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Affymetrix

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Covance

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Biophotonics

Cancer Biomarkers

Disease Markers

Current Drug Safety

Current Pharmacogenomics and Personalized Medicine

Current Proteomics

Proteome Sciences

biocenter 

Bentham Science

Biolexis

PharmCast

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Protein Biomarkers

 

Monday, September 29

3:00-4:00  Conference Registration

4:00-4:10  Welcoming Remarks from Conference Director
Julia Boguslavsky, Cambridge Healthtech Institute

Establishing Biomarker Utility

(Shared Session)

4:10-4:15 Chairperson’s Opening Remarks

4:15-4:40  Five Characteristics of a Biomarker to be Useful for Personalizing Medicine
Felix Frueh, Ph.D., Vice President, Research & Development, Personalized Medicine, Medco Health Solutions, Inc.

4:40-5:05  Biomarkers for What? Diagnostic, Prognostic or Predictive?
Sudhir Srivastava, Ph.D., Chief, Cancer Biomarkers Research Group, NIH National Cancer Institute
Biomarkers have been touted as a next frontier in the realm of personalized medicine. However, one has to be specific and clear about its intended use: Diagnostic, Prognostic, or Predictive? Each type has a different purpose. Each has to meet certain criteria to be fit for the purpose. Therefore, when discussing biomarkers, one must clearly state its targeted goal and population.

5:05-5:30  Building a Biomarker Information Pipeline and Enabling Translational and Personalized Medicine: Leveraging Industry Standards to Bring Omics Closer to Medicine
Martin D. Leach, Ph.D., Executive Director, Basic Research & Biomarker IT, Merck & Co., Inc.

5:30-6:30  Opening Reception in the Exhibit Hall

 

Tuesday, September 30

 

CONCURRENT SESSIONS:

Genomic Biomarkers  |  Protein Biomarkers  |  Metabolic Biomarkers  |  Biomarker Data Analysis 


 

Protein Biomarkers

Download the Protien Biomarkers PDF

 7:00          Registration Open 

7:30-8:15  Morning Coffee or Technology Workshops
(Sponsorship Available. Contact Ilana Schwartz at 781-972-5457 or ischwartz@healthtech.com.)

7:30 Breakfast Workshop Covance
Biological Variation Based Data Interpretation. Why Can This be of Value?
Gordon F. Kapke, Ph.D., Senior Director of Biomarker Services, Covance Central Laboratory Services
With the emphasis on biomarkers to improve drug development the question arises as how to interpret the data. The traditional clinical laboratory methodology for interpreting data involves the identification of the expected values (the normal range) and from this range defining the probably of disease or no disease (sensitivity and specificity).  The challenge in drug development is in monitoring the patient overtime while identifying if important changes have occurred in the biomarker values that indicate inappropriate toxicity or demonstrate appropriate efficacy. The use of the reference interval as a means of identifying toxicity or efficacy will be challenged and an alternative approached based embracing biological variation will be proposed.

Translation of Protein Biomarkers to Clinical Practice

8:30-8:35  Chairperson’s Opening Remarks

8:35-9:00  Targeted Discovery: From Troponin I to Albumin as Markers
Rebekah Gundry, Ph.D., Biological Chemistry and Biomedical Engineering, Johns Hopkins University
To be Announced

9:00-9:25  Creating a Reliable Proteomics Pipeline by Identifying and Addressing Roadblocks to the Clinic: The NCI Perspective
Henry Rodriguez, Ph.D., M.B.A., Director, Clinical Proteomic Technologies for Cancer, Office of Technology and Industrial Relations, Office of the Director, National Cancer Institute
Although proteomics technologies could address important problems in clinical cancer research, attempts to use proteomics approaches to discover cancer biomarkers in biofluids and tissues have been largely unsuccessful and have engendered considerable skepticism.  The NCI’s Clinical Proteomic Technologies for Cancer initiative (http://proteomics.cancer.gov) is designed to accelerate the transition of proteomics technologies from basic research tools to reliable and robust clinical research platforms. This presentation outlines a strategy for the advancement of clinical proteomic technologies that perform consistently across platforms, instruments and laboratories to facilitate biomarker discovery.

