MORPHIN: a web tool for human disease research by projecting model organism biology onto a human integrated gene network.

If you missed it, there was another headline reporting the discovery of a new potential gene target, “CREB3L3 May Be Target for Obesity, Diabetes Treatments” that has shown promise in mice anyway. In light of all these new disease-related genes being discovered daily–in various model organisms–wouldn’t it be awesome if there was a tool that allowed us see how new genes discovered in model organisms linked to human disease? This may seem like a strange thing to do considering the fact that researchers use model organisms in order to study human diseases in the first place. After all, one would expect that the genes discovered in a model organism whilst conducting research on a particular disease should link to the disease being modeled, right? Of course! But what if the gene you discover while researching angina actually plays a big role in erectile dysfunction? What if the gene you’re targeting for erectile dysfunction may actually play an important role in muscular dystrophy? While Viagra was originally developed to treat angina by targeting phosphodiesterase 5, it became a blockbuster treatment for erectile dysfunction. Similarly, Cialis which was developed also targeting PDE5 for erectile dysfunction has been explored for the treatment of Beckman’s muscular dystrophy.

Research behind the little blue pill started with angina. By Tim.Reckmann (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)%5D, via Wikimedia Commons

The point is…maybe you’ve uncovered a group of genes that may be the key to a disease you’re studying, but there may be other disease indications you may want to consider branching off and studying in the future. And now, there’s a tool to help with that: Enter MORPHIN

I tested MORPHIN using the gene from the aforementioned article: CREB3L3, along with another gene that has been hyped as a target for curing obesity: Leptin (LEP) and the Leptin receptor (LEPR). I entered the three genes, selected ‘mouse’ for the model, and submitted the query.

Unfortunately, MORPHIN is very slow. A query can take 3-5 min, even 20 min if there’s a queue. I’m guessing the delays stems from using not an overlap-based gene set association measure (Fisher exact test) in addition to a network-based gene set association measure, RIDDLE to enhance the sensitivity of association mapping. RIDDLE itself takes 2-3 min to run if you’re lucky. I’m sure the mapping of queried animal genes to human orthologs is the fastest part considering there are really fast services already available like http://mygene.info.

35 min later, we have the result! (MORPHIN must be really popular!). Of course, the first disease that was associated with these three genes was ‘Eating disorders.’ The second one was ‘HELLP syndrome’. A quick search in pubmed reveals that there are 2000+ articles on HELLP syndrome, four of which are linked to Leptin, none to CREB3L3. Interesting. Might be fun to try and see how the results of a query for various phosphodiesterases, but I don’t think I can spare another hour on this.

If you’re curious, see the development time line of Viagra here.

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