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APPLICATION TRACK TECHNOLOGY TRACK Expression Analysis
Dr. Jeff Brockman, Psychiatric Genomics, Inc.
Dr. Achim Fischer, Axaron Bioscience AG
Dr. Philipp Kapranov, Affymetrix, Inc.
Dr. Barry Schweitzer, Protometrix, Inc.
Dr. Sun W. Tam, Texas Biotech CorporationCancer Arrays
Dr. David G. Beer, University of Michigan
Dr. Jeffrey Cossman, Gene Logic Inc.
Dr. Michael Gieseg, Pfizer Global Research and Development
Dr. Reena Philip, MetriGenix Inc.
Dr. Michael A. Tainsky, Wayne State University
Dr. Yihong Yao, Abbott Bioresearch CenterData Analysis
Dr. Raymond J. Cho, Ingenuity Systems, Inc.
Dr. Sorin Draghici, Wayne State University
Dr. Towia Aron Libermann, Beth Israel Deaconess Medical Center and Harvard Medical School
Dr. David Robbins, ViaLogy
Mr. William A. Schmitt, Jr., Massachusetts Institute of Technology
Dr. Joachim Theilhaber, Aventis PharmaceuticalsSurfaces/High-Density Arrays
Dr. Diping Che, Illumina, Inc.
Dr. Peter Herzer, Amersham Biosciences
Dr. Emile F. Nuwaysir, NimbleGen Systems, Inc.
Dr. Peter Thomsen, Scandinavian Micro Biodevices A/S
Mr. Andrew C. Tolonen, Massachusetts Institute of TechnologyProbes
Dr. Radoje Drmanac, Callida Genomics Inc.
Dr. Andy McShea, CombiMatrix Corporation
Dr. Niels B. Ramsing, Exiqon A/S
Dr. Timothy M. Straub, Pacific Northwest National Laboratory
Dr. Brian Ward, Sigma-Aldrich Corporation
Dr. Dong Xu, Oak Ridge National LaboratoryHybridization/Detection
Dr. Sergei G. Bavykin, Argonne National Laboratory
Dr. Robert Getts, Genisphere Inc.
Dr. David J. Graves, University of Pennsylvania
Dr. Saeed A. Khan, National Center for Toxicological Research, U.S. Food and Drug Administration
Dr. Michael Preston, Genicon Sciences Corporation
Dr. Arnold Vainrub, University of Houston
CLOSING PLENARY SESSION
Standards and Validation
Dr. Andrew I. Brooks, University of Rochester Medical Center
Dr. Robert L. Strausberg, National Cancer Institute
Dr. Stephen Tirrell, Millennium Pharmaceuticals, Inc.
Dr. Gregory J. Tsongalis, Hartford Hospital
The QUESTION: What can microarrays reliably provide and where are the greatest needs for improvement?
It depends upon whom you ask. While pharmaceutical and biotechnology researchers are divided on this question, both have a wide range of expectations for new technical developments. In terms of content, which one is best? Custom arrays, where content is defined by the user; theme arrays, where focus is centered around a disease or gene family; or whole-genome arrays, where content is defined by the species? All agree that sensitivity, high throughput, and automation are essential-but how do you best optimize format? With this "array" of possibilities comes the prerequisite of carefully assessing your specific purpose.The ANSWER: Macroresults can be achieved with microarrays if you know the question(s) to ask. Cambridge Healthtech Institute's Fourth Annual Macroresults for Microarrays will provide practical information and results about new technical developments to help you ask the right questions and determine which array is best for your specific application.
Conference Program
Monday, May 12
1:00-2:00pm Preconference Short Course Tutorial Registration
2:00-5:00 Preconference Tutorials
Short Course Tutorial One Designer Microarrays: From Soup to Nuts
Dr. Eugenia Wang, Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville
Designer microarrays are intended to provide microarray users with the methodology to focus their gene screening tasks on a defined group of genes, related by functionality or molecular regulation. This approach is needed for further screening among hundreds of candidate signature genes selected by large-scale gene screening, or for first-time users desiring to focus gene screening on a family of closely related genes. Designer microarrays may be obtained by two parallel tracks: (1) RNA sample preparation, probe labeling, and hybridization; and (2) producing the microarrays themselves. These two parallel tracks, followed by data mining, may be accomplished by separate teams, with the microarray production part out-sourced to commercial companies or by core facilities of academic institutes.
This course is intended for anyone interested in microarrays, from beginners to those seeking the next step after gene screening with large-scale microarray platforms.Short Course Tutorial Advanced Microarray Analysis
Dr. Atul Butte, Staff Informatician and Endocrinologist, Informatics Program, Children's Hospital, Harvard Medical School
Over three hours, I will interactively address moderate and advanced issues in microarray analysis, including multi-chip analysis, dealing with noise, measuring reproducibility, linking results to genes and other data, developing diagnostic patterns, web-based resources, and data visualization. Who should attend: functional genomics researchers and core facility personnel who are progressing past two chip or two group experiments.
