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LAMHDI: The Search for Animal Models Starts Here  
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About LAMHDI

LAMHDI, the initiative to Link Animal Models to Human DIsease, is designed to accelerate the research process by providing biomedical researchers with a simple, comprehensive Web-based resource to find the best animal models for their research. LAMHDI is funded by the National Institutes of Health under a contract managed by the National Center for Research Resources.

LAMHDI includes mouse data from MGI, the Mouse Genome Informatics website; zebrafish data from ZFIN, the Zebrafish Model Organism Database; rat data from RGD, the Rat Genome Database; yeast data from SGD, the Saccharomyces Genome Database; and fly data from FlyBase.

"LAMHDI gives biomedical researchers access to a simple yet comprehensive Web-based resource that enables scientists to quickly find the best animal models for their research studies," says Harold Watson, Ph.D., the project officer from NCRR’s Division of Comparative Medicine. "Critical tools such as these can help accelerate the research process, ultimately leading us to faster treatments."

LAMDHI is a free, Web-based, resource to help researchers bridge the gap between bench testing and human trials. It provides biomedical researchers with a simple, unbiased resource to find animal models for their research.

The LAMHDI team includes experts in scientific ontology and animal model research from the Washington National Primate Research Center at the University of Washington, the Wisconsin National Primate Research Center at the University of Wisconsin-Madison, and NeuroLex at the University of California, San Diego. TCG, a Washington D.C. project management and application development contractor, leads the initiative.

LAMHDI is operational today, with data being added regularly. Enhancements are planned to let researchers contribute their knowledge of the animal models available through LAMHDI. The LAMHDI goal is to allow researchers to share information about and access to animal models so they can refine research and testing, and reduce or replace the use of animal models where possible.

LAMHDI Database Search

LAMHDI brings together scientifically validated information from various sources to create a composite multi-species database of animal models of human disease. To do this, the LAMHDI database is prepared from a variety of sources.

Some sources are curatorial: The LAMHDI team takes publicly available data from OMIM, NCBI's Entrez Gene database, Homologene, and WikiPathways, and builds a mathematical graph (think of it as a map or a web) that links these data together. We use OMIM to link human diseases with specific human genes. We use Entrez for universal identifiers for each of those genes. We link human genes to their counterpart genes in other species using Homologene, and we link those genes to other genes that are tentatively or authoritatively linked with them in some way using the data in WikiPathways.

This preparatory work gives LAMHDI a web of human diseases linked to specific human genes, orthologous human genes, homologous genes in other species, and both human and non-human genes involved in specific metabolic pathways associated with those diseases.

Some sources provide the model information: LAMHDI includes model data that partners share with us, which is plugged into our data structure. For instance, MGI provides information about mouse models, including a disease for each model, as well as a bit of genetic information (the ID of the model, in fact, identifies one or more genes); while ZFIN provides genetic information for each zebrafish model, but no diseases. We plug each zebrafish model into our database using the genes as the glue. For instance, a hypothetical zebrafish that involves the zebrafish PKD2 gene would plug into the larger disease-gene map at the node representing the zebrafish PKD2 gene, which is connected to the node representing the human PKD2 gene, which in turn is connected to the node representing the human disease known as polycystic kidney disease. (Some of the partner data we receive can even extend our base map. MGI provides a disease for every model, and in some cases this allows us to create a disease-to-gene relationship in our database that might not already be documented in the OMIM dataset.)

With our curatorial and model information in hand, we run a lengthy automated process that exhaustively searches for every possible path between each model and each disease in the data, up to some arbitrary number of hops (producing for each disease-to-model pair a set of links from the disease to the model). The algorithm avoids circular paths and paths that include more than one disease anywhere in the middle of the path. At the end of this phase, LAMHDI has a comprehensive set of paths representing all the disease-to-model relationships in our data, varying in length from one hop to many hops. Each disease-to-model path is essentially a string of nodes in our data, where each node represents a disease, a gene, a linkage between genes (an orthologue, a homologue, or a pathway connection, referred to as a gene cluster or association), or a model. Each node has a human-friendly label, a set of terms and keywords, and — in most cases — a URL linking the node to the data source where it originated. We're now ready for our users.

When a researcher submits a search on the LAMHDI website, LAMHDI searches for the user's search terms in its precomputed list of all known disease-to-model paths (looking for the terms not only in the disease and model nodes, but also every node along each path). The complete set of hits may include multiple paths between any given disease-to-model pair of endpoints. Each of these disease-to-model pair sets is ordered by the number of hops it involves, and the one involving the fewest hops is chosen to represent its respective disease-to-model pair in the search results presented to the user (which are sorted overall by their search term matching scores).

The number of hops is one barometer of the strength of the evidence linking the model and the disease; fewer hops indicates the relationship is stronger, more hops indicates it may be weaker. Note that this indicator works best for comparing models from a single partner dataset: MGI explicitly identifies a disease for each mouse model, so there can be disease-to-model hits for mice that involve just one hop. Because ZFIN does not explicitly identify a disease for each model, no zebrafish model will involve fewer than four hops to the nearest disease: from the zebrafish model to a zebrafish gene to a gene cluster to a human gene to a human disease.

Joining LAMHDI as a Partner Site

Institutions and organizations with databases about animal models of human disease are welcome to join LAMHDI as partner sites. By opening their databases to LAMHDI searches, they can advance health research, allowing scientists to delve deeper into the biologic networks and pathways that define human disease.

To explore joining LAMHDI, contact us at lamdhi-info@lamdhi.org. Detailed information on what LAMHDI needs is in the LAMHDI Partner Starter Kit.

