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7:00 am Registration Open

Sponsored by
febit (New Logo)
7:30 Breakfast Presentation

The Power to Detect: HybSelect™ for Targeted Sequence Capture

Jack Leonard, Ph.D., Vice President of Technology Commercialization, febit, Inc.

Certain “high value” regions of the genome have been associated with certain disease states, phenotypic traits, responses to drug treatment or other environmental stimuli. Targeted re-sequencing of genomes can identify variants faster and at a much lower cost than whole genome sequencing. Genomic hot-spots ranging between tens and thousands of kilobases are excellent targets for HybSelect™, a new automated microfluidic solution for sequence-specific capture from febit. Integrated HybSelect™ automation allows walk-away convenience and only requires 30 minutes of hands on time, offering the simplest targeted sequence capture method available.


8:15 Chairperson’s Remarks
Patrice Milos, Ph.D., VP & CSO, Helicose Biosciences


Novel Genetic Alphabets for Genome Sequence Analysis in Complex Biological Environments

Steven A. Benner, Ph.D., Distinguished Fellow, Foundation for Applied Molecular Evolution (FAME)

The Foundation for Applied Molecular Evolution artificially expanded genetic information systems, self-avoiding molecular recognition systems, and reversible terminators in combination support novel architectures to detect disease-related genetic variation in biologically complex environments, such as sputum, urine, and feces. This talk will review these, as well as mutant enzymes that accept them, to support single-plexed and multiplexed detection of specific sequence variants in these samples.

8:50 Amplification of Genomic DNA from Small Samples and Single Cells Using MDA

Roger Lasken, Ph.D., Professor, Microbial Genomics, J. Craig Venter Institute

The MDA reaction can be used to amplify DNA from minute specimens for use in PCR and other nucleic acid detection and analysis methods. This simple isothermal reaction serves both DNA sample preparation and improvement of sensitivity where DNA template is limiting. Examples are discussed using environmental samples such as soil and clinical specimens containing human or bacterial DNA. Amplification from single bacterial cells provides sufficient DNA for genomic sequencing without the need to develop culture methods. This approach has provided genomic sequences for previously inaccessible uncultured microbes.

9:20 Issues in Sequence-Based Association Studies Leveraging Next-Generation Technologies

Ashley Scott, Ph.D., Postdoctoral Researcher, Scripps Translational Research Institute

The availability of efficient high-throughput DNA sequencing technologies has paved the way for genetic association studies that leverage not only genotype information at pre-specified loci, but exhaustive DNA sequence variation characterization on the subjects in a study as well. The design and analysis of studies that take advantage of exhaustive sequence data are not trivial and raise questions about the power of various sampling schemes for such studies, the need for reliable capture technologies in the face of quesitons about the appropriateness of genome-wide vs. candidate gene approaches, reliable nucleotide assignment strategies, and, importantly, sophisticated and integrated data analysis methods. We discuss these issues in the context of a large-scale association study that we are pursuing investigating the genetic basis of anorexia.

Sponsored by
Rain Dance

9:50 Enrichment of Resequencing Targets for Analysis of Rare Variants
Lin Pham, Ph.D., Commercial Application Scientist, RainDance Technologies, Inc. 

10:05 Networking Coffee Break, Exhibit & Poster Viewing




Evaluation of Next Generation Sequencing Platforms for Population Targeted Sequencing Studies

Samuel Levy, Ph.D., Translational Genomics, Scripps Translational Science Institute

11:15 High-Throughput Sequencing in Mice: A Platform Comparison Identifies a Preponderance of Cryptic SNPs

Kari J. Buck, Ph.D., Professor, Department of Behavioral Neuroscience, Oregon Health & Science University; Research Scientist,
VA Medical Center

We sequenced the two most commonly used inbred mouse strains, DBA/2J and C57BL/6J, across a region of chromosome 1 (171.6 – 174.6 megabases) using Applied Biosystems (SOLiD) and Illumina (Genome Analyzer). Using the same templates on both platforms, we compared realignments and single nucleotide polymorphism (SNP) detection with an 80 fold average read depth across platforms and samples. While public datasets currently annotate 4,527 SNPs between the two strains in this interval, thorough high-throughput sequencing identified a total of 11,824 SNPs in the interval, including 7,663 new SNPs. Furthermore, we confirmed 40 missense SNPs and discovered 36 new missense SNPs. We conclude that comparisons utilizing even two of the best characterized mouse genetic models, DBA/2J and C57BL/6J, indicate that more than half of naturally-occurring SNPs remain cryptic.

11:45 Translating Next-Generation Sequencing into the Clinical Diagnostic Arena

Karl V. Voelkerding, M.D., Medical Director, Advanced Technologies, ARUP Laboratories

The application of next-generation sequencing for clinical diagnostic purposes poses unique challenges due to technology complexity both at the wet bench and data analysis levels. The presentation will discuss approaches for streamlining technical processes and bioinformatic analyses to facilitate technology adoption into the clinic. Emphasis will be placed on the use of next-generation sequencing for targeted resequencing of multiple genes, which, when mutated, share overlapping clinical features.

