Thursday, April 12
8:30
Chairperson’s Opening Remarks
Robert S. Negm, Ph.D.,
Vice President, GenTel BioSciences
| Keynote
Presentations:
8:40
Step 1: Harvest Tissue; Step 2: Prepare Template
Michael Brownstein,
M.D., Director of Functional Genomics, Craig Venter Institute
Investigators who are new to the field of functional genomics
are put off by the apparent difficulties inherent in labeling probes,
hybridizing and washing arrays, and analyzing results.
This is perfectly appropriate, but assuming that preparing nucleic
acids for one’s studies is trivial, would be incorrect.
Attention to detail and quality control are essential and different
applications demand different templates.
I will give examples of the latter and describe novel amplification
methods that allow experiments to be done today that were impossible to
imagine a few years ago.
9:20
Robust Data, Robust Algorithms: From Preanalytical Variability to
Bioinformatic Analysis
Dr. Stephen R. Master,
Assistant Professor, Department of Pathology and Laboratory Medicine,
University of Pennsylvania Health System
Several recent studies have demonstrated the importance of
controlling preanalytical variability during sample collection for genomic and
proteomic assays. Further, both
preanalytic and analytic variation can have a profound impact on the ultimate
outcome of highly multiplexed diagnostic tests.
We will discuss sources of this variation as well as the importance of
choosing appropriate bioinformatic analyses in in order to maintain test
quality.
|
10:00 Grand
Opening Refreshment Break in Exhibit Hall
11:00 Chairperson’s
Remarks
Robert S. Negm, Ph.D., Vice
President, GenTel BioSciences
11:05 Global
Changes in microRNA Expression during Human Embryonic Stem Cell
Differentiation
Christoph Adams, Ph.D.,
Research Area Manager/Epigenetics, Life Sciences Division, Invitrogen
Corporation
Recent studies have indicated that miRNA, a class of
non-coding small RNA that participate in the regulation of gene expression,
may play a role in stem cell self renewal and differentiation. The NCodeTM
miRNA Labeling System, in conjunction with the NCodeTM Multi-Species
miRNA Microarray, provides a simple and quick screen of
miRNA populations in any given cell type. Using these analytical tools,
we profiled the global miRNA patterns between undifferentiated human embryonic
stem cells, 14 day-old embryoid bodies, and terminally differentiated cell
types and identified differentially expressed miRNAs that make useful markers
for stem cell staging.Understanding the pathways and mechanisms of miRNA-directed
epigenetic regulation of gene expression during the process of differentiation
in stem cells might allow for development of better tools to regulate this
process effectively.
11:35 A
High-Content MicroRNA Array for Analyzing the Expression of Verified and
Predicted Small, Non-Coding RNAs
Mike Wilson, Ph.D.,
Senior Scientist, Asuragen Services, Asuragen
We have designed a custom microRNA (miRNA) microarray that contains probes for
15,000 putative miRNAs selected from multiple sources, including the
Sanger miRBase database, published reports, and a proprietary database of
predicted miRNAs. We assessed the reproducibility, relative sensitivity, and
dynamic range of the platform, along with its concordance between two
alternative technologies. In addition to exhibiting excellent performance
characteristics, the array detected expression for many of the novel, putative
miRNAs in different tissues. In order to explore the relevance of this
platform for preclinical discovery of candidate diagnostic biomarkers and
therapeutic targets, we will analyze a collection of cancer tumors and normal
adjacent tissues. We expect to present this data that illustrates the
technological and biological utility of a custom, high-content miRNA
microarray for comprehensive expression profiling of novel miRNAs.
12:05 Clinical Implementation of a Targeted CGH-
Based Microarray for Detection of Chromosomal Abnormalities in 5000 Clinical
Cases
Sau W. Cheung, Ph.D.,
MBA, Director, Kleberg Cytogenetics Laboratory, Baylor College of Medicine
We report the outcome of array Comparative Genomic
Hybridization (aCGH) in 5000 consecutive cases for evaluation of individuals
with birth defects, dysmorphic features and mental retardation. The targeted
arrays consist of 853 FISH-verified BAC/PAC clones designed for detection of
>70 genomic disorders caused by microdeletion and duplications, as well as
detection of submicroscopic copy number changes in the 41 subtelomeric regions
and 43 pericentromeric regions known to be associated with mental retardation.
Overall, aCGH identified clinically relevant abnormalities in 9% patients and
copy number variations of uncertain significance in 9.6% of the patients. Of
the latter, over 80% were interpreted as familial variants.
aCGH in this large clinical cohort demonstrates improved sensitivity of
this technology for detection of clinical relevant genomic imbalances.