9:25-9:50  In Search of Proteomic Biomarkers for Multiple Sclerosis: The Challenges of Translating Early Candidate Discovery to a Panel of Validated Markers
Alexander Buko, Ph.D., Director, Analytical Biochemistry and Proteomics, Biogen Idec
Biomarkers for a neurodegenerative disease, such as Multiple Sclerosis (MS), should reflect the pathogenic processes of the disease.  However, the identification of relevant biomarkers for MS poses unique challenges. These challenges include a lack of availability of relevant tissues and animal models, the complexity and heterogeneity of the disease, and a lack of pathways for functional validation of candidate biomarkers. Mass-spectra based proteomic profiling has received widespread attention as a tool for biomarker discovery.  Proteomics is especially well suited for discovery of biomarkers in cerebrospinal fluid, brain, spinal column and plasma, tissues which one expects to see proteomic changes in MS. A major data-analytical challenge is evolving, which is the extremely high dimensionality of proteomic data from a variety of sample types, exacerbated when the sample size is small. Here, the unique challenges that neurological disorders such as MS introduce to biomarker discovery are described and how technological advances in proteomic methods, sample prep and bioinformatics are overcoming some of these obstacles and are driving the discovery of novel biomarkers.

9:50-10:15  Sponsored Presentation EMD Novagen
WideScreen™ Assays for the Multiplex Detection and Quantitation of Cell Signaling Proteins and Serum Biomarkers
Laura Juckem, Ph.D., R&D Senior Scientist, Multiplex Assays, EMD Chemicals, Novagen
Bead-based immunoassays allow multiplex analysis of 5-20 protein analytes from a single sample. This session will discuss select WideScreen™ Assays and their use in the characterization of cell signaling events and in the analysis of serum biomarkers. These assays include:
·Multiplex assays to analyze the expression and tyrosine phosphorylation status of several key receptor tyrosine kinases, enabling the profiling of protein kinase inhibitors in a cellular context.
·An assay that uses EpiTag™ Technology (Epitome Biosystems) for the simultaneous, multiplex quantitation of total and phosphorylated ERK pathway proteins in a single well.
·Highly validated and functionally defined serum biomarker panels developed in partnership with Rules Based Medicine.

10:15-11:10 Networking Coffee Break with Poster and Exhibit Viewing

 

Clinical Proteomics:
Translation to Molecular Diagnostics

11:10-11:35             Nanoscale Proteomic Analysis of Clinical Cancer Specimens
Dean W. Felsher, M.D., Ph.D., Associate Professor, Division of Oncology, Stanford University
We have developed a novel nanoscale proteomic method for the analysis of oncorpotein expression and phospyorylation in clinical specimens.  The methodology is highly sensitive, rapid and automated and can be used for the analysis of clinical specimens from fine needle aspirates, peripheral blood and frozen sections.  Our approach will be useful for interrogation of targeted therapeutics.

11:35-12:00             Mass Spectrometric Immunoassay in Biomarker Development
Randall W. Nelson, Ph.D., Research Professor, Director of the Molecular Biosignatures Analysis Unit, The Biodesign Institute, Arizona State University
Critical to using mass spectrometry platforms for biomarker development is the need to transcend from the general profiling of proteins to the targeting of specific panels of proteins. The value of such targeted approaches lies in the ability to differentiate microheterogeneity in the proteins under investigation (i.e., gene, translational and posttranslational modifications), and to generate data on only the specific molecular determinants relevant to the disease. This talk will focus on using targeted mass spectrometric immunoassays to investigate human plasma and urinary proteins in healthy and disease cohorts. Results illustrating the ability to detect low-level protein variants relevant to type 2 diabetes will be presented, and how these findings are subsequently used to develop advanced assays for disease diagnosis and monitoring.12:00-1:40               Luncheon Technology Showcases

An Automated and Streamlined Solution to Increase Productivity and Confidence in Microarray Studies
Speaker to be Announced, Affymetrix
This case study highlights the increase in productivity and confidence in microarray results for whole genome expression analysis using a microplate-based high throughput platform. The platform includes automated target preparation, an array processing instrument and complementary reagents that minimize hands-on time. Applications in drug discovery and development will be discussed.

