The Banbury Center Workshop

Cold Spring Harbor Laboratory
September 18-21, 2005

The Centers for Disease Control & Prevention (CDC) organized a meeting, From Markers to Models: Integrating Data to Make Sense of Biologic Systems, at the Banbury Center, Cold Spring Harbor Laboratory, Long Island, New York on September 18-21, 2005. The CFIDS Association of America cosponsored the meeting.

This meeting was the culmination of CDC's 6-month CFS Computational Challenge. The objective of the Challenge was to devise and utilize methods to integrate and interpret epidemiologic, clinical, and laboratory data gathered during the in-hospital clinical study of CFS that CDC conducted in 2003 in Wichita, Kansas.

The challenge began with a March 2005 meeting in Atlanta. Participants were organized into 4 teams, each with 6 investigators representing diverse research disciplines (medicine, molecular biology, mathematics, physics and engineering). Each team was provided the complete data set collected from the 227 clinical study subjects. The data set included demographic and clinical (medical and psychiatric) characteristics, quantitative assessments of participants' symptoms, evaluation of sleep characteristics and cognitive function, laboratory assays of immune and endocrine status, and gene expression profiles for 20,000 genes. In addition to the team participants, 10 experts in medicine and modeling were invited to present in their area of expertise and to critically evaluate the outcome of each team's effort.

The 4 teams used quite different strategies to attack the problem. The first team focused on empirically delineating the heterogeneity of chronic unexplained fatigue by using all data except that for gene expression. After empirically defining different clinical groups, they validated the different groups by using gene-expression profiling. The second team utilized the gene-expression data to help define the pathophysiology of the symptoms associated with chronic fatigue. They identified a gene-expression signature that is highly correlated with mental fatigue. The third team took a hypothesis-driven approach, exploring questions regarding physiologic markers of stress-burden (allostatic load) and gene-expression profiles.

Last, the fourth team used factor analysis to group the subjects into various fatigue groups and applied correspondence and cluster analyses to determine gene-expression correlates for each group.

Each team is finalizing their results and anticipates 2 to 3 papers from their challenge efforts. The editor of the journal Pharmacogenomics will be dedicating the April 2006 issue to these papers and those from the subject-matter experts.

Workshop Participants

• Gordon Broderick, PhD
  Institute for Biomolecular Design, University of Alberta, Canada
• Mark A. Demitrack, MD
  Neuronetics Inc, Malvern, PA
• Sol Efroni, PhD
  National Cancer Institute Center for Bioinformatics, Bethesda, MD
• Jennifer Fostel, PhD
  National Center for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, NC
• Ben Geortzel, PhD
  Biomind LLC, Columbia, MD
• Muin Khoury, MD
  Office of Public Health Genomics, CDC, Atlanta, GA
• Kimberly K. McCleary
  The CFIDS Association of America, Charlotte, NC
• Nancy Klimas, MD
  VA Medical Center, Miami, FL
• Simon M. Lin, MD
  Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
• Andrew Lloyd, MD
  Department of Infectious Diseases, University of New South Wales, Australia
• Andy Miller, MD
  Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA
• Bud Mishra, PhD
  Courant Institute of Mathematical Sciences, New York University, New York, NY
• Giuseppe Pagnoni, PhD
  Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA
• Jennifer Shoemaker, PhD
  Department of Biostatistics and Bioinformatics, Duke University, Durham, NC
• Joe DiStefano
  Departments of Computer Science, Medicine & Biomedical Engineering, University of California at Los Angeles, Los Angeles, CA
• Renee Taylor, PhD
  Department of Occupational Therapy, University of Illinois at Chicago, Chicago, IL
• Weida Tong, PhD
  Center for Toxicogenomics, FDA's National Center for Toxicological Research, Jefferson, AR
• Ute Vollmer-Conna, PhD
  Department of Human Behaviour, School of Psychiatry, University of New South Wales, Australia
• Peter White, MD
  Department of