New & Noteworthy
December 12, 2013
The most interesting board games can’t be played right out of the box. You can admire the board and the game pieces, but before the fun can begin you need to spend some time reading the instructions and understanding the strategy.
Gene Ontology (GO) annotations are a little bit like that. You can get interesting information very quickly by just reading the GO terms on the Locus Summary page of your favorite yeast protein in SGD. But if you look deeper and learn just a little bit more about GO, you’ll find that you can get so much more out of it.
A new article by Judith Blake in PLoS Computational Biology is intended to help you do just that. Dr. Blake very succinctly summarizes the most important points in her article, “Ten Quick Tips for Using the Gene Ontology”.
If you’re a molecular or cell biologist, a geneticist, or a computational biologist (or are studying one of those fields), you’re probably already aware of GO. But still, you may be wondering, “Where did these annotations come from? What do those three-letter acronyms mean? How can this help me in my research?” This short and sweet article is a great place to start getting answers to these questions.
We recommend that everyone devote a few minutes to reading this brief article, even if you think you already understand GO. Based on the most frequent questions that we get from researchers who use GO annotations at SGD, we can distill it even further into these top three points as seen from an SGD perspective.
There are people behind these annotations. GO terms are assigned either by real, live humans called biocurators, or computationally using automated methods (each annotation is marked, so you can easily see which is which). At SGD, biocurators are Ph.D. biologists who read the yeast literature and capture experimental results as GO annotations; SGD biocurators are also involved in developing the structure of the GO. We try our best, but like all human beings, we are not infallible. So if you see an annotation that looks wrong or confusing, or if you think an area of the GO could better represent the biology, please contact us (email@example.com) to talk about it. The more expert help we can get, the better the GO and our GO annotations will be.
The details matter. Those three-letter codes that accompany each annotation mean something. Imagine you are deciding how to allocate your lab’s resources and a critical experiment will be based on a particular protein having a particular function. You see a GO annotation for that function and that protein, so you’re good to go! But wait a minute…
Those codes tell you the experimental evidence behind the assignment of a GO term to a gene product. If that annotation has an IDA (Inferred from Direct Assay) evidence code, then the function was shown in an actual experiment, so you probably are good to go. On the other hand, if the annotation has an ISS (Inferred from Sequence Similarity) evidence code, then it was made solely based on resemblance to another protein. This is still valuable information, but you might not want to bet the farm (or the lab) on it.
Dates are very important too. Both the annotations and the GO itself are constantly updated to keep up with new biological knowledge. Because of this, everything related to GO – from a single annotation shown on an SGD GO Details page, to the downloadable files that contain all GO annotations or the ontology itself – is associated with the date it was created. So if you do any analysis using GO annotations it’s important to note the dates of both the annotation and ontology files that you used. This is especially important if you repeat a GO term enrichment for a gene set over time. The results will definitely change, as significant enrichments become more strongly supported while marginally significant enrichments may not be reproduced.
Go deeper. GO is not just a list of terms. GO terms have defined relationships to each other, with some being broader (parent terms) and some more specific (child terms). If you really understand the structure of GO, you’ll be able to make much better use of the annotations.
For example, if you look for gene products in SGD annotated to the GO term “mitochondrion,” you’ll currently find 1055 of them1. Does that mean that there are exactly 1055 proteins or noncoding RNAs known to be in yeast mitochondria? Noooo!
There are more than that, because the term “mitochondrion” has more specific child terms such as “mitochondrial matrix”; some proteins are annotated directly to those terms and not to the parent term. If you had used the original list of proteins annotated to “mitochondrion”, you’d be missing 92 gene products2 that are so well-studied that their precise locations in the organelle are known! The structure of the GO allows you to gather all the gene products annotated to a term and to all its child terms (YeastMine has a template tailored to this kind of query).
As you can tell, there is a lot more to GO annotations than a lot of people think. And as you dig deeper, you begin to be able to use them in ever more sophisticated ways. Sort of like the natural progression with a strategy board game like Settlers of Catan. At first, even after reading the instructions, you are just trying to work through the game. But as you play more and more, you quickly learn where to build your roads, which islands to colonize and so much more. So get out there and master GO. You’ll be glad you did.
1As of December 2013, using YeastMine template “GO Term -> All genes” (includes Manually curated and High-throughput annotation types).
2As of December 2013, using YeastMine template “GO Term Name [and children of this term] -> All genes” (filtered to exclude Computational annotation type so that only Manually curated and High-throughput annotation types are included).
November 25, 2013
Stanford offers an innovative class, targeted at sophomore undergraduates, where students use yeast to determine how a mutation in the p53 gene affects the activity of the resulting p53 protein. What makes this class even cooler is that the p53 mutants come from actual human tumors—the undergraduates are figuring out what actual cancer mutations are doing! And the class uses what we think is the most important organism in the world, S. cerevisiae.
To learn more about the course, we decided to interview Jamie Imam, one of the instructors. After reading the interview, you will almost certainly be as excited about this class as we were and it may even get you to wishing that you could teach the class at your institution. With a little help, you can.
The creators of the course, Tim Stearns and Martha Cyert, really want as many people as possible to use this class to teach undergraduates about what real science is and how fun and exciting it can be. To that end, they are happy to help you replicate the course wherever you are. If you are interested, please contact Tim and/or Martha. You’ll be happy you did. Their contact information can be found at the Stearns lab and Cyert lab websites.
Here now is the interview with Jamie. What a great way to get undergraduates excited about the scientific process.
Can you describe the class?