Cancer DSA™ - Disease Focused Microarrays: A Platform for Biomarker Discovery and Validation, Optimised for Use with FFPE Tissue
Austin Tanney, Ph.D., Scientific Liaison Manager, Almac Diagnostics

WideScreen™ Assays for the Multiplex Detection and Quantitation of Cell Signaling Proteins and Serum Biomarkers
Laura Juckem, Ph.D., R&D Senior Scientist, Multiplex Assays, EMD Chemicals, Novagen
Bead-based immunoassays allow multiplex analysis of 5-20 protein analytes from a single sample. This session will discuss select WideScreen™ Assays and their use in the characterization of cell signaling events and in the analysis of serum biomarkers. These assays include:
·Multiplex assays to analyze the expression and tyrosine phosphorylation status of several key receptor tyrosine kinases, enabling the profiling of protein kinase inhibitors in a cellular context.
·An assay that uses EpiTag™ Technology (Epitome Biosystems) for the simultaneous, multiplex quantitation of total and phosphorylated ERK pathway proteins in a single well.
·Highly validated and functionally defined serum biomarker panels developed in partnership with Rules Based Medicine.


Protein Biomarkers for Patient Stratification

1:40-1:45  Chairperson’s Opening Remarks

1:45-2:10  Cell Signaling Pathway Biomarkers for Personalized Therapy
Emanuel F. Petricoin, Ph.D., Co-Director, Center for Applied Proteomics and Molecular Medicine, Professor of Life Sciences, George Mason University
Cell signaling proteins and phosphoproteins represent some of the most powerful biomarkers today because they are true theranostic molecules: they are the drug targets themselves and they can be used as a diagnostic to stratify patients for therapy. However, implementation of these markers at the bedside is very difficult due to lack of a facile technology that can rapidly measure hundreds of signaling events from a tiny tissue biopsy. The development of the Reverse Phase Protein Microarray has provided an enabling approach to elucidate the activity state of tissue cells from a variety of diseases and provides facile, multiplexed analysis of the signaling network from clinical material. Implementation of this technology along with a new type of tissue fixative that preserves signaling molecule activity in tissue is now ongoing, and case studies will be presented that highlight the use of this approach at the bedside today.

 2:10-2:35 Prospects of Serum Peptidome Patterns and Exopeptidase Activities to Monitor Cancer
Paul Tempst, Ph.D., Director, Protein Center, Member, Molecular Biology Program, Memorial Sloan-Kettering Cancer Center
Past studies have established distinctive serum peptidome patterns that seemed to correlate with clinically relevant outcomes. In one case, a limited subset of peptides that provided class discrimination between patients with different types of solid tumors sorted into a small number of sequence clusters, leading us to believe they’re simply surrogates for the real biomarkers: exopeptidase activities. We therefore developed blood-exopeptidase activity assays that bypass known sample collection and handling bias as well as variability in endogenous peptide precursor levels. A resulting test that uses artificial substrates, metabolite quantitation with non-degradable, isotopically labeled standards, plus multivariate statistical analysis, provided class prediction of cancer patients vs. controls with 94% sensitivity and 90% specificity. Activity analysis may lead to a fundamentally new approach to biomarker development.

