(Formerly Microarray Data Analysis)
THURSDAY, SEPTEMBER 25
7:30 am Breakfast Technology Workshop
8:15 Successful Statistical Strategies Discussion Groups
Time has been designated for facilitated discussion groups with specific themes. This unique opportunity allows conference participants to focus on a topic and exchange ideas, information, experiences, and develop future collaborations.
COPY NUMBER ANALYSIS:
APPLYING THE RELIABILITY OF DNA TO CLINICAL DIAGNOSIS
9:00 Chairperson’s Remarks
Thomas J. Downey, President, Partek, Inc.
9:05 Copy Number Variation in Genetic Disorders: New Insights for Diagnostics and Candidate Gene Discovery
Christian Marshall, Ph.D., Centre for Applied Genomics, Program in Genetics & Genome Biology, Hospital for Sick Children
Copy number variation (CNV) has recently been shown to represent a significant amount of genetic variation in healthy individuals, but also contribute to complex genetic disorders. Although the overall incidence of CNV in genetic disorders is not known, advances in technology resolution can aid in clinical diagnostics and candidate gene discovery. This talk will focus on CNV data generated from genome-wide scans of patients with complex genetic disorders, including autism spectrum disorders, and discuss strategies for determining if a particular variant may be pathogenic or benign.
9:35 Human Genome Structural Variation Project
Gregory Cooper, Ph.D., Postdoctoral Fellow, Eichler Lab, Department of Genome Sciences, University of Washington
Copy-number variants (CNVs) are become increasingly appreciated as major contributors to human genomic diversity and as influences on human traits. We analyzed Illumina genome-wide SNP array data for several large collections of ‘normal’ adult individuals, totaling more than 2,500 samples. Interestingly, we observe that large (> 200 kbp) deletion and duplication events occur in at least 10% of adults, with events as large as 1 Mbp in many individuals. Some of these events occur in loci previously hypothesized to contribute to severe early childhood diseases. Our results suggest that pathogenicity of even very large CNVs can be uncertain without large numbers of control samples, and further confirm that genomic structural variation is common in human populations.
10:05 Analysis of Copy-Number Variants in Association Studies for Complex Traits
Iuliana Ionita-Laza, Ph.D., Department of Biostatistics, Harvard School of Public Health
Though there is increasing support for an important contribution of copy number variation (CNV) to the genetic architecture of complex disease, few methods have been developed for the analysis of such variation in the context of genetic association studies. In this talk, I will discuss a generalization of family-based association tests (FBAT) to allow for the analysis of CNVs at a genome-wide level. I will illustrate the approach with an application to a CNV genome-wide-association study of asthma.
10:35 Morning Coffee
10:55 Institution-Wide Copy Number Analysis: Bridging the Gap Between Research and Diagnostics
Anton Petrov, Ph.D., Scientific Director, infoQuant Ltd.
Array CGH are becoming widely accepted for diagnostics of various diseases and for development of personalized medicine. We would like to highlight major challenges in analyzing aCGH-based copy number profiles. Various types of issues have to be considered for successful implementation of modern copy number analysis. Such issues range from scalability of employed algorithms to integration of publicly available CNV information and accumulation of internal CNV data. We would like to demonstrate how these issues can be addressed in a framework of institution-wide copy number analysis system.
11:25 Panel Discussion with Morning Speakers
11:55 Close of Session
12:15 pm Luncheon Technology Workshop (Sponsorship Available)
SEQUENCING – ENABLING PERSONALIZED MEDICINE?
2:00 Chairperson’s Remarks
Kevin Davies, Ph.D., Editor-in-Chief, BioIT World
2:05 KEYNOTE PRESENTATION
An Integrated Data Warehouse for Biomedical and Translational Research
John Quackenbush, Ph.D., Professor, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute
The critical components of modern biomedical research are patient samples and their associated clinical data. However, in most research environments, the data is scattered across many fragmented and often incompatible databases. Similarly, there exists a vast body of public data, including sequence and gene expression repositories, the biomedical literature, and countless other sources of information that, though available, are often not readily accessible for large-scale automated analysis. To address these issues and accelerate research, we have developed a data warehouse and a series of data portals that, driven by common research use cases, provide an integrated picture of biomedical research data.
2:40 Absolute Transcript Counting by Single Molecule Sequencing
Tal Raz, Ph.D., Group Leader/Senior Scientist, Methods Development, Helicos Biosciences
We have developed a transcript counting method using single molecule sequencing to generate unbiased and accurate quantification for the complete transcriptional dynamic range of typical cells. Our method is not subject to the typical biases inherent to most digital gene expression (DGE) profiling. In addition, we apply a computational method for eliminating counting inaccuracies that may be caused by read misassignment. We demonstrate the application of single molecule transcript counting that requires no ratiometric measure between samples for accurate inventorying of the complete transcriptome of a Saccharomyces cerevisiae mRNA and a human placenta mRNA. We compare our results to microarray and qPCR measurements and demonstrate the ability to quantify low-abundance transcripts.
3:00 Targeted Extraction of Specific Non-Contiguous Loci on Mouse Chromosome 1 for Next-Generation Sequencing with HybSelectTM
Daniel Summerer, Ph.D., febit, gmbh, Heidelberg, Germany
The introduction of next-generation sequencers has lead to a dramatic increase in sequencing throughput. Besides whole genome de novo sequencing of small genomes, high throughput re-sequencing of selected regions of a large, eukaryotic genome is now available. However, these selected regions have to be separated from the remaining chromosomal DNA first due to the high complexity of the sample. We will report an approach termed HybSelect™ which makes use of target-specific DNA extraction using Geniom® Biochips. We demonstrate the targeted enrichment of a set of 100 non-contiguous loci on the mouse chromosome 1. We were able to recover picograms of highly enriched DNA that was further analyzed by qPCR and on an Illumina/Solexa Genome Analyzer.
3:20 Shotgun Sequencing by Hybridization: Simple, High-throughput and Low Cost
Benoit Houle, Ph.D., Senior Director, Technology Development, Genizon BioSciences
3:50 Close of Session
4:00 Close of Meeting