Detailed findings of these genomic imbalances, and examples of confirmatory
studies using whole genome oligoarray to further delineate the breakpoints of
these genomic imbalances will be presented.
12:35 Feed the Mind and the Body –
(Luncheon Seminar Sponsorship Available)
2:00
Novel Prognosis Prediction Model for Human Breast Cancer Patients Based
on a Heterologous Tissue Culture Gene Expression Signature
Eun Sung Park, Ph.D.,
Laboratory of Genetics, Center for Cancer Research, National Cancer Institute,
NIH
We developed mRNA expression based models that can predict
prognosis/outcomes of human breast cancer patients regardless of microarray
platform and patient group. Our model was developed using genes differentially
expressed in mouse plasma cell tumors growing in vivo versus those growing in
vitro. The prediction system was validated using published data from three
cohorts of patients for whom microarray and clinical data had been compiled
and proved to be a significantly improved survival predictor over other
expression-based models.
2:30
TBA
3:00
MIRA-Assisted Microarrays for Cancer Diagnosis
Tibor A. Rauch, Ph.D.,
Research Fellow, Beckman Research Institute, City of Hope National Medical
Center
The methylated-CpG island recovery assay (MIRA), which is
based on the high affinity of the MBD2/MBD3L1 complex for methylated DNA, has
been used to detect cancer-specific differences in DNA methylation on
microarray platforms. We demonstrated the feasibility of using MIRA in
combination with Affymetrix promoter arrays, NimbleGen genome tiling arrays
and Agilent CpG island arrays. MIRA-assisted microarray can provide the
opportunity for genome-wide analysis of DNA methylation patterns in human
cancers. Using this approach we identified early methylation markers for lung
squamous cell carcinoma.
3:30
Refreshment Break in Exhibit Hall
4:15
Molecular Diagnostics for Parkinson’s Disease Based on Gene
Expression in Blood
Clemens R. Scherzer,
M.D., Associate Neurologist, Center for Neurologic Diseases, Harvard Medical
School and Brigham and Women’s Hospital
We performed a transcriptome-wide scan in 105 individuals to
interrogate the molecular processes perturbed in cellular blood of patients
with early-stage PD. The molecular multigene marker here identified is
associated with risk of PD in 66 samples of the training set comprising
healthy and disease controls. It
is further validated in 39 independent test samples. Insights into
disease-linked processes detectable in peripheral blood are offered by 22
unique genes differentially expressed in patients with PD versus healthy
individuals. These include the co-chaperone ST13 that stabilizes heat shock
protein 70, a modifier of alpha-synuclein misfolding and toxicity. ST13
messenger RNA copies are lower in patients with PD than in controls in two
independent populations. Thus, gene expression signals measured in blood can
facilitate the development of biomarkers for PD.
4:45 Multiplex microRNA TaqMan®
Low Density Array: A High-Throughput Screening Tool for miRNA Profiling |
Sponsored by
 |
|
Yulei Wang, Ph.D., Gene Expression R&D, Applied Biosystems
We have developed TaqMan® miRNA Low Density Arrays to enable sensitive and specific genome-wide profiling. Highly sensitive and specific TaqMan® miRNA Assays targeting 369 human miRNAs and 16 endogenous controls are pre-loaded into a 384-well micro fluidic card. The reverse transcription step is performed in 48-plex and the cDNA loaded into the card for real-time PCR detection without the need for robotics. We will be presenting applications of this technology in screening biomarkers in clinical samples to identify patients at high-risk for recurrent thrombosis, and screening drug-resistant miRNA markers in the NCI60 cancer cell lines. |
|
5:00
Emerging Technologies and Platforms (Sponsorship
Available)
5:15
Development of Microarray Platform for Blood Screening
Dr. J. Petrik, Scottish
National Blood Transfusion Service & University of Edinburgh
Microarray technology offers a unifying platform for a variety
of assays performed currently in multiple formats. Blood grouping and pathogen
screening can be carried out by both, genotypic and phenotypic assays, but the
detection of antibodies against blood group antigens and pathogen antigens are
exclusively phenotypic assays. We have focused on the development of protein
microarrays as they can accommodate all types of assays required.
We have demonstrated successful protein – cell interaction blood
grouping microarray for ABO, Rh and some additional blood groups, as well as
direct antiglobulin test, using autofluorescent detection of bound
erythrocytes. In parallel, we are developing complementary antibody screen and
pathogen detection assays.
5:45
Networking Reception in Exhibit Hall
7:00
End of Day Two