2:35-3:00  Discovery of Protein Biomarkers in Clinical and Pre-Clinical Studies 
Joanna Hunter, Ph.D., Director, Protein Analysis, Caprion Proteomics
Global proteomic profiling using mass spectrometry has been applied in clinical and pre-clinical studies to identify markers of disease, as well as predictive and pharmacodynamic markers of drug efficacy and safety.  These types of biomarkers can be used to stratify patients.  As an example of such a study, the impact of drug treatment was assessed using plasma from Alzheimer’s disease patients, examining the effect of donepezil on the plasma proteome.  Alzheimer’s disease patients were distinguished from normal subjects, a portion of which were affected by the drug.  A second study will be presented that highlights the discovery of secreted protein biomarkers. In a prostate cancer study, Golgi were isolated from human prostate tumors and associated normal tissue.   Proteins that were up-regulated in the lumen of the Golgi from the tumor were identified and included most of the known prostate tumor secreted markers, including PSA, ACPP, KLK2 and MIF.  Additional up-regulated secreted proteins were identified and have been verified to be differentially modulated in the blood.

3:00-4:00 Networking Refreshment Break with Poster and Exhibit Viewing

 

Protein Biomarkers to Assess Drug Toxicity and Efficacy

4:00-4:25 Translational Biomarkers for Kidney Toxicity
Vishal S. Vaidya, Ph.D., Instructor in Medicine, Brigham & Women’s Hospital, Harvard Medical School
Drug-induced nephrotoxicity plays a major role in the high incidence and prevalence of kidney injury in both hospitalized and non-hospitalized patients, which in many circumstances can be prevented or at least minimized by effective predictive toxicity screening in preclinical drug development studies. The absence of sensitive, specific, reliable and reproducible renal injury biomarkers affects the evaluation of response to therapy and individual patient safety, especially dose monitoring decisions for important life saving drugs with potential inherent kidney toxicity risk. For the last 100 years there have been no accepted kidney injury biomarkers. The standard metrics such as serum creatinine and blood urea nitrogen are very insensitive and non-specific functional biomarkers. The urine has yielded the most promising markers for the early detection of acute kidney injury (AKI) and further characterization is anticipated, which will qualify these markers as useful tools for the earlier diagnosis, identification of mechanism of injury, and assessment of site and severity of injury. Hopefully, one or more of these biomarkers, either alone or in combination, will prove to be useful in facilitating early diagnosis, guiding targeted intervention and monitoring disease progression and resolution. Translational biomarkers have the potential to not only transform the way we do predictive nephrotoxicity assessment but also the way we diagnose and treat patients with AKI.

4:25-4:50  Vaccines, Biomarkers and Correlates of Protection
Mark T. Esser, Ph.D., Senior Research Fellow, Vaccines and Biologics Research, Merck Research Laboratories
Vaccine biomarker assays have been used historically to monitor disease incidence and prevalence, measure immune responses to natural infection or vaccination and to determine the duration of immunity.  This talk will discuss how multiplexed antibody biomarker assays are being implemented in the development, licensure and post-licensure surveillance of vaccines with a case study on GARDASIL™, Merck’s vaccine for the prevention of cervical cancer.

4:50-5:15  Use of Toxicity Biomarkers in Regulatory Review: An FDA Reviewer's Perspective
Thomas Papoian, Ph.D., D.A.B.T., Pharmacologist/Toxicologist, Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
During development of drug or biologic therapeutics, toxicities are often seen in treated animals that can have serious implications for human subjects if similar effects were to occur at therapeutic doses. In the majority of cases, such toxicities are clinically monitorable using established assessments, such as clinical signs or standard laboratory tests. However, situations are not uncommon in which the toxicities seen in animals are not easily monitorable in humans. This can occur when there is a lack of an appropriate validated biomarker to monitor a specific toxicity if and when it develops, thus preventing appropriate interventions in patients before serious or irreversible toxicity develops. Availability of validated biomarkers for specific toxicities can greatly assist the safety assessment process by regulatory reviewers, so that development of needed therapeutics can proceed in a safe manner. Potential use of validated biomarkers of toxicity in a regulatory setting will be discussed.