Sure. Bio44X is designed to be similar to an authentic research experience or as close to one as you can replicate in the classroom. During the quarter, students study mutant versions of a gene called p53, a tumor suppressor that is frequently mutated in cancer. Each partner pair in a classroom gets one p53 mutant that has been identified in a human tumor to study in our yeast system. Throughout the course of the 10 weeks, the students study the transactivation ability of their mutant compared to the wild-type version, and then work to figure out what exactly is wrong with the mutant (Can it bind DNA?, Does it localize to the nucleus properly?, etc.). Multiple sections of this course are taught during the Fall and Winter quarters, so several pairs end up studying the same mutant. We bring these students together to discuss and combine their data throughout the quarter, so there is a lot of collaboration involved. I think the students really enjoy having one topic to study in depth over the quarter rather than short individual modules, and the fact that we are studying a gene so important in cancer makes it easier to get them to care about the work they are doing.
Tell me a little bit about how this class was started.
Previously, Bio44X at Stanford was the more traditional “cookbook” type lab course. Every 2 weeks, the topic would change and students would work through set protocols that had a known correct answer. In 2010, Professors Martha Cyert and Tim Stearns set out to design and pilot a research-based course on a medically relevant topic (the tumor suppressor p53) in response to some national calls for biology lab course reform. Two years and many changes later, the new research-based lab course replaced the previous version and is now taken by all of the students that need an introductory lab course in Biology.
What kinds of experiments do the students get to do in the class?
Students get exposed to a variety of lab techniques that can be used beyond our classroom. We start with sterile technique and pipetting during the very first week (some students have never pipetted before!). During the first class, the students also spot out some yeast strains so they can start collecting data on the transactivation ability of their p53 mutant right away. Once they have some basic information about the function of their mutant, the students then extract protein from their yeast strains. Throughout the rest of the quarter, students use this protein to conduct a kinetic assay, Western blot, and assess DNA binding ability of their mutant p53. They also get some exposure to fluorescence microscopy when they use a GFP-tagged version of their mutant to determine whether it can localize properly to the nucleus. But the most important thing of all is that students learn how to analyze the data and think critically about it. Not only do they “crunch the numbers” but they must use that information to draw some actual conclusions about what is wrong with their mutant by the end of the quarter.
How hard is it to set up and run the class?
It takes a lot of organization because we have around 200 or more students that take this class every year! Fortunately, we have a great team to help organize the setup of the labs so that the instructors can focus on the teaching. Nicole Bradon manages a small staff that sets up the classrooms and prepares all of the reagents for the lab each week. Dr. Daria Hekmat-Scafe, who is one of the instructors, constructs many of the yeast strains that we give to the students. The team of lecturers (Dr. Shyamala Malladi, Dr. Daria Hekmat-Scafe and I) all work together on lectures and other course materials so everyone gets a similar experience. All together, it takes a lot of behind-the-scenes work, but then the students really get to focus on the experiments and their results.
Do you enjoy teaching the class? What is your favorite part? Your least favorite part?
I love teaching this class! It is so fun to go through this research experience with so many students and they all bring their unique perspectives to the course (we get engineers, psych majors, bio majors, econ majors and others). Also, each section has only 20 students so you really get the chance to get to know them over the course of the 10 weeks. Sometimes the experiments don’t work as planned (like real science) but overall it ends up being a great learning experience.
What do you hope the students will learn and get out of the class? And are they learning/getting it?
We hope that students learn to think critically and what it really means to “think like a scientist”. Too often, science is boiled down to a series of facts that students are expected to memorize and that isn’t what science really is! Science is all about finding exciting questions and constructing experiments that try and answer those questions. The beauty of a research-based lab course is that students can also feel more in charge of their own learning. We have performed assessments of the class and have found that over the course of the quarter, students develop a more sophisticated understanding of what it means to “think like a scientist” and a large portion are more interested in becoming involved in scientific research. I think this is great, as I feel that undergraduate research helped me understand science so much more deeply than many of the courses I had taken.
How would someone at another University go about replicating this course? Are there resources available to help them get started and/or keep it running?
Our group is willing to share our course materials and knowledge with others that are interested in replicating this at other institutions. Anyone who is interested should feel free to contact us! Also, there is a paper in preparation that will describe some of the key aspects of the course as well as more details about what we have learned from the assessments of the course over the past few years.
There you have it…a great class that uses the awesomeness of yeast to teach undergraduates how to think like scientists. Again, if you’re interested in learning more, please contact Tim Stearns and/or Martha Cyert at Stanford.
November 3, 2013
Wish you were going to Cold Spring Harbor for the Cell Biology of Yeasts meeting this week, November 5-9? SGD will be live tweeting from CSHL, highlighting topics from talks and posters. Keep up with events at the meeting by following @yeastgenome on Twitter or searching #YCB2013 for all tweets!
October 23, 2013
A memorial gathering in memory of Fred Sherman will be held at 10:00 am on Friday, December 6, 2013. The gathering will be held in the Ryan Case Methods Room (Rm #1-9576) of the University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester NY 14642. This event will be a celebration of the life and science of Fred, comprised of reminiscences about Fred by some who knew him well, followed by an opportunity for any guest to say a few words about Fred. For more information, contact Mark Dumont (Mark_Dumont@urmc.rochester.edu), Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642 (Phone 585-275-2466).
October 7, 2013
Congratulations to Randy Schekman, James Rothman, and Thomas Südhof, who have been awarded the 2013 Nobel Prize in Physiology or Medicine for their work in understanding how the cell organizes its transport system. Randy Schekman used the awesome power of yeast to identify and characterize genes required for vesicle traffic. James Rothman characterized these and other proteins in mammalian cells, and Thomas Südhof showed the critical role of vesicle trafficking in nerve cells. You can read summaries of their Nobel winning work at Nature, The Scientist, and The New York Times, or search SGD to see how each of these researchers has used our model organism in their research: Randy Schekman, James Rothman, Thomas Südhof.