5:00-6:00 Early Registration
Tuesday, May 13
7:30am Registration and Light Continental Breakfast
APPLICATION TRACK
TECHNOLOGY TRACK Expression Analysis
8:30 Chairperson's Remarks
Dr. Robert L. Strausberg, Director, Cancer Genomics Office, National Cancer Institute8:35 Whole-Genome Oligonucleotide Arrays: An Unbiased Way to Empirically Map the Transcriptome and Beyond
Dr. Philipp Kapranov, Staff Scientist, Affymetrix, Inc.
Recent completion of key genomic sequences, hallmarked by those of human and mouse, has provided unprecedented opportunities for the use of high-density oligonucleotide arrays to discover novel transcripts, to map functionally important genomic regions, and to integrate all this information in order to provide a global view of regulatory networks in the cell. For example, we have recently reported unexpectedly high levels of transcriptional activity in human chromosomes 21 and 22 using an annotation-independent approach based on oligonucleotide probes regularly spaced across genomic sequence. We have shown that up to an order of magnitude more genomic sequence can be transcribed into cytosolic mRNA than previously anticipated based on annotations of known exons in the human genome. This work has led to other ongoing studies involving the use of microarray technology to empirically detect and map hitherto unknown transcriptional units and functional elements in the human genome, which has profound implications for our current views of the genome's structure, regulation, and function.9:05 Gene Expression Profiling of Human Postmortem Brain Tissues: A Comparison of Affymetrix GeneChips®, Agilent cDNA Microarrays, and Q-PCR
Dr. Jeff Brockman, Senior Scientist and Microarray Group Leader, Psychiatric Genomics, Inc.
Gene expression profiling of human postmortem tissues presents unique challenges to microarray platforms. We have performed gene expression profiling on a set of 40 postmortem brain tissues using both Affymetrix U133A GeneChip® and Agilent Human 1 cDNA microarrays. Subsets of genes identified in this analysis were evaluated by quantitative real-time PCR. While there is a substantial overlap in the genes identified by both platforms, it is clear that each platform uniquely identifies a subset of differentially expressed genes. Currently, we are evaluating the effectiveness of both platforms for identifying differentially expressed genes in amplified samples of human brain tissue regions isolated by Laser Capture Microscopy. These results and multiple pitfalls that we have encountered in these studies will be discussed.9:35 Applications of Microarray Technology to Drug Discovery
Dr. Sun W. Tam, Manager, Charles River Laboratories
With the diverse advances in microarray technology, numerous applications of the technology can now be implemented in the drug discovery process. This presentation will focus on implementation of microarray technology in studies on drug target validation, drug mechanism of action, and preclinical development. Tissue arrays have been used to facilitate and accelerate the validation process. Protein arrays have been utilized to understand the physiology and pathology of animal models of disease in preclinical drug efficacy studies. DNA arrays have led to a "finger print" of drug action. Proper utilization of these platform technologies will significantly accelerate the pace of drug discovery and development.10:05 Poster and Exhibit Viewing, Refreshment Break
11:00 Interaction Analyses Using Whole Proteome Microarrays
Dr. Barry Schweitzer, Director, Technology, Protometrix, Inc.
The recent abundance of genomic data has created a need for a systematic proteomics approach to decipher the protein networks that dictate cellular function. To date, the generation of large-scale protein-protein interaction maps has principally relied on either yeast 2-hybrid or mass spectrometric techniques. In a landmark study by Snyder and coworkers at Yale University, the feasibility of using protein microarrays to investigate the function of a whole proteome was recently demonstrated. Protometrix has now developed the first product based on this technology, the Yeast ProtoArray™, which consists of the majority of yeast proteins printed on a glass slide. Data will be presented that demonstrate how protein-protein interaction information obtained from Yeast ProtoArrays™ complements and extends existing databases. Examples will also be given of how these arrays can be used for examining binding of a wide variety of molecules, including small molecules, peptides, and lipids.11:30 Whole Transcriptome Analysis by Signature Sampling Beyond the Array Limitations
Dr. Achim Fischer, Program Head, New Technologies, Axaron Bioscience AG
Axaron has developed a novel technology that can be described as a "virtual microarray." This technology overcomes today's limitations of microarrays and allows for complete unbiased expression profiling of any transcriptome of interest, including those of disease model organisms and agricultural species. This approach is using a matrix of 200x500=100,000 bins, of which each can be (but does not have to be) assigned to a gene expressed in a given biological sample, plus its respective expression level. After assignment and quantification for each "active" bin, a 20 bp sequence tag is determined that allows unambiguous identification of the expressed gene represented by this particular bin. Thus, a complete picture of the transcriptome is obtained, including relative expression levels of the active genes.12:00 Panel Discussion
12:30 Lunch (on your own)
Surfaces/High-Density Arrays
8:30 Chairperson's Remarks
Dr. Andrew I. Brooks, Assistant Professor and Director, Functional Genomics Center, University of Rochester Medical Center8:35 SpotOn™ DNA MicroArray Slide, a Novel Microarray Slide with a New Chemistry, Manufactured by SoftPlasma™ Technology
Dr. Peter Thomsen, Head of Research, Scandinavian Micro Biodevices A/S
SMB has developed a surface modification technology based on plasma: SoftPlasma™. This technology is characterized by superior control and stability. By SoftPlasma™ a carbonyl chloride surface for immobilization of amino-modified oligonucleotides has been deposited onto a high-quality microscope glass slide. Printing of amino-modified capture oligonucleotides onto the carbonyl chloride surface followed by hybridization with complementary labeled oligonucleotides resulted in excellent hybridization signals. The slide is resistant to boiling and to liquids in the range pH 3 to pH 11; it has low intrinsic background and a very active and uniform surface. It has been named SpotOn™ DNA MicroArray and has been shown to compare favorably to the 3D Link™ slide from Amersham Biosciences.9:05 Custom High-Density Oligonucleotide Arrays to Perform High-Throughput Expression Profiling
Dr. Emile F. Nuwaysir, Senior Manager, Technical and Client Services, NimbleGen Systems, Inc.