 

Wednesday, October 1

 7:00          Registration Open

 

7:30-8:15  Breakfast Presentation  Proteome Sciences
An integrated quantitiative mass spectrometric workflow for the discovery and validation of protein biomarkers using Tandem Mass Tags (TMT®).
Dr. Rainer Voegeli, Commercial Director, Proteome Sciences plc.
The establishment of highly specific and sensitive validation assays is a key task to transfer candidate biomarkers from discovery into validation studies. In response to the limited availability of ELISA’s, single and multiple reaction monitoring (SRM, MRM) is emerging as a highly selective and sensitive approach for the quantitation of proteins. Here we present an integrated workflow for discovery, assay development and validation studies which utilises chemical labelling by Tandem Mass Tags (TMT). In discovery mode up to six samples are labelled with different colours of TMT, mixed and subsequently analysed by Tandem Mass Spectrometry in a single assay run. From individual samples generally >1,000 peptides and proteins are analysed.Peptides and proteins are selected as candidates for validation if they appear differentially regulated, and meet appropriate biostatistical properties across an adequately powered discovery study. Assay development is then performed using peptides unique to the candidate biomarkers. By combining MRM with peptide labelling by Tandem Mass Tags TMTzero (label mass: 224 Da) and sample labelling by TMTsixplex (label mass: 229 Da), peptide pairs are generated which exhibit perfect co-elution and show a mass difference of 5 Da per added Tag. Quantitation against a reference labelled with TMTzero is so made possible whilst maintaining the selectivity/specificity of MRM combined with the superior sensitivity of Triple Quadrupole instrumentation. This approach allows the very fast transfer of discovery candidates into high quality assays and alleviates the need for immunoassay development or the synthesis of heavy-isotope labelled peptides (as routinely used in MRM’s).

  1. Seamless transition from discovery to high quality, high sensitivity assay development will shorten validation time
  2. Multiplex Assay Capability is in-line with the expected multitude of biomarkers to be validated
  3. No need to invest into lengthy immunoassay-development prior to validation of the marker itself
  4. Quick translation from pre-clinical to human trials

 

 

Post-Translational Modifications as Biomarkers

8:30-8:35  Chairperson’s Opening Remarks

8:35-9:00  Expressed Prostatic Secretions as a Source of Glycoprotein Biomarkers for Prostate Cancer
O. John Semmes, Ph.D., Anthem Professor for Cancer Research; Director, Center for Biomedical Proteomics, Eastern Virginia Medical School
Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are glycoproteins secreted by prostate epithelial cells, and have a long clinical history of use as biomarkers of prostate cancers. These two proteins and many other prostatic-derived proteins are present at high concentrations in expressed prostatic secretions (EPS) in urine following a digital rectal exam prostate massage.  We have identified over 600 hundred proteins in these fluids, many of which represent secreted prostate glycoproteins.  Using PSA and PAP as models, the specific changes in their glycan structures associated with prostatic disease is being assessed using MALDI, ESI-TRAP and triple quadropole mass spectrometry approaches.  Identifying specific glycan changes can also be adapted to lectin ELISA based detection strategies.  Methods developed for characterization of PSA and PAP are readily adapted to the many other potential biomarker candidates present in the EPS fluids. Use of proximal prostate fluids like EPS represents a paradigm shift for prostate cancer biomarker strategies away from the traditional serum or tissue based sources and focuses on developing diagnostic assays based on the well described changes in carbohydrate expression of surface and secreted glycoproteins associated with the cancer phenotype.

