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March, 2011

Microsoft Research Connections Blog

The Microsoft Research Connections blog shares stories of collaborations with computer scientists at academic and scientific institutions to advance technical innovations in computing, as well as related events, scholarships, and fellowships.

March, 2011

  • Microsoft Research Connections Blog

    Building a Collaborative Research Relationship with the Chinese Academy of Sciences

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    I recently had the great pleasure of visiting with staff at the Chinese Academy of Sciences (CAS) in Beijing, China. CAS is China's leading academic institution and comprehensive research and development center in natural science, technological science, and high-tech innovation. The Asia-Pacific Microsoft Research Connections team has done a terrific job of establishing a relationship with CAS in recent years. That early groundwork paid off in many ways during my visit to the CAS in February.

    Tony Hey, Corporate Vice President, Microsoft Research Connections presents The Fourth Paradigm: Data-Intensive Scientific Discovery.

    Tony Hey, Corporate Vice President, Microsoft Research Connections presents
    The Fourth Paradigm: Data-Intensive Scientific Discovery.

    There are more than 100 institutes under CAS to focus on specific research areas. I visited the Computer Network Information Center (CNIC), which is a public institution that supports networks and information infrastructure for CAS. Professor Tieniu Tan, deputy secretary of CAS, and some researchers from different research institutes that are involved in the eScience program came to CNIC to host my visit. Among the topics we discussed were eScience-related projects and the Academic Cloud Program at Microsoft Research. I found the CAS team very welcoming and ready to share ideas. We will be building on that enthusiasm: as of February, CAS is a key Microsoft Research Connections partner for eScience in China.

    In addition to meeting one-on-one with CAS high-level staff, leading researchers, and executives, I had the pleasure of delivering my presentation, The Fourth Paradigm: Data-Intensive Scientific Discovery. The audience included a diverse student body as well as faculty representing various research fields, such as chemistry, high-energy physics, biotechnology, geography, environment, database, computing, engineering, and automation.

    Although I was there to speak, I was also there to listen. One of my hosts, Professor Mingqi Chen, director of the Information Department of the CAS General Office, presented on cyber-infrastructure and eScience applications in CAS in three categories:

    The goal of the eScience program in CAS is to build an Open Science Cloud that serves CAS researchers and the broader scientific community. Professor Chen presented some typical eScience applications in CAS, including Galactic Wind Simulation, a real-time prediction of sandstorms system, and ChinaFLUX, which includes a large scientific facility, a field sensor-network real-time data-collection system, and an astronomical virtual laboratory.

    My visit ended on a positive note when another of my hosts, Professor Tieniu Tan, approached me to propose that we further our collaboration through a joint eScience workshop. This workshop will take advantage of the eScience experience and resources that both CAS and Microsoft Research have acquired through our past research work. We will meet again soon to work out the details of this next collaborative venture.

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    Tony Hey, Corporate Vice President, Microsoft Research Connections

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    Coevolution of Viruses and the Immune System Study Featured in Journal of Virology

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    Mosquito larvaeResearchers believe that pathogens are evolving to evade detection from the human immune system. I recently co-published a paper that discussed research into the ongoing evolutionary struggle between the immune system and pathogens. In this study, we sought to identify possible commonalities in HLA (human leukocyte antigen) binding preferences that would reveal patterns of optimization of this component of the immune system in response to the variation in pathogens.

     

    I worked with post-doctoral student Tomer Hertz (now with Fred Hutchinson Cancer Research Lab) and a distinguished group of colleagues from the Institute for Immunology and Infectious Diseases, Royal Perth Hospital, and Murdoch University (Western Australia); the School of Anatomy and Human Biology, Centre for Forensic Science, University of Western Australia (Western Australia); and Fundacion Ciencia para la Vida (Chile).

    Our paper, "Mapping the Landscape of Host-Pathogen Coevolution: HLA Class I Binding and Its Relationship with Evolutionary Conservation in Human and Viral Proteins," appeared in the American Society for Microbiology's Journal of Virology in February 2011. I'd like to share some highlights from the study with you.

    Identifying Possible Commonalities in HLA Binding Preference

    The majority of the cells in our bodies express something called HLA molecules, whose role is to sample cellular proteins and present them on the cellular surface for external surveillance by the specialized cells of our immune systems. This action forces all cells to reveal imprints of their inner workings.

    When something out of the ordinary is detected—for example, the presence of an unusual mutation or a gene expression—the type and quality of the presented samples can spur the immune system's specialized killer cells into action. By sending kill signals to "odd" cells, the immune system can stop diseases such as cancer or viral infections. (Viruses bring their own genetic material to the cell and use the cellular resources to propagate.)

    However, this scrutiny of the immune system creates evolutionary pressure on viruses, which often mutate to evade detection. Since the system of HLA molecules is highly selective in its sampling of protein segments, the mutational patterns in viruses are not entirely random: mutations tend to occur within the segments that HLA molecules are most likely to present.

    On the other hand, over many generations, the distribution of thousands of HLA variants present in human populations may change. Additionally, in different geographic regions, we find significant variation in frequencies of different HLA molecules. This sets up an evolutionary game between the viruses on the one side and our immune systems on the other.

    Targeting Efficiency

    In order to analyze the results of the evolutionary processes that are driven by the interaction of HLA molecules with a wide diversity of viral intruders, we quantified the HLA binding preferences by using a novel measure called "targeting efficiency."