High-density oligonucleotide arrays have become a method of choice for large-scale gene expression studies. However, the relatively inflexible nature of the platform limits the usefulness of the tool. NimbleGen Systems has developed a method for the fabrication of high-density oligonucleotide arrays that eliminates the fundamental cost and time barriers associated with custom chip synthesis and requires only sequence information as input for array design and fabrication. These arrays allow entire genomes to be screened on a single array. For higher throughput applications, full genome coverage may not be necessary or desirable. These data are completely compatible with lower throughput, higher-information-content solutions provided by NimbleGen, allowing direct comparison of data between array formats.9:35 High-Performance Imaging System for High-Density Microarray Platform
Dr. Diping Che, Associate Director, Illumina, Inc.
Illumina has developed a BeadArray™ technology that supports SNP genotyping, mRNA expression analysis, and proteomics on the same platform. We use fiber optic bundles and microspheres to produce arrays with 3 mm features at a density of approximately 40,000 features/mm2. To facilitate high-throughput analysis of multiple samples, the fiber bundles are arranged in a matrix formation matching a 96- or 384-well microplate, so that many samples can be assayed in parallel. An automatic, high-resolution (~0.8 um), dual channel, confocal laser scanner is developed to support the BeadArray™ platform.10:05 Poster and Exhibit Viewing, Refreshment Break
11:00 Optimized in Situ Construction of Oligomers on an Array Surface
Mr. Andrew C. Tolonen, Graduate Student, Department of Biology, Massachusetts Institute of Technology
Recently, photolithography has been adapted as a powerful way to construct oligonucleotide arrays. Using this method, oligonucleotides are built base-by-base on the array surface by repeated cycles of photodeprotection and nucleotide addition. Broadly, we have investigated strategies to reduce the number of cycles required for oligonucleotide construction. By computer modeling oligonucleotide synthesis, we reduced the number of required synthesis cycles by focusing upon how oligonucleotides are chosen from within genes and upon the order in which nucleotides are deposited. In this talk, I will discuss how these strategies can be used to streamline the construction of oligonucleotide arrays.11:30 Gene Expression Profiling of Multiple Biologic Systems Using Amersham Biosciences' CodeLink™ Bioarray System
Dr. Peter Herzer, Gene Expression Applications Consultant, Amersham Biosciences
The use of microarray technology to monitor gene expression in pathophysiologic model systems has lead to better understanding of the mechanisms underlying these events. CodeLink™ from Amersham Biosciences is a bioarray systems solution for accurate high performance, highly reproducible gene expression profiling. We have utilized CodeLink Expression bioarrays to investigate the effect of the hepatotoxic agent, carbon tetrachloride, on rat liver gene expression patterns; analyzed the effect of corticosteroid treatment in a human inflammation model; and in collaboration with the Mount Sinai School of Medicine, we have examined a hepatocellular carcinoma study. In all cases we have identified predictive and reproducible patterns across a small set of genes that reflect effects of the biologic system. This will ultimately lead to improved predictive accuracy of mammalian models to the humansystem in the context of pharmacogenomics.12:00 Panel Discussion
12:30 Lunch (on your own)
1:30 Technology Workshops
(Build your own sundae and experience what new microarray technologies have to offer.)
New Microarray Technologies, Pins and Plates
Presented by Dr. Ezra Abrahams
Dr. Brian Patterson, and Mr. Colin Reynolds>
Sponsored by: Managing Microarray Data:
Who Thought It Could Be This Easy?
Presented by Mr. Jason Goncalves, Iobion Informatics>
Sponsored by: Mergan's Prokarayotic Arrays
Presented by Jaime Love, PhD, MBA, Director of Business Development, Mergen Ltd.>
Sponsored by: Cancer Arrays
2:30 Chairperson's Remarks
Dr. Michael A. Tainsky, Professor and Director, Program in Molecular Biology and Genetics, Barbara Ann Karmanos Cancer Institute, Wayne State University2:35 Using Transcrip Profiling to Compare KDR Inhibitor Chemotypes in a Disease Model and in HUVEC Cells
Dr. Yihong Yao, Senior Scientist, Abbott Bioresearch Center
Vascular endothelial growth factor (VEGF) has been shown to be the primary mediator of angiogenesis. Two high affinity VEGF receptor tyrosine kinases, KDR/flk-1/VEGFR-2 and flt-1/VEGFR-1, have been identified almost exclusively on endothelial cells. VEGF has also been identified as a potent inducer of vascular permeability and recent evidence has implicated this molecule in the development of pathological edema. We have applied Affymetrix Genechips to cell based and animal model systems to better understand the role of KDR in VEGF signaling and to profile KDR inhibitors. We find in both models many regulated genes that are co-cited with VEGF and/or angiogenesis and known to be involved in VEGF/KDR signal transduction. Because the various compound classes profiled in this study have overlapping effects on VEGF dependent gene expression, we are able to distinguish on and off target effects. These results not only provide insights into signaling ev! ents necessary for angiogenesis but also a basis for prioritizing lead candidates.3:05 Molecular Diagnosis of Non-small Cell Lung Carcinomas by Gene Expression Profiling
Dr. Reena Philip, Scientist, MetriGenix, Inc.