9:00-9:25  Top Down Disease Proteomics for Protein Biomarker Discovery and Validation
Ying Ge, Ph.D., Director of Mass Spectrometry, Human Proteomics Program, School of Medicine and Public Health, University of Wisconsin-Madison
Top down disease proteomics extends top down proteomic technologies to study changes in proteins and protein complexes that lead to the dysfunction characteristic of disease. Common co- and post-translational modifications (PTM) can alter physical and chemical property, stability, activity and function of the protein. Aberrant modifications such as oxidation and hyper-phosphorylation are believed to be one of the underlying mechanisms for many human diseases, notably heart disease and cancer. Analysis of intact proteins (the “top down” approach) has great advantages in assessing point mutation and post-translational modifications, but has been largely ignored in modern proteomics mainly due to the difficulties in protein sample handling, the requirement for costly high end mass spectrometers, technical expertise to operate them, and the lack of automation and high throughput. Herein we are developing and applying top down methodologies to examine intact proteins extracted from both diseased and healthy human tissues and fluids to discover, characterize, and validate disease biomarkers. 

9:25-9:50  Label-Free Detection of Enzyme Activities with Self-Assembled Monolayer Desorption Ionization Time-Of-Flight Mass Spectrometry (SAMDI-TOF MS)
Steven M. Patrie, Ph.D., Assistant Professor, Division of Translational Research, Department of Internal Medicine, University of Texas-Southwestern Medical Center
We have previously shown that diverse protein and PTM-biomarkers can be rapidly isolated from humoral fluids with SAM-based immunosensors followed by characterization with SAMDI-TOF MS. This report expands the utility of our SAMDI approach to enzyme activity assays. We show optimal processing of immobilized protein and peptide substrates by endogenous enzymes present in humoral fluids. We will further apply the SAMDI approach to characterize clinically relevant enzyme activities in autoimmune disorders where protease activities perpetuate the immunological response.

 

Development Considerations for Single-Analyte Markers, Panels, and Profiles

 

10:50-11:15             Optimal Biomarker Approach: Data Analysis Considerations of Individual, Panel or Profile
Stephen Naylor, Ph.D., Chief Executive Officer & Chairman, PPM, Inc.
The advent of relatively high throughput and broad analyte coverage analysis in “omic” measurements has reignited a debate about what constitutes the optimal biomarker solution. Is it a single analyte per biological event, or a panel (3-10 analytes) or even a profile (>20 analytes)? This will be discussed in the context of statistical and data analysis as well as data mining characteristics.

11:15-11:40             Panel Discussion

11:40-1:10 Luncheon Technology Workshopmsc
Enabling Drug Development Through Multiplexed Assays
Monica Errico, Ph.D., Application Scientist, Scientific Services, Meso Scale Discovery
Meso Scale Discovery (MSD) has an electrochemiluminescence platform that is fast (1-3 minutes per plate independent of plate density), robust (non-fluidics instrument), radioactive free, sensitive (detection limits near 10 attomoles) and has a wide dynamic range (5 logs) with multiplexing capabilities. The performance (sensitivity, reproducibility, and ease of use) of multiplexing cytokines, cell signaling pathways, and multiplexed toxicology biomarkers assays will be presented. Development of multiplex panels for complex matrices is challenging because of varying levels of biomarkers, interfering substances in the sample, and interactions between proteins measured. The platform allows for simple assay development that can greatly reduce the amount of time to develop novel assays.  The combined properties of the system provide both a cost and time savings with a highly quantitative assay format while improving productivity.

11:40-1:10               Luncheon Technology WorkshopNext Gen Sciences
Multiplexed Biomarker Assay Development
Michael Pisano, Ph.D., President and CEO, NextGen Sciences
Biomarkerexpress™ is a suite of mass spectrometry-based biomarker services that utilize proprietary methods to significantly decrease timelines and increase the success rates traditionally associated with biomarker development.   The services include discovery of protein biomarkers, development of protein biomarker assays, testing biological samples utilizing the assays to determine levels of protein biomarkers.
Case Study 1: Discovery and Assay Development for Putative Biomarkers of Lung Cancer Progression
Case Study 2: Assay Development for a Panel of 30 Biomarkers for Alzheimer’s Disease 

 

 

 

Bridging Silos: Integrating Omic Data

(Shared Session)

