New & Noteworthy

Explore a Large New Chemogenomics Dataset Via SGD

March 26, 2014

What happens when you cross two comprehensive deletion mutant collections with a library of more than 1800 structurally diverse chemicals? HIP HOP happens. Not the music, but a whole lot of very informative phenotype data – over 40 million data points!

The response of S. cerevisiae mutant strains to a chemical can tell us a lot about which pathways or processes the chemical affects. This is not only interesting for yeast biologists, but also has important implications for human molecular biology and disease research. So a group at The Novartis Institutes of Biomedical Research decided to test the sensitivity of nearly 6,000 mutant yeast strains to a panel of about 1,800 compounds. 

Hoepfner and colleagues have published these results and have also generously offered them to SGD.  They used the HIP and HOP methods (HIP, HaploInsufficiency Profiling, using diploid heterozygous deletion mutant strains; HOP, HOmozygous deletion Profiling, using diploid homozygous deletion mutant strains) that have proven very useful in yeast since the creation of the systematic deletion mutant collections.

To do this mammoth series of experiments they obviously needed to set up an automated pipeline. These sorts of experiments have been done before, but in this study Hoepfner et al. improved on existing procedures in many ways: the physical techniques, the controls and replicates included, and the methods for data analysis.

Phenotype annotations in SGD. We’ve incorporated a subset of these results into SGD as mutant phenotype annotations. Why a subset? Some of the chemicals that were used in these experiments are un-named proprietary compounds, so the individual phenotypes would not be very informative in the context of SGD. We’ve added the phenotypes that involve named chemicals to SGD – more than 5,500 annotations. These may be viewed on Phenotype Details pages for individual genes (see example), retrieved as a set using Yeastmine, or downloaded along with all SGD mutant phenotype annotations in our phenotype data download file.

Easy access to the full dataset and analyses. We’ve also added a new set of links to SGD that take you directly from your favorite gene to the authors’ website, which provides full access to all of the data and interesting ways to look at it (see below). When you click on a “HIP HOP Profile” link from the Locus Summary page or the Phenotype Details page of a gene in SGD, the landing page at the authors’ website allows you to explore data for mutants in that gene or for chemicals affecting that mutant strain. You can see which chemicals had the greatest effects, which other mutant strains have a similar range of phenotypes, and much more. And if a chemical that has interesting effects is proprietary, don’t worry; Hoepfner and colleagues have stated that they “encourage future academic collaborations around individual compounds used in this study.”

Information about mutant strains. In the course of this study, the authors also generated some very useful data about particular mutant strains in the deletion collection. Some of them were hypersensitive to more than 100 different chemicals. Others turned out to be carrying additional background mutations that could affect the phenotypes of the mutant strain. We are planning to display this kind of information (from this and other studies) directly on SGD Phenotype Details pages in the future.

We thank Dominic Hoepfner and colleagues for sharing these data with SGD and for helping us to incorporate the data.  And we encourage you to explore this new resource and contact us with any questions or suggestions.

Links from SGD lead to multiple ways of exploring the full chemogenomics dataset.