We analyzed high-density DNA microarray data sets from normal and diseased lung tissues with the goal of identifying biological markers for classifying non-small cell lung carcinomas (NSCLC). After performing gene signature differential analysis, fold change, linear discriminant analysis, and principal component analysis (PCA), 20 genes were identified as sufficient to separate NSCLC and normal lung samples. The in silico findings were validated with quantitative RT-PCR (TaqMan) and the MetriGenix 4D Array (MGX 4D array) system. As tested with total RNA from normal and tumor lung tissues, the MGX 4D chip results yielded consistent results with expression data from high-density DNA microarrays and quantitative RT-PCR. Combination of data mining and MGX 4D array system will provide an accelerated platform for target identification and validation and potentially for diagnostics.3:35 Integrating Multiple Analyses Platforms for the Analysis of the Same Tumor Samples
Dr. David G. Beer, Professor, Department of Surgery, and Director, General Thoracic Surgery Tumor Biology, University of Michigan
The identification and treatment of those patients with stage I lung adenocarcinoma who may be at increased risk for progression may help increase patient survival. Quantitative 2D-PAGE and oligonucleotide arrays were applied to the analysis of the same series of 86 lung tumors and 10 normal lung samples. Preparation of DNA and construction of tumor tissue microarrays from the same samples were used to facilitate the further characterization of candidate genes/proteins predictive of patient survival. A risk index based on the top genes or proteins most correlated with patient survival was able to predict outcome among patients with early-stage lung adenocarcinomas.4:05 Poster and Exhibit Viewing, Refreshment Break
4:45 High-Throughput Analysis of Tumor Antigens for Cancer Diagnostics Using Protein Microarrays
Dr. Michael A. Tainsky
Cancer is highly curable if diagnosed early, but those who are diagnosed with it at a late stage have a very poor prognosis. We have developed a novel screening tech-nology for early detection of ovarian cancer using T7 phage display cDNA libraries. We use selective biopanning to isolate clones of antigens reacting with antibodies present specifically in the sera of patients with ovarian cancer. The goal is to use serum antibody reactivity to proteins expressed in ovarian tumors as diagnostic bio-markers. The antibody reaction to large numbers of these antigens is detected in a highly parallel assay on robotically spotted microarrays of the proteins. By assaying serum antibodies from patients and controls with two-color fluorescence detection on antigen microarrays, we can differentiate women with ovarian cancer from healthy women without false positives due to other gynecological syndromes classically con-founding other diagnostic technologies.5:15 Molecular Characterization of Tumor Models by RNA Expression Profiling
Dr. Michael Gieseg, Senior Scientist, Cancer Pharmacology, Pfizer Global Research and Development
Preclinical animal models of human tumors represent a major tool for the selection of effective anticancer agents. New genomic technology allows molecular characterization of these models to an extent never possible before and provides data that aid biological understanding of their molecular properties and quality control. We have generated RNA expression profiles for a collection of human tumor xenografts and examined relatedness and expression variation among replicate samples.5:45 Utility of an Oligonucleotide Microarray Expression Reference Database in Gene Discovery in Cancer
Dr. Jeffrey Cossman, Vice President and Medical Director, Gene Logic Inc.
Gene expression profiling was performed on an oligonucleotide microarray platform for simultaneous analysis of 45,000 probe sets representing more than 39,000 transcripts derived from approximately 33,000 well-substantiated human genes. Gene expression data in the Gene Logic's BioExpress™ Module were analyzed using existing GeneExpress® Software System tools (fold change analysis, contrast analysis and e-Northern™), ANOVA, and Principal Component Analysis (PCA). The expression profiles of cancer-specific genes are readily available in over 7000 human pathologically normal, diseased, benign and tumor samples from over 60 tissue types. The profiles are important in the determination of usability of the cancer-specific genes as drug targets or diagnostic markers.6:15 Networking Reception in the Exhibit Hall
7:30 Close of Day One
Probes
2:30 Chairperson's Remarks
Dr. Timothy M. Straub, Senior Research Scientist, Environmental Microbiology Group, Pacific Northwest National Laboratory2:35 Callida Genomics: Advancing Genomics through Universal Probe Technologies
Dr. Radoje Drmanac, Chief Scientific Officer, Callida Genomics Inc.