    Targeting efficiency entails capturing the correlation between HLA-peptide binding affinities with the genetic conservation in the targeted proteomic regions. If HLA molecules possessed such targeting efficiency, this would (presumably) prove beneficial to humans. In theory, HLA molecules would draw attention to protein segments that are shared across related viral species as functionally important and thus immutable sections of their proteins. Individual invading viruses would find it more difficult to evade surveillance by mutating, because mutation within these segments would ruin the protein function. Targeting efficiency could even allow the immune system to generalize across related viral species.

    Our analysis of targeting efficiencies for 95 HLA Class I alleles over thousands of human proteins and 52 human viruses indicate that HLA molecules do indeed prefer to target conserved regions in these proteomes! However, the arboviral Flaviviridae (for example, Dengue virus) proved a notable exception in which non-conserved regions were the preferred target of most alleles.

    HLA molecules are encoded in three separate parts of the human genome: A, B, and C. During our study, we discovered that the oldest versions of our HLA molecules—namely the HLA-A alleles and several HLA-B alleles that had maintained a close sequence identity with chimpanzee homologues—were targeting conserved human proteins and DNA viruses (for example, Herpesviridae and Adenoviridae) most efficiently.

    By contrast, the HLA-B alleles were targeting RNA viruses efficiently. This is reminiscent of predator-prey patterns that have been identified in evolutionary theory. For example, we know the following factors to be true:

    • The different HLA families can evolve separately because they are encoded separately.
    • The different HLA families can act on the same targets in the same cells.

    Based on this information, we can extrapolate that evolution is going to drive their binding properties in different directions, thus splitting their targets, as in the established Lotka-Volterra (predator-prey) model of different types of foxes and rabbits inhabiting the same forest. In addition, we identified various patterns of host/pathogen specialization that are consistent with co-evolutionary selection and were also functionally relevant in specific cases. For example, preferential HLA targeting of conserved proteomic regions is associated with improved outcomes in HIV infections as well as protection against Dengue Hemorrhagic Fever.

    I have just scratched the surface of the study in this blog. For complete study details, including a complete presentation of our methodology and findings, please follow the links below.

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    —Nebojsa Jojic, Principal Researcher, Microsoft Research eScience Group

     

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    Computer Science Research Tools Excite Faculty at SIGCSE

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    From March 9-12, a group of Microsoft researchers had their wares on display at SIGCSE 2011, this year's annual convention of the Association for Computing Machinery's Special Interest Group on Computer Science Education (ACM SIGCSE). Held in Dallas, SIGCSE 2011 attracted some 1,200 participants from all over the world, making it the year's biggest computer science education conference.

    SIGCSE 2011

    The passion to develop applications is never more evident than among young people, and educators know they must run to keep up with the latest trends to get the best out of their keen students. It is this sense of urgency that I felt in the halls and venues at SIGCSE, as faculty debated such questions as "What is the next language?" "How can we incorporate parallelism or robotics or gaming?" and "How do we train enough teachers to get enough students to fill the talent pipeline?"

    Standing in the constantly-busy Microsoft booth at SIGCSE 2011, it did seem as if we had a good number of answers. At the .NET Gadgeteer stand, sound, pictures, and robots combined to appeal to people who thought they wouldn't want to be programmers. Fortunately, .NET Gadgeteer will be available to the public mid-year 2011.

    Those visiting Pex4Fun immediately saw it as a means to reach out to students after classes are over, keeping them engaged with coding puzzles. Pex4Fun is available online for free. Many academics recognized the potential of taking the technology to the next ubiquitous platform, mobile devices.  Watch the PEX4FUN Windows Phone 7: A Mobile Game for Programmers video on Channel 9.  

    Another Microsoft demo, Try F#, elicited this from Jan Cuny, director at the National Science Foundation and a staunch advocate for more teachers of computer science at K-12 levels: "In schools and classrooms where the computer platforms are heterogeneous, a browser-based approach is going to help enormously to provide access for all to the new technologies. This solution will be particularly valuable in low-resourced schools where it is difficult to load and maintain a variety of software."

    One of the joys of SIGCSE is bumping into old friends. Doug Blank from Bryn Mawr—who for several years was part of the Institute for Personal Robots in Education (IPRE), introducing robotics to students—now has a system that takes advantage of the dynamic language runtime of Microsoft .NET to bring C#, Python, Ruby, Scheme, and other languages to students so they can write scripts to drive robots, and more. The striking similarities between his system, Pyjama, and Try F# mean that we can learn from each other and connect up again. IPRE participated in the cool, 40-robot Robot Hoedown. Since SIGCSE, Doug informs us that he has added support for F# to Pyjama; as I said—dedicated educators certainly move fast.

    On the last day, the winners of the SIGCSE ACM Student Research Contest, sponsored by Microsoft Research, were announced. Judging from the posters, the standard has certainly risen steadily over the past ten years. Several of the students presented work done as members of teams, but the awards are given for their own individual contribution. In this way, Microsoft encourages collaboration and rewards excellence. It is through collaboration that the strength of Microsoft Research is amplified, and our future is with the faculty of tomorrow.

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    Judith Bishop, Director of Computer Science, Microsoft Research Connections

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