home page (or in the upper right corner of the other pages). Global Search runs a semantic search across all text, and all relationships, in the AlzSWAN knowledgebase.
   2. By filtering the complete list of research statements by gene or protein name, under the menu Statements, select the class of research statement to search for a gene or protein of interest: Hypotheses, Claims, Comments, Questions. To search All statements, click on the voice Statements. Use the Free text search box on the right side bar to type in the name of a gene or protein of interest, for example, APP, tau, presenilin.
   3. Select Genes and Proteins from the Genes-Proteins list.
      An alphabetized list of Genes and Proteins linked to AlzSWAN research statements will appear. You may prune the list either by typing a name into the Free text search box or by searching the list. You may also limit your selection by species using the selector window in the right side bar. When you find the gene or protein of interest, click on its name to see further details including all linked research statements
5. How do I find hypotheses or claims that discuss a particular stage of Alzheimer pathogenesis?
   You can find scientific discourse linked to a specific stage of Alzheimer pathogenesis. We use a simple model of four pathogenic which we call a "Pathogenic Narrative." The four stages are: Initial Conditions; Perturbation; Pathogenic Event; Pathologic Change. Every claim in AlzSWAN is classified within one or more of these stages. In the Claims list window, in the right side bar, you may filter Claims using Pathogenic Narrative as a selector. (See Question 9.)
6. What is a hypothesis?
   In AlzSWAN, both hypotheses and claims are "Statements", with authors, curators, and date of origin identified. A hypothesis is a statement proposing one or more ideas that concern the cause or development of Alzheimer disease, which has a provisional nature. There are two forms of hypotheses in AlzSWAN: those with simple annotation and those with extended annotation. A hypothesis with simple annotation is a statement, and a brief description, with an author and date of the statement. It has not yet been broken down into individual claims. Hypotheses with extended annotation contain an ordered narrative of claims tied to evidence and other ontological terms.
7. What is Extended Annotation?
   In AlzSWAN, a hypothesis with extended annotation is itself composed of a number of individual research statements called claims (see below). Such a hypothesis contains the title statement, a description, author(s), date of publication, and then adds in a wealth of new information through the list of claims contained within the hypothesis. This new information includes a set of published evidence selected by the author to support the hypothesis, links to genes or proteins, and relationships among claims to reflect the degree of general acceptance of the ideas proposed.
8. What is a claim?
   A claim is a research statement that is accepted by the author as reasonable. Unlike a hypothesis, its author does not consider it provisional, but proven. Claims may be strung together in a "claims narrative" which composes an overarching hypothesis. A claim has an author or a set of authors, and may be linked to published evidence to support or discuss the assertion made. It may also be linked to a specific gene or protein (see Life Science Entities). In addition, a claim may be linked to other discourse through relationships such as "Consistent with", "Inconsistent with", "Alternative to", or "Discusses".
9. What is the Pathogenic Narrative?
   The pathogenic narrative is a simple, intuitive set of terms that biomedical researchers can use to classify research statements in the context of the Alzheimer disease pathogenic process. Every claim in AlzSWAN is tagged with a Pathogenic Narrative term, thereby allowing researchers to see at a glance which hypotheses focus on any particular stage of disease pathogenicity. Note: individual researchers may differ in how they classify the same observation, depending on the hypothesis context.
   Note: individual researchers may differ in how they classify the same observation, depending on the hypothesis context.

   Pathogenic Narrative Term	Definition	Examples
   Initial condition	Innate genetic and biological, biochemical characteristics	Genes, gene mutations, chromosome aberration, normal molecular and cellular pathways, intrinsic properties
   Perturbation	Clinical perturbations: Life events and environmental factors that alter the risk of disease	Head trauma, history of taking statins or NSAIDs, diet low in omega-3 fatty acids, education, aging, etc.
   	Experimentally induced perturbations	Overexpression of genes in cell culture; increased gene copy number (transgenesis or transfection); growing cells in oxygen deprivation, inhibitors
   Pathogenic event	Abnormal molecular cascade initiated by the perturbing factors	Increase in Abeta production, Abeta accumulation, Abeta oligomerization, tau hyperphosphorylation, change in calcium homeostasis, oxidative stress, proteasomal dysfunction, etc.
   Pathologic change	Frank disease state; damage or dysfunction of cells or systems	Loss of NGF, inflammation, intracellular protein aggregation, extracellular plaque, apoptosis, necrosis, loss of dendrites, axon terminals, nerve processes, demyelination, cell loss, etc.

10. What is "Experimental Approach"?
    The experimental approach ontology provides a simple framework for classifying complementary types of experimental data. A complete disease hypothesis ideally should be supported by evidence from all of these categories.