Callida Genomics is developing advanced DNA sequence analysis products utilizing proprietary universal probe and sequencing by hybridization (SBH) technologies. Universal probe sets are designed based on statistical principles and can be used to analyze any mutation in any gene from any species. Universal probe products have broad applications in drug development, medical diagnostics, crop/livestock improvements, and biosciences research. We are currently designing a series of universal probe products on several common assay platforms including single molecule analysis technologies with the potential to perform routine whole genome sequencing. The HyChip™ system scores a complete set of four million 11-mer probes for the accurate sequencing of any gene. These universal probe technologies and associated products will help revolutionize the fields of personal and preventive medicine.3:05 The Universal LNA Array: "One Chip Fits All"
Dr. Niels B. Ramsing, Director for New Technlogies, Exiqon A/S
Several basic limitations restrict widespread use of DNA array technology in research as well as in vitro molecular diagnostics. Many genes and pathways are still unknown, and our understanding of nucleic acid hybridization is still limited. An elegant solution would be to put all possible capture sequences on one chip and use the same universal chip for all capture experiments (= "One-Chip-Fits-All"). A universal LNA array consisting of all possible oligonucleotides of a given length can be used as a general purpose tool to obtain temperature-dependent hybridization patterns
(= DNA signatures). These detailed signatures may be classified/analyzed by comparison to a large set of standard signatures. Furthermore, it is possible to compare a sample signature to the best possible combination of standards to determine the goodness of fit, i.e., if a linear combination of the known standards adequately describes the sample. This feature is essential for medical applications, where it will be possible to identify samples that cannot be resolved reliably with this technique.3:35 Chemistry of Printed Nucleic Acid Microarrays
Dr. Brian Ward, Principal Investigator Sigma-Aldrich Corporation
Printing nucleic acids on glass microscope slides is a routine part of a microarray experiment. Because unmodified nucleic acids are not irreversibly immobilized on plain glass, microscope slides need to be coated to allow sufficient probe to be present on the slide surface for target capture and detection. Glass is thus coated by adsorptive (e.g., with poly-l-lysine) or covalent (e.g., with silanes) means to enable probe immobilization. Most commonly used amine modified surfaces (i.e., poly-l-lysine and aminopropyl silane) immobilize nucleic acids by a combination of coulombic attraction and surmised covalent bonding. Because binding of nucleic acids to these surfaces likely encumbers hybridization of some parts of the printed sequence, many strategies generally using amine or thiol chemistry borrowed from the bioconjugationists toolbox have been developed that attempt to tether nucleic acids to surfaces in predictive ways. The hope of these studies is to develop a tethering method that allows unencumbered probe-target hybridization. To enable an understanding of immobilization chemistry, glass as a substrate, silane chemistry, nucleic acid tethering, and covalent mechanisms will be reviewed.4:05 Poster and Exhibit Viewing, Refreshment Break
4:45 PRIMEGENS: Robust and Efficient Design of Gene-Specific Probes for Microarrays
Dr. Dong Xu, Staff Scientist, Protein Informatics Group, Life Sciences Division, Oak Ridge National Laboratory
We developed a bioinformatic tool, PRIMEGENS, for the automatic design of PCR primers using DNA fragments that are specific to individual open reading frames (ORFs). PRIMEGENS first carries out a BLAST search for each target ORF against all other ORFs of the genome to quickly identify possible homologous sequences. Then it performs optimal sequence alignment between the target ORF and each of its homologous ORFs using dynamic programming. PRIMEGENS uses the sequence alignments to select gene-specific fragments and then feeds the fragments to the Primer3 program to design primer pairs for PCR amplification. The program runs efficiently and reliably, as tested using Shewanella oneidensis MR-1 and Deinococcus radiodurans R1.5:15 A Novel Semiconductor-Based Microarray Platform for Rapid Development and Validation of Gene Expression Diagnostic Assays
Dr. Andy McShea, Director, Applied Science, CombiMatrix Corporation
The CombiMatrix technology platform is a combination of semiconductor technology and chemistry designed for applications in pharmaceutical development and the life sciences. Precise, digital control of a highly efficient electrochemical detritylation process allows this oligo array system to be used for a wide range of applications beyond the scope of conventional DNA arrays. This system is easily miniaturized at low cost. Embedded sensing circuitry is designed into the semiconductor substrate, which can provide a more sensitive alternative to conventional fluorescence technology. The chip layout and sequences are fully customizable, and the rapid cycle times allow highly iterative experimental approaches through intuitive software interfaces. Elements of this technology have been incorporated into the "matriXarray" product line, available through our partnership with Roche Applied Sciences.5:45 Development of New Microbial Source Tracking Methods Using Random Nonamer Oligonucleotide Microarrays
Dr. Timothy M. Straub
Current DNA fingerprinting techniques to identify sources of microbial pathogens lack adequate resolving power for differentiating closely related isolates. A majority of these techniques rely on band sizing techniques that can be extremely difficult to interpret if differences between isolates vary in length by just a few bases. To address this, we are developing a random DNA fingerprinting microarray, automated image analysis tool, and requisite statistical algorithms for identifying and comparing microarray fingerprints, for the purpose of tracking pathogenic microorganisms in environmental systems and nonhuman vectors. Data will be presented showing the approach's potential use for fingerprinting Xanthomonas pathovars and Salmonella enterica isolates. Preliminary data also suggests that this technique may be applicable for tracking movements and survival of hatchery-raised salmon.6:15 Networking Reception in the Exhibit Hall
7:30 Close of Day One
WEDNESDAY, MAY 14
7:30am - 8:15am Breakfast Workshop Sponsored by
Alternative Splicing, Endogenous Antisense Genes, and Transcription Annotation: Implications for Probe Design and Gene Expression Analysis
Presented by Brian Meloon, Ph.D., Compugen, Inc.