LAMHDI Web Search Seeds

LAMHDI web search seeds (also called "resource seeds" or simply "seeds") are starting pages from which we scan the Internet for appropriate pages for LAMHDI Web Search results. We go to every page that has a link on every starting page, and then to all the pages identified in the referenced pages to find the search term. Our searches thus bring back dozens of hits from each "seed" page.

For your edification, we have created an annotated list of resource seeds. If you know of a site that should be a resource seed, please contact us at lamhdi-info@lamhdi.org.

Accessibility Information

LAMHDI seeks to ensure that our website is accessible to all. If you use special adaptive equipment or software to access the Web and encounter problems when using our site, please let us know. You may write to us at lamhdi-info@lamhdi.org, and we will attempt to provide LAMHDI content to you in a suitable format. Please be as specific as possible when describing the information you seek.

If you need help accessing a PDF document, Adobe® offers conversion tools at its Accessibility Resource Center, http://www.adobe.com/accessibility.

If you are having a problem increasing the font size using Internet Explorer, try the tip at http://newsinhealth.nih.gov/accessibility.htm.

For help with other Microsoft® products, visit their accessibility page at http://www.microsoft.com/enable/.

National Institutes of Health employees who need assistance with accessibility should contact the equal employment opportunity officer in their Institutes.

To learn more about the regulations governing the accessibility of Federal electronic information products, visit the United States Access Board at http://www.access-board.gov/508.htm or the official Section 508 page at http://www.section508.gov/.

—Adapted from the National Institutes of Health website

Privacy Policy

If the information we learn about you from your visit to LAMHDI.org we store only the following: the domain name from which you access the Internet, the type of browser you are using, the date and time you access our site, and the Internet address of the Web site from which you linked to our site. This information is used to measure the number of visitors to the various sections of our site and to help us make our site more useful to visitors. Unless specifically stated otherwise, no additional information will be collected about you.

When inquiries are sent to us by e-mail, we store the question and the e-mail address so that we can respond electronically. Unless otherwise required by statute, we do not identify publicly who sends questions or comments to our Web site. We will not obtain information that will allow us to identify you when you visit our site unless you chose to provide such information to us.

Cookies

While visiting LAMHDI.org you may occasionally encounter a Web page that employs cookies. There are two types of cookies: non-persistent and persistent. A non-persistent cookie is a small file that a Web site transfers to your computer's hard disk to allow our server to remember specific information about your session while you are connected. A persistent cookie is identical to a non-persistent cookie, but includes an expiration date and will "persist" on your computer's hard disk between browser sessions, a feature we use solely to remember your LAMHDI account name between sessions (simplifying your login process).

Requests to send cookies from LAMHDI Web pages are not designed to collect information about you, but only about your browser session or LAMHDI account name. These cookies make it easier for us to provide some of the dynamic features of our site. Non-persistent cookies and the information about your session will be destroyed automatically shortly after you close your browser — they are not permanently stored on your computer or on ours. You must enable the "remember my username" option when logging in before we will set a persistent cookie containing your LAMHDI account name. Unless a LAMHDI Web page specifically notifies you otherwise, we will not collect and maintain personal information about you.

To protect your privacy, be sure to close your browser completely after you have finished conducting business with a Web site that uses cookies. If you are concerned about the potential use of information gathered from your computer by cookies, you can set your browser to prompt you before it accepts a cookie. Most Internet browsers have settings that let you identify and reject cookies.

Questions about LAMHDI privacy policies should be sent to lamhdi-info@lamhdi.org.

—Adapted from the National Institutes of Health website

Copyright

When you access the LAMHDI Web site, you acknowledge that you have read and have agreed to the following terms:

Author and User Rights

  1. Rights to previously copyrighted and licensed content and materials are retained by the original authors.
  2. Information provided to the site by another institution may include their copyright and license notice.
  3. Content and material included on this site is frequently the result of years of research by teams of scientists. Please respect their ownership and interests in these materials and acknowledge them in subsequent references to their work or in subsequent reproductions.
  4. Unless otherwise stated, users of LAMHDI.org are hereby granted a nonexclusive, royalty-free copyright and design patent license to use LAMHDI.org content and material in individual software or documentation.

LAMHDI Rights

  1. By submitting, posting, or displaying content on or through LAMHDI.org, you grant LAMHDI a worldwide, non-exclusive, irrevocable, perpetual, fully sub-licensable, royalty-free license to use, reproduce, translate, create derivative works from, publish, display, and distribute such content (in whole or in part) on LAMHDI.org. LAMHDI is not required to incorporate feedback into any LAMHDI content. LAMHDI reserves the right to syndicate content submitted, posted, or displayed by you on or through LAMHDI.org and use that content in connection with any service offered by LAMHDI.
  2. Unless otherwise stated, all LAMHDI content (excluding data contributed to this site) including all text, images, movies, sounds, data, and software published on www.LAMHDI.org are copyrighted by LAMHDI. Publicly available statistical content that is generated by LAMHDI to monitor and display LAMHDI.org activity is owned by LAMHDI.
  3. COPYRIGHT NOTICE: © Copyright 2010, LAMHDI. All rights reserved.
  4. License is not granted for commercial resale, in whole or in part, of LAMHDI design or content without prior written permission from LAMHDI (lamhdi-info@lamhdi.org).
  5. This material is provided AS IS without express or implied warranty of any kind.

If you do not agree to these terms, you should exit this site now. If you have any questions about these terms, please contact lamhdi-info@lamhdi.org.

—Adapted from the BIRN and SourceForge disclaimers: http://nbirn.net/about/copyright.shtm and http://sourceforge.net/tos/tos.php