Keynote Speakers: Stanley Nelson and Isaac Kohane

PSB 2010

Stanley Nelson Stanley Nelson
Professor of Human Genetics and Psychiatry
David Geffen School of Medicine at UCLA

Tuesday, January 5 11:30-12:30pm in Salon 2&3

Whole human cancer genome sequencing: issues and progress towards common application

Cancer is at its heart a genetic disease. Understanding comprehensively the spectrum of point mutations, insertion/deletion mutations, chromosomal losses/gains, and translocations that have occured in individual cancers provides immense insight into the basis of cancer genesis and resistance to therapy. The tools of modern genomics now open up the possibility of routine application of whole genome resequencing to the goal of identification of the complete spectrum of mutations that have occured in individual cancers. The talk will describe 1) the current methods of shotgun whole genome mate paired sequencing, 2) progress in alignment methods of the billions of reads that is the engine behind variant detection, 3) demonstration of whole human genome sequencing and assessment of coverage/accuracy, 4) special issues related to cancer samples, 5) a roadmap towards sub $10,000 genomes that is readily attainable. All of these tools will be available to many genomic laboratories and not restricted to genome centers.

Stanley F. Nelson is Professor of Human Genetics and Psychiatry within the David Geffen School of Medicine at the University of California, Los Angeles. He received a BS degree from the University of Michigan in Physics in 1982. He graduated from Duke University School of Medicine in 1987 and completed an ITT International Fellowship to Sweden in the Laboratory of George Klein. He has trained in Pediatrics and Pediatric Hematology-Oncology at UCSF School of Medicine, and subsequently trained as a postdoctoral fellow with Patrick Brown at Stanford University from 1990-1993 where he developed genomic mismatch scanning and initiated the development of DNA microarrays. He currently leads a research group using genomic approaches to identify genetic variation contributing to both common-complex and rare human disorders. He is particularly interested in using broad genomic approaches to search for genetic mutations that will ultimately provide a catalogue of the set of genetic perturbations that can lead to the development of cancer and neurodevelopmental disorders, and has published over 120 papers in these areas. His laboratory uses and develops methods in relation to massively parallel sequencing, high density DNA genotyping, and microarray based gene expression analysis. Along with collaborators in the Neurobehavioral Genetics Program, his laboratory has published genome-wide significant linkage evidence in autism and ADHD, as well as common allele associations in both disorders in both the Finnish and US populations. The laboratory is developing analytical approaches to the identification of key genes involved in glioma development, which are relevant to all cancers. Within this project, the laboratory has developed a gene expression based classifier of high grade gliomas which has been subsequently validated from other researchers, and is now being mined for specific mutational events that contribute to gliomagenesis. His laboratory has developed methods of identifying identical by descent DNA intervals and assessing the association of genes with specific traits using genome-wide DNA arrays. These tools are being applied to over 12 different developmental disorders to identify linkage including a collaborative study with on the identification of novel risk alleles for breast cancer. Most recently, his laboratory has developed a powerful and efficient short sequence aligner that is tolerant of differences with the consensus genome to use to identify point mutations, small and large indels throughout the cancer genome. Using the developed techniques the laboratory has reduced the cost of whole human genome shotgun resequencing to under $30,000 and improved the ability to detect variants reliably. Further improvements in image processing promise to make human genome sequence a routine process for disease gene identification.

Isaac Kohane Isaac Kohane
Professor of Pediatrics and Medicine, Harvard Medical School

Wednesday, January 6 7:30-9pm in Salon 2&3

Preventing the Incidentalome and Practicing a Responsible Personalized Medicine

The promise of genomic medicine includes personalizing diagnoses and therapies, if not to the level of the individual, then to a small population of individuals with shared pathophysiology. The availability of commodity-priced genome-scale assays has led to increased popular demand and expectation for the application of these assays to clinical care. Yet there are several structural impediments to the safe practice of genomic medicine, all of which fall within the domain of biomedical informatics. These include A) the growth of the Incidentalome, the tsunami of false positives that inevitably result from application of massively parallel tests, B) the lack of systematic interpretations of genomic tests and evaluation of their performance. C) The absence of a mechanism to transfer the growing knowledge of genomics to the physician at the point of care. D) The increasingly blurry line between clinical research and clinical care. Fortunately there are several developments in biomedical informatics that address these impediments. Foremost among these is the movement to treat subjects as full and autonomous partners in research collaborations even as they continue to be treated as patients and secondarily the industrialization of phenotyping and sample acquisition methodologies to match the efficiencies of genome-scale measurements. I will review both the challenges and leading exemplars of the solutions brought to bear.

Isaac (Zak) Kohane is the director of the Children's Hospital Informatics Program and is the Henderson Professor of Pediatrics and Health Sciences and Technology at Harvard Medical School (HMS). He is also the co-Director of the HMS Center for Biomedical Library and Director of the HMS Countway Library of Medicine. Dr. Kohane leads multiple collaborations at Harvard Medical School and its hospital affiliates in the use of genomics and computer science to study diseases (particularly cancer and autism) through the perspective of biological development. He also has developed several computer systems to allow multiple hospital systems to be used as "living laboratories" to study the genetic basis of disease while preserving patient privacy. Among these, the i2b2 (Informatics for Integrating Biology and the Bedside) National Computing Center has been deployed at over 18 academic health centers internationally.

Dr. Kohane has published over 160 papers in the medical literature and authored a widely used book on Microarrays for an Integrative Genomics. He has been elected to multiple honor societies including the American Society for Clinical Investigation and the American College of Medical Informatics. He leads a doctoral program in genomics and bioinformatics at the Division of Health Sciences and Technology at Harvard and MIT. He is also a practicing pediatric endocrinologist and father of three energetic children.

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