8:00am Poster and Exhibit Viewing and Light Continental Breakfast
Data Analysis
8:30 Chairperson's Remarks
Dr. Sorin Draghici, Assistant Professor, Department of Computer Science, Wayne State University8:35 Pathways-Centric Analysis of Gene Expression during Neural Development
Dr. Joachim Theilhaber, Research Scientist, Cambridge Genomics Center, Aventis Pharmaceuticals
Using Affymetrix chips, we have obtained expression profiles for ~60,000 gene transcripts, across a time series of six neuronal developmental stages (with multiple biological replicates) and for matched tissue samples from two regions of the developing fetal brain, the cerebral cortex, and the ventricular zone. The ventricular zone is a germinative region in which initially proliferating stem cells undergo successive differentiations into neurons or glial cells before finally migrating outward into the cerebral cortex. This expression data set has been analyzed by focusing on a number of key pathways, central to neural and glial cell development, with an emphasis in each case on ultimate transcriptional targets. We will present statistical methods for scoring and comparing pathways, for integrating information from known or inferred common cis-regulatory motifs, and, finally, for the supervised classification of unassigned genes in accordance to their observed role in the known pathways.9:05 DNA Quantitation in a Complex Nonlinear Environment
Dr. David Robbins, Director, Microarray Applications, ViaLogy
Comparison of signal intensities from two or more sample sources is commonly performed in order to estimate the probability that a given gene or protein is up- or downregulated relative to another. What manufacturing and experimental variances prevent the direct use of signal intensity for quantitation? A better question might be: Given these process variances, how can observed signal intensities be converted into quantitative results? We will describe our computational approach, stemming from the application of Quantum Resonance Interferometry (QRI) to signal detection analysis, and outline the experimental requirements to adapt the algorithms to a specific instrumentation platform.9:35 Onto-Tools: From Data Analysis to Biology and Back
Dr. Sorin Draghici
Most of the current efforts in microarray data analysis are focused on providing tools and methods for sifting through the large amount of raw data generated by microarrays in order to obtain a set of genes that are differentially regulated in the condition(s) under study. A plethora of tools exists for image processing, pre-processing, clustering, and calculating statistical confidence. Usually, once such differentially regulated genes are found, the data analysis process is considered done and the biologist reverts once again to a tedious process of individually analyzing each differentially expressed gene in an attempt to understand the biological phenomenon involved. This talk will present Onto-Express, a tool for the post-gene-selection analysis as well as a number of other related tools. The talk will present the tools as well as examples showing their utility. The Onto-Tools are freely available at http://vortex.cs.wayne.edu/Projects.html.10:05 Poster and Exhibit Viewing, Refreshment Break
10:45 DNA Microarray Data Sample Size Required for Discriminatory Expression Patterns
Mr. William A. Schmitt, Jr., Department of Chemical Engineering, Bioinformatics and Metabolic Engineering Laboratory, Massachusetts Institute of Technology
We have applied power analysis to estimate the minimum sample size required for two-class and multi-class discrimination from DNA microarray experiments. The power analysis algorithm calculates the appropriate sample size for discrimination of phenotypic subtypes in a reduced dimensional space obtained by Fisher Discriminant Analysis (FDA). This approach was tested by applying the algorithm to existing data sets for estimation of the minimum sample size required for drawing certain conclusions on multi-class distinction with statistical reliability. It was confirmed that when the minimum number of samples estimated from power analysis is used, group means in the FDA discrimination space are statistically different.11:15 A Knowledge-Based Approach to Functional Network Analysis of Gene Expression Data
Dr. Raymond J. Cho, Vice President, Genomics, Ingenuity Systems, Inc.