    Ontology Term	Definition	Examples
    Genetics	Pertaining to genes, genetic basis of normal and pathological stat	Familial AD mutations in APP, PS1, PS2; ApoE4 and other risk-associated genes, tau mutations, etc.
    Epidemiology	Factors which are associated with disease; attributions of disease in defined populations, incidence, frequency, prevalence	Medications (NSAIDs, statins, estrogen); diet; diabetes, cardiovascular disease; etc.
    Pathophysiology	Describes the disease state; includes structural and physiological abnormalities at the anatomical, organ, cellular, and subcellular levels	Amyloid and tau lesions; astrogliosis; lipid peroxidation; loss of synaptophysin in AD brain; patterns of dendritic, axonal, and cell loss in AD brain; etc.
    Mechanism-biochemistry and structural biology	Describes static and dynamic structural and chemical properties and interactions of biological molecules, including sugars, lipids, proteins, RNA, DNA, etc.	Abeta oligomerization and fibril formation, Abeta:ApoE interactions, secretase-mediated cleavage of APP, etc.
    Mechanism-molecular and cell	Chiefly concerned with interactions between various systems of a cell, including interrelationship of DNA, RNA, and protein synthesis and learning how these interactions are regulated	Regulation of APP expression, role of Abeta in neuronal plasticity, role of tau in axonal transport, role of proteasome dysfunction, etc.
    Mechanism-physiological systems	Concerns information transmission and regulation of cells in a multicellular context, including within a tissue or organ, between organs, and between physiological systems	Studies of a neural signaling network, signaling between immune molecules and nerve cells, interaction of vascular system and the blood-brain barrier, etc.
    Neuropsychology/behavior	Describes external behavior and cognitive functions in animals and humans, investigates connection between external behavior and neurophysiological processes	Studies of aggression, anxiety, learning, and memory, etc., in model organism; studies of performance on cognitive tests in patients; studies of aggressive behavior in patients; etc.
    Biomarkers	Describes measurable biological parameters (e.g., specific protein concentration, genotype) which serve as indices of health and physiology-related assessments of disease risk, diagnosis, disease stage, treatment response, mechanism-based animal model, etc.	Protein, lipid and other biomolecules in blood, CSF, urine, etc.; markers in biological samples such as skin fibroblasts; correlation of ApoE genotype with physiological markers; etc.
    Target validation	Describes a specific target for therapy by drugs, diet, or other interventions, and the effect of such interventions on disease processes or state	Compound X inhibits BACE1 cleavage of APP; deletion of tau eliminates cognitive deficit in APP mutant mouse, etc.
    Animal models	Describes a non-human animal system that exhibits specific mechanisms, pathology, or other characteristics relevant to the disease	Natural aged species, genetically modified species, lesion models, etc.
    Clinical trials	Describes preplanned studies of the safety, efficacy, or optimum dosage schedule of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects	Phase 1-4 trials of drugs, vaccines, gene therapy, devices, dietary supplements, behavioral interventions, etc.

11. What is Evidence?
    Evidence in its broadest sense includes anything that is used to determine or demonstrate the validity of an assertion. In AlzSWAN, evidence is currently limited to published and peer-reviewed data. Most evidence in AlzSWAN has a PubMed ID number.
12. What is an Evidence Map?
    An evidence map is a unique aspect of AlzSWAN that allows a researcher to see the relationships between claims and evidence. In AlzSWAN, a claim may cite a published journal article, and from that initial claim one may link to this citation. The citation page then provides a list of all other claims in AlzSWAN that cite this article. In this way hypotheses and claims are linked through common citations of evidence, and claims and evidence links are identified.
13. How do I cite AlzSWAN?
    Please cite AlzSWAN in any publications by referencing these two publications:
    1. Clark T and Kinoshita J (2007) Alzforum and SWAN: The Present and Future of Scientific Web Communities. Briefings in Bioinformatics 8: 163-171; doi:10.1093/bib/bbm012
    2. Ciccarese P, Wu E, Wong G, Ocana M, Kinoshita J, Ruttenberg A and Clark T (in press). The SWAN Biomedical Discourse Ontology. Journal of Biomedical Informatics.
14. How do I cite AlzSWAN content?
    We recommend using the AMA citation style. Here is an example:
    Todd E Golde. The Abeta hypothesis will lead to rationally-designed therapeutic strategies for the treatment or prevention of Alzheimer disease. AlzSWAN Alzheimer Knowledge Base. May 20, 2008. Available at: http://hypothesis.alzforum.org/swan/browser/swanEntityView.action?objectId=urn:lsid:swan.org:researchstatement:9d11160e-94ad-4760-92a9-591e1d221769 Accessed on: May 26, 2008.
15. How do I report a problem, request a feature, or suggest new content with/for AlzSWAN?
    Contact us; we'll respond as quickly as possible. We are grateful for all your ideas, suggestions, and observations.

©2007-2010 AlzSWAN content copyright Alzheimer Research Forum
©2008-2010 SWAN software copyright Massachusetts General Hospital
Created by the SWAN Development Team
We thank the Ellison Medical Foundation and Alzheimer's Association for their generous grant support.
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