iHOP - Information Hyperlinked over Proteins

A network of concurring genes and proteins extends through the scientific literature touching on phenotypes, pathologies and gene function.
iHOP provides this network as a natural way of accessing millions of PubMed abstracts. By using genes and proteins as hyperlinks between sentences and abstracts, the information in PubMed can be converted into one navigable resource, bringing all advantages of the internet to scientific literature research.

Terms of Use
iHOP was developed and created by Robert Hoffmann and is a free service from the academic domain, licenced under a Creative Commons Attribution-No Derivative Works 3.0 License. Hopefully you will find that iHOP makes things possible which would not be without it. iHOP is free of charge, thus its continuity will depend on the community it was created for.

a) Please cite the use of iHOP in your work as:
- A Gene Network for Navigating the Literature. Hoffmann, R., Valencia, A. Nature Genetics 36, 664 (2004) and
- iHOP - http://www.ihop-net.org/

b) Electronic services, which are based on iHOP data, must provide credit and links to the iHOP server (http://www.ihop-net.org) visible to all users whenever iHOP data is displayed in its original or a derivate form.

c) Bulk downloads.
Please note that iHOP is a freely available tool from the academic domain. Not a company! Thus, it is necessary to limit server load and to give preference to individual users. Bulk downloads may lead to the banning of IP addresses for specific servers or institutions!
Please contact directly with Robert Hoffmann if there should be a scientific reason for bulk downloads. Thank you for your cooperation!

Entry point to the network
Typically one is interested in information on a specific gene or protein - the entry point to the literature network. Simply type a synonym (e.g. SNF1) or an accession number (e.g. UniProt or NCBI Gene, etc.) into the search field in the menu bar or the main page.

To make your search more stringent, you can specify a specific search field or organism. Tip: Start off with few search terms (e.g. use "ABC" instead of "ABC protein")

In many cases your search term will correspond to various genes or proteins. Click on one of the icons on the right-hand side to select the corresponding gene:
Each icon corresponds to a specific view on a gene. Please note that not all views will be available for all genes, since this is dependent on the available literature information.

Different views on a gene
Minimal information

The minimal information view contains general information, like the symbol, name and organism of a gene. Moreover it provides:
- Useful links to external resources (e.g. UniProt, NCBI, OMIM, etc.)
- Links to other iHOP views on this gene
- Homologues
- Enhanced PubMed/Google query

Interaction information

This view contains all sentences found in the literature for the main gene of a page (gene A) and other genes (gene B). Gen symbols within sentences are hyperlinked. Therefore, clicking on a gene symbol (e.g. gene B) will bring you to the page of gene B.
Besides literature information, these pages contain also interactions collected from external resources (e.g. large scale experimental data). Read more.

Defining information

This view contains all sentences found in the literature that mention the main gene (gene X) together with relevant biomedical terms (e.g. lymphoma).
Sentences are ranked by significance, so that screening over a few sentences will be usually sufficient to gain an idea of a gene's function.

Click on the icon beside sentences to read the corresponding abstracts or full text papers. Interesting sentences can be collected into a Gene model by clicking on the icon. Read more.

Navigation trail - from gene to gene
In iHOP standard internet navigation is maintained. For example, when analyzing sentences for gene A, you might come across an interesting or unexpected association with gene B. The sentence found will mention one aspect of the relationship between A and B, but not necessarily the most important one. By clicking on the synonym of gene B, however, its corresponding page will be shown, and all sentences associating A and B will be ranked first, since you arrived at gene B from gene A.

Synonyms for the previous main gene will be shown in purple (e.g. gene A).

Filter and options
Use the Filter and Options link in the menu bar to change overall appearance parameters.
- Show official symbols Select this option to show the official gene symbol beside the identified synonym; e.g. PC7 -> [PCSK7] PC7
- Show PMID instead of abstract icon
- Sort sentences by articles

Change settings here...

Synonym ambiguity
Many gene or protein synonyms are ambiguous, thus one and the same synonym is often used for different genes. Even human experts can have difficulties to resolve such ambiguities and automatic systems, like iHOP, will therefore always exhibit certain errors.
However, iHOP has the advantage over purely graphical representations in that researchers can keep permanent control over the origin and reliability of information, since they move between sentences starting from the original source.
In many cases, experts will recognize incorrectly identified symbols simply by scanning a sentence.

iHOP confidence value - Facilitating the identification of ambigous genes
Although no definite solution for the problem of synonym ambiguity is in sight, it is possible to put an automatically derived confidence value to specific gene references. This iHOP confidence value is illustrated through the colour intensity of a star: .
Please note: The absence of a star does not mean that a certain term could not be a gene, but simply that supporting evidence is not available.

Gene Model - the logbook
In the course of navigation through iHOP, interesting sentences can be added to the Gene Model by clicking on the icon beside a sentence. The Gene Model stores these sentences and represents the results of your investigation. Furthermore, all the associations between collected sentences are represented as a graph.
e.g.
Nodes in this graph represent genes. Edges correspond to sentences that associate two genes with each other.

Exploring the model - The model graph makes it possible to analyze your collection of sentences in an interactive manner and to get familiar with the newly aquainted knowledge.
By clicking on a gene, all its synonyms will be highlighted in red and the corresponding sentences will be ranked to the top. By clicking on an edge, those sentences containing the connected genes are shown at the top. Furthermore, a line separates these highlighted sentences from all others.
Extending the model - By clicking on a gene in a sentence, the corresponding information page for the gene will be opened and additional information can be added to the Gene Model.

Large-scale data
Recently large scale experiments have provided new insights into the complex protein interaction networks within the cell. However, this increase in information comes at the cost of lowered quality and the manual evaluation through experts remains indispensable.
Manual evaluation usually includes the comparison with existing knowledge from the literature. In practice this involves jumping back and forth between the experimental data and free text searches in PubMed. iHOP allows the user to overlay experimental data on the literature network, so that sentences that include proteins whose interaction has experimental evidence will be highlighted and ranked first.
Use the Filter and options menu to include or exclude specific experimental data sets. Click here for an example gene with experimental evidence from large-scale screens.

Enhanced PubMed/Google query
Each gene page contains a link to execute an Enhanced PubMed/Google query at the top. These queries allow you to quickly query PubMed or Google for a specific gene including all its synonyms and orthographic variations.


References
A Gene Network for Navigating the Literature. Hoffmann, R., Valencia, A. Nature Genetics 36, 664 (2004)
Implementing the iHOP concept for navigation of biomedical literature. Hoffmann, R., Valencia, A. Bioinformatics 21(suppl. 2), ii252-ii258 (2005).

iHOP for developers and Service Provider
Click here for detailed information on how to link to iHOP or integrate iHOP content in your website.

Contact
If you have questions or comments, please write to Robert Hoffmann.