We have used a frame-based approach to formally structure more than 600,000 individual scientific findings for the purposes of sophisticated, pathways level analysis of human and mouse biological systems. Network analysis on gene expression data reveals regulation both novel and studied pathways, suggesting a systematic means for general genomic analysis. The underlying technological platform has been designed to enable capture of proprietary knowledge to flexibly support a range of therapeutic discovery applications, providing a unique target validation solution for biopharmaceutical research.11:45 Functional Genomics and Proteomic Approaches to Human Cancer
Dr. Towia Aron Libermann, Associate Professor of Medicine, Director, BIDMC Genomics Center, Beth Israel Deaconess Medical Center and Harvard Medical School
Genomic and proteomic technologies have the promise to rapidly generate multiple disease hypotheses due to the parallel query of hundreds of thousands of data points and to drastically cut the time and costs involved in target validation. We will outline our systematic and comprehensive functional genomics strategies for transcriptional profiling, high-throughput genotyping, proteomics, and drug screening to define disease mechanisms at a molecular level and to identify novel prognostic and predictive markers as well as new drug targets in human cancer. We will present specific examples on prostate, ovarian, and renal cancer for our functional genomics approach. We are applying novel bioinformatics tools to integrate all the data across divergent platforms in order to generate new disease hypotheses by computational means. We will present several practical examples in cancer for streamlining and accelerating the process of disease hypothesis generation and target validation.12:15 Luncheon in the Exhibit Hall
Hybridization/Detection
8:30 Chairperson's Remarks
Dr. Arnold Vainrub, Research Assistant Professor, Department of Chemistry, University of Houston8:35 Radical-Generating Coordination Complexes as New Tools for Rapid Labeled Sample Preparation in DNA Microchip Technology
Dr. Sergei G. Bavykin, Molecular Biologist, BioChip Technology Center, Argonne National Laboratory
A new method based on using radical-generating complexes for the simultaneous labeling and random fragmentation of both single- and double-stranded forms of RNA and DNA has been developed. Nucleic acids labeled with the OP-Cu and the Fe-EDTA protocols revealed high hybridization specificity in hybridization with DNA microchips containing oligonucleotide probes. Labeling and fragmentation of cDNA and cRNA were also used with this method. Following the OP-Cu protocol, it takes only 1 minute at 95°C to complete the labeling-fragmentation reaction.9:05 Resonance Light Scattering (RLS) Particles for Ultrasensitive Detection of Nucleic Acid and Protein Analytes on Microarrays
Dr. Michael Preston, Technical Consultant, Genicon Sciences Corporation
RLS Particles™ are ultrasensitive labels that have been implemented across a wide variety of analytical bioassays. The RLS signal generation and detection system has been used to detect protein and nucleic acid analytes with ultrasensitivity on microarrays. The linear dynamic range of analyte detection with RLS Particles is greater than three orders of magnitude. Properties of RLS Particles and their application to nucleic acid and protein arrays will be described.9:35 Oligonucleotide Microarray as an Electrostatic Device
Dr. Arnold Vainrub
We present a novel model of oligonucleotide microarray as an interface electrostatic device extending the traditional hybridization sensor concept. The approach is validated by comparison with recent experiments demonstrating drastic interface electrostatic effects. We discuss the key mechanism, the Coulomb blockage of on-array hybridization due to the electrostatic repulsion of the assayed nucleic acid from the layer of surface immobilized DNA probes, and derive the on-array hybridization isotherm. To demonstrate the potential practical impact, we present examples of modeling and optimization of surface parameters (probe density and length, surface charge, linker type) and solution conditions (hybridization temperature, ionic strength, target length, and concentration) for two major microarray applications, sensitive gene expression assay and multiplexed SNP detection.10:05 Poster and Exhibit Viewing, Refreshment Break
10:45 Development of a Random Prime Labeling Method Using Fluorescent 3DNA™ Dendrimers and Use with Small Degraded RNA Samples
Dr. Robert Getts, Senior Scientist, Genisphere Inc.
As microarray technology advances, the trend in the field is to work with more limiting amounts of RNA and with RNA samples that are purified from tissues or cells that may have been collected under unfavorable conditions. We have developed a new adaptation of the 3DNA™ microarray labeling technology based on random prime synthesis of cDNA. This method works well with RNA samples sizes in the 0.5- to 2-microgram range, and we observed that partially degraded RNA samples perform nearly as well as their undegraded counterparts in microarray experiments. A correlation of 0.98 was observed when comparing an RNA sample to its degraded counterpart. Experiments summarizing the development of the 3DNA™ random prime labeling method as well as describing the expression studies using intact and degraded samples will be presented.11:15 Microarray Detection of Multiple Antibiotic Resistance Markers in Competitive Exclusion Product Preempt™ and Food-Borne Pathogens
Dr. Saeed A. Khan, Research Microbiologist, Division of Microbiology, National Center for Toxicological Research, U.S. Food and Drug Administration
An oligoarray method to detect the presence of 131 antibiotic resistance markers corresponding to 22 different antibiotics was developed. The sensitivity and specificity of hybridization data were established by antisense oligo hybridization. This was further tested by hybridization of Cy3-labeled cDNA obtained after RT and RT-PCR reactions using total RNA from the food-borne pathogens and from the preempt™ product. Labeled cDNA generated after RT-PCR reaction gave more reproducible hybridization results than cDNA generated after RT reaction alone. The method has a potential use in screening the presence of multiple antibiotic resistance markers in future competitive exclusion products, food-borne pathogens, and other clinical isolates.11:45 Ten-Minute Microarray Hybridizations
Dr. David J. Graves, Professor, Department of Chemical and Biomolecular Engineering, The University of Pennsylvania
Use of a new type of coated slide and a simple change in operating procedure can result in hybridizations that occur 20 to 50 times faster than normal. This is the result of an electric field that concentrates nucleic acid molecules at the surface. A small spacing between electrodes and a very low potential prevent destructive electrolysis products from forming and affecting results. Standard spotting equipment can be used to prepare microarrays on the treated surfaces at any desired spot density.12:15 Luncheon in the Exhibit Hall
Standardization and Validation
1:30 Chairperson's Remarks
Dr. Robert L. Strausberg1:35 Assessing the Source4s of Variability in Microarray Data: A Multi-institutional Study Microarray Variability and Standards
Dr. Andrew I. Brooks, Assistant Professor and Director, Functional Genomics Center, University of Rochester Medical Center
The employment of high-throughput gene expression technologies such as DNA microarrays has presented many challenges in the areas of experimental design and data analysis. Studies that employ DNA microarray technology must address, at some level, technological variability in order to be effectively used as a tool for biological discovery. To this end, the identification of potential sources of variability in microarray data allows the experimentalist to address important factors that can be accounted for in both experimental design and data treatment. The topics to be discussed include the identification of factors not associated with biological activity that may contribute to variation in microarray results. A series of protocols and procedures will be presented that can help standardize DNA microarray data allowing for cross platform analysis as well as foster effective data sharing across multiple institutions.2:05 Microarray Process Control Initiative
Dr. Stephen Tirrell, Director, Transcriptional Profiling, Millennium Pharmaceuticals, Inc.