1:10-1:15  Chairperson’s Opening Remarks

1:15-1:40  Integration of Metabolic and Transcriptomic Profiling for Understanding of Diabetes and Obesity Mechanisms
Christopher B. Newgard, Ph.D., Director, Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center
Type 2 diabetes is a disease that occurs as a result of metabolic dysfunction in multiple tissues, including most prominently liver, skeletal muscle, and the pancreatic islets of Langerhans.  An understanding of the transcriptional and metabolic networks that control normal functions in these tissues, and identification of the network elements that are perturbed during development of type 2 diabetes, are essential steps in the development of new therapies for the disease.  The value of targeted mass spectrometry-based profiling of key clusters of intermediary metabolites for identifying specific network perturbations will be highlighted, as will recent examples of integration of metabolomic and transcriptomic profiling for identifying heretofore unrecognized regulatory pathways.

1:40-2:05  Integrating Gene and Protein Expression Biomarkers in a Systems Biology Approach to Colon Cancer
Mark R. Chance, Ph.D., Director, Case Center for Proteomics; Director, Center for Synchrotron Biosciences; Professor, Department of Physiology & Biophysics, Case Western Reserve University
Protein interaction networks are at the heart of functional control of human disease. Network and pathway modeling driven by Omics based approaches are increasingly important to our understanding of disease progression and drug responses. However, deriving and validating network models are complex research problems requiring integra tion of multiple types of high-throughput data. We have recently employed a systems biology approach to find small networks of proteins discriminative of late stage human colorectal cancer (CRC). Expression proteomics studies were initially used to identify proteins differentially regulated when comparing normal and late stage tumor tissues obtained from adequately sized cohorts of human patients. Proteins identified by these experiments were used to seed a search for protein-protein interaction networks selective for biological relevance to the human colon.  We chose four significant networks returned by this search and illustrated using measures of mutual information, calculated using gene expression data, that certain protein “signatures” within each network are highly discriminative of late stage cancer versus control. These signatures would not have been discovered using only proteomic data, or by merely clustering the gene expression data. Expanding these signatures by a single hop generated four sub-networks, which were analyzed for biological relevance to human CRC. A number of the proteins in these sub-networks have been shown to be critically involved in the progression of CRC. Others have been recently identified as potential markers of CRC, and still others merit follow-on experimental validation for biological significance in this disease. This general approach can be applied to network modeling for a number of diseases.

2:05-2:30  A Systems Biology Approach to Biomarker Discovery
Karin Rodland, Ph.D., Science Lead for NIH Programs, Pacific Northwest National Laboratory
Efforts to identify biomarkers for early diagnosis or prognosis of cancer and other disease have often focused on a singular molecular species, with preference given to mRNA, microRNA, proteins, autoantibodies or metabolites based on available technologies and model systems. Each one of these measurements provides a snapshot of cell function, but a dynamic understanding of disease processes really requires the integration of all these modalities to the extent possible.  Particularly in the context of using biomarkers to guide therapeutic interventions, it is necessary to understand the relationship between changes in expression, and changes in function. One aspect of systems biology is the integration of heterogeneous datasets to define relationships that predict function. This talk will describe the application of this approach to models of chronic obstructive pulmonary disease.

2:30-2:55  Connecting the Biomarker Dots in Cancer and Neurodegenerative Diseases
Ira L. Goldknopf, Ph.D., Director, Proteomics, Power3 Medical Products, Inc.
The application of fundamental principles to Omic integration to address unmet clinical needs will be illustrated with examples from cancer and neurodegenerative diseases. The integrations relate analytical with clinical validation across different analytical processes and platforms; clinical diagnostics with assessment of severity, disease progression, and efficacy; and data analysis integrating proteomic and genomic biomarkers, post-translational modifications, and protein isoforms. The clinical applications cover testing of blood serum for early detection of breast cancer as well as for early differential diagnosis and monitoring of the neurodegenerative diseases. The attainment of biological significance in terms of monitoring mechanisms of disease through blood testing as well as practical clinical diagnostic applications of such testing will also be discussed.

3:00          Close of Conference