12:15 pm Close of Morning Session

Sponsored by
Applied Biosystems NEW
12:30 Luncheon Presentation

The SOLiD™ 4 System – A Tool for Cancer Studies
Michael Rhodes, Ph.D., Senior Manager, Product Applications, Applied Biosystems


Sponsored by
Agilent Technologies

1:00 Luncheon Presentation
Targeted Capture and Resequencing of Cancer Exomes
Patrick Tarpey, Ph.D., Cancer Genome Project, Wellcome Trust Sanger Institute
We are interested in screening the coding exons and splice junctions of all genes in the human genome for somatically acquired mutations in human cancer. For this study we are using DNA from primary tumours and normal genomic DNA from the same individuals (matched pairs). To screen for small intragenic mutations, we have performed sequence capture using the Agilent SureSelect technology and a custom designed ‘Sanger exome’. This exome design contains all coding exons from the CCDS database plus additional protein coding exons taken from the HAVANA and ENSEMBL browsers. Captured DNA was sequenced using the Illumina GAII platform and variant detection performed using in-house algorithms.  To date, we have performed sequence capture on over 25 breast cancer, and 10 renal cancer matched pairs. The performance of this technology and the effectiveness of our analyses to detect somatic variants in primary tumours will be discussed.



2:00 Chairperson’s Remarks
Steve Lincoln, VP Scientific Applications, Complete Genomics, Inc.

2:05 Cancer Genome Sequencing - An Interim Analysis

Lawrence A. Loeb, Ph.D., Professor & Director, Gottstein Memorial Lab & Pathology, University of Washington

The multiplicity of mutations in human tumors supports the concept that cancers express a mutator phenotype. This has been reinforced by recent DNA sequencing studies which have documented hundreds to thousands of mutations in many human tumors. Most current technologies for DNA sequencing only identify the predominant substitutions at each nucleotide position, thus only detecting clonal mutations. Sequencing of single DNA molecules will be required to characterize the random mutations which act as a potential repository of drug resistance.

2:35 Comprehensive Resequence Analysis of a 97 kb Region of Chromosome 10q11.2 Containing the MSMB Gene Associated with Prostate Cancer

Meredith Yeager, Ph.D., Scientific Director, Core Genotyping Facility, NCI/NIH


3:05 NGS: The Bioinformatics Bottleneck
Richard Resnick, Vice President, Software and Professional Services, GenomeQuest, Inc.
Next-generation sequencing instruments are being placed by the hundreds while their throughput increases every quarter. Massive disk arrays, hundreds of thousands of cores of processing power, and tens of new mapping algorithms have been introduced to keep up. And yet the vast majority of researchers still wait months after their sequencing runs to get analyses to drive their science forward, while bioinformaticians scurry to keep pace. We will briefly present a free online NGS sequence data management (SDM) platform on the cloud produces interactive, mineable, shareable NGS analyses on not one but thousands of genomes, with an open API to allow bioinformaticians to develop and publish their own workflows for some or all to use.

3:20 Networking Refreshment Break, Poster Viewing & Final Exhibit Viewing

4:00 Analyzing Cancer “Omes” at Single Nucleotide Resolution

Nicole Cloonan, Ph.D., Senior Research Officer, Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland

With the scale of high-throughput sequencing technologies it is now possible to generate hundreds of millions of short sequences in a single experiment which has enabled the study of genomes, transcriptomes, and epigenomes at single nucleotide resolution. Using these techniques and technologies to systematically discover the mutations that have occurred in an individual cancer has enormous potential – not only for the discovery of novel tumor suppressors and oncogenes, but for personalized diagnostics and therapeutics. However, given the incredible scale of data being produced, there are bioinformatics hurdles to overcome before these techniques can be widely used in a clinical context. We will present on the kinds of bioinformatics analyses that are now possible, the biological insight that it is possible to derive, and the tools that are required to achieve this.

4:30 Identification of Deleterious Mutations in a Preterm Patient Genome

Justin Fay, Ph.D., Assistant Professor, Genetics, Washington University School of Medicine

Deleterious mutations make a significant contribution to human disease. We developed a likelihood ratio test to identify mutations that disrupt amino acids that are highly conserved across 32 vertebrate genomes. Application of this test to a preterm patient genome provides insight into the number and types of candidate mutations that may contribute to preterm birth.

5:00 Next-Generation Mendelian Genetics by Exome Sequencing

Sarah Ng, B.Sc., Senior Graduate Student, Genome Sciences, University of Washington

The comprehensive resequencing of all protein-coding regions (the “exome”) in a small number of unrelated, affected individuals is a cost-effective approach for gene discovery, particularly for rare monogenic diseases that have been thus far intractable by traditional gene mapping strategies. Using Freeman-Sheldon syndrome – a rare, dominantly inherited disorder as a proof-of-concept, we show that by sequencing the exomes of four unrelated affected individuals and then filtering out common variants, the causal gene can be identified.

5:30 Close of Day