As pharmaceutical and biotechnology scientists expand the application of microarray technology from target discovery to downstream clinical applications the need for integrated process controls becomes increasingly important. To meet these demands we have developed standardized methods for monitoring key quality metrics of the Affymetrix Genechip system. Integrating these operational policies and procedures with a centralized high-throughput core facility has proven to be a complex but effective means for monitoring data quality. Quality control methods and data for target discovery and clinical samples will be reviewed.2:35 Quality Assurance and the Microarray: The Leap into a Clinical Laboratory
Dr. Gregory J. Tsongalis, Director, Molecular Pathology, Hartford Hospital
Advances in microarray technologies have made it possible to screen thousands of genomic targets in pursuit of a better understanding of the pathogenesis of disease. The data presented in numerous published manuscripts have established this technology as a revolutionary tool that may be applicable in a clinical setting. This presentation will review general quality assurance practices and specific issues related to microarrays.3:05 Poster and Exhibit Viewing, Refreshment Break
3:45 Interactive Roundtable Discussion on Standards and Validation
Microarray technology offers an unprecedented opportunity to peer into activities of normal and diseased cells and tissues. In addition, enormous value can be achieved through developing databases, which include the plethora of data being produced by the greater community; thus results from individual experiments can be viewed and compared using a much wider scientific window. Standardization and validation are key to developing effective databases and are critical when planning an effective interface to expand applications of microarray technology from basic to clinical research. Each roundtable panel member will discuss his use of microarray technology and goals in developing standards and validation procedures for specific applications. The roundtable will conclude with a question-and-answer session with the audience.Panel Moderator: Dr. Robert L. Strausberg
Panel Participants: Dr. Andrew Brooks; Dr. Diping Che; Dr. Richard Shippy, Amersham Biosciences; Dr. Dile Holton, Product Manager, PerkinElmer Life and Analytical Sciences; Dr. Thomas Ryder, Senior Director of Assay Development, Affymetrix; Dr. Stephen Tirrell; Dr. Gregory J. Tsongalis
Corporate Sponsor Biographies:
Apogent Discoveries, consisting of BioRobotics, Matrix Technologies, and Robbins Scientific, supplies high-quality consumables and instrumentation to the pharmaceutical and biotech industries. Apogent Discoveries' product portfolio comprises a wide range of automated liquid handling systems, microarray fabrication robots, and other specialty equipment and disposables for high throughput, molecular biology, and genomic applications.
Iobion Informatics presents GeneTraffic software for two-color microarray data management and analysis. GeneTraffic software allows you to access data and projects on a desktop PC, from any location within your network, manage data, perform computational analyses, and query your data. With GeneTraffic software you can qualify and validate your microarray data prior to biological analysis.
Iobion Informatics is a Delaware LLC, headquartered in La Jolla, California with offices in Toronto, Canada, and Austin, Texas.
Gene Logic, Inc. is a leading provider of innovative functional genomics information products, services and bioinformatics tools, which focus on human biology and pathology. Our primary objective is to become an indispensable partner for drug discovery and development research by providing biological information and in silico analysis products and related services that impact pharmaceutical and biotechnology pipeline bottlenecks.
Mergen is a San Francisco bay area biotech company focused on oligo-based DNA microarray technology. Our mission is to provide the highest quality microarrays and services to the pharmaceutical, biotech, and research customers. Mergen's ExpressChip™ DNA Microarray system includes human, mouse, rat, and Staph aureus arrays.
Sponsoring Publications:
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CHI's Life Sciences Informatics
Web Partners:
In addition to exhibiting, many sponsorship opportunities are available for your company to maximize its exposure and influence. They include overall event and conference specific sponsorships, technology workshops, networking receptions, delegate bags, and badge lanyards. For more information on available sponsorship packages and exhibit space, please contact Angela Parsons at 781-972-5467 or aparsons@healthtech.com.
CALL FOR POSTERS
Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the poster sessions. Please fill out the registration form, with the poster title and primary author. To ensure inclusion in the conference CD, a one-page summary must be submitted and registration must be paid in full by April 4, 2003. Click here for poster instructionsCONFERENCE VENUE
World Trade Center
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T: 617-385-5049HOTEL INFORMATION
Seaport Hotel
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Room Rate: $189 S/D
Cut-off Date: April 21, 2003Please call the hotel directly to make your room reservation. Identify yourself as a Cambridge Healthtech Institute conference attendee to receive the reduced room rate. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space-and-rate-availability basis. Rooms are limited, so please book early.
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