Brown University Center for Computational Molecular Biology


CCMB Distinguished Technology Lecture Series 2006-2007

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Steve Lincoln
Vice President of Informatics Affymetrix Inc.

Whole genome association studies:
Success stories and lessons for the future

Whole genome association studies have recently become practical, both through the invention of new cost-effective genotyping technologies, and through the recent understanding of linkage disequilibrium patterns in various human populations. For example, Affymetrix GeneChip Microarrays typing 500,000 Single Nucleotide Polymorphisms have now been used to characterize loci involved in diabetes, autism, individualized drug responses, and other phenotypes of significant medical interest. Through these studies, new software tools and best practices are emerging to help with the management, quality control and analysis of these large genetic data sets. Of course, these tools become increasingly critical as even newer GeneChip technologies emerge, accessing almost a million SNPs and also providing genome-wide analysis of Copy Number Variants. We will review these new laboratory technologies and some of the computational implications of the data they produce, with a eye to the current best practices now evolving in the field. With this understanding, new research opportunities in methods and software development have become more clearly defined.

Wednesday, April 4th, 2007
CIT Bldg, Room 241, SWIG Boardroom

Dr. Shaw is the chief scientist of D. E. Shaw Research and a senior research fellow at the Center for Computational Biology and Bioinformatics at Columbia University. He and his research group are currently involved in the design of massively parallel machine architectures and algorithms for high-speed molecular dynamics simulations, and in the use of such simulations to study biomolecular systems of interest from both a scientific and a pharmaceutical perspective.
Symposium's page

David E. Shaw
Chief Scientist, D. E. Shaw Research;
Center for Computational Biology and Bioinformatics, Columbia University

New Architectures for a New Biology

Some of the most important outstanding questions in the fields of biology, chemistry, and medicine remain unsolved as a result of our limited understanding of the structure, behavior and interaction of biologically significant molecules. The laws of physics that determine the form and function of these biomolecules are well understood. Current technology, however, does not allow us to simulate the effect of these laws with sufficient accuracy, and for a sufficient period of time, to answer many of the questions that biologists, biochemists, and biomedical researchers are most anxious to answer. This talk will describe the current state of the art in biomolecular simulation and explore the potential role of high-performance computing technologies in extending current capabilities. Efforts within our own lab to develop novel architectures and algorithms to accelerate molecular dynamics simulations by several orders of magnitude will be described, along with work by other researchers pursuing alternative approaches. If such efforts ultimately prove successful, one might imagine the emergence of an entirely new paradigm in which computational experiments take their place alongside those conducted in "wet" laboratories as central tools in the quest to understand living organisms at a molecular level, and to develop safe, effective, precisely targeted medicines capable of relieving suffering and saving human lives.

December 7th

Dr. David L Barker is Vice President and Chief Scientific Officer at Illumina, Inc., in San Diego, California. Dr. Barker served from 1998 to 2000 as Vice President and Chief Science Advisor at Amersham Biosciences, now part of General Electric. From 1988 to 1998, Dr. Barker held senior positions, including Vice President of Research and Business Development, at Molecular Dynamics, Inc., until the acquisition of Molecular Dynamics by Amersham. He serves on the Boards of Directors of Excellin Life Sciences Inc., Cell Biosciences, and Microchip Biotechnologies, Inc. In his academic career, Dr. Barker conducted interdisciplinary research in neurobiology as a postdoctoral fellow at Harvard Medical School, Assistant Professor at the University of Oregon and Associate Professor at Oregon State University. Dr. Barker holds a BS with honors in Chemistry from the California Institute of Technology and a PhD in Biochemistry from Brandeis University.
Symposium's page

David Barker
Vice President and Chief Scientific Officer Illumina, Inc.

Capturing Common Variation
in the Human Genome on a Single Microarray

The International HapMap Project provided a framework for accessing all common variation in the human genome through SNP genotyping. The development of the Infinium® Assay has enabled true whole genome genotyping: One can now genotype more than 650,000 SNPs on a single microarray, enough to capture essentially all common human variation, at a cost per SNP three orders of magnitude less than six years ago. This methodology is being used by researchers around the world to genotype tens of thousands of patient samples in efforts to discover the genetic basis of common diseases such as cancers, heart disease, arthritis, and diabetes. Detailed scrutiny of many human genomes has revealed that both large and small deletions of genomic sequence are surprisingly frequent in "normal" genomes, and are commonplace in cancer cells. These variations can also be analyzed by SNP genotyping using appropriate software tools. The avalanche of data generated by whole genome genotyping presents challenges for computational biology, as valid associations to disease-causing genes are hidden among literally billions of data points generated by each study. In addition, further understanding will require the integration of genomic, epigenetic, and gene expression data by computational tools that reveal underlying mechanisms.

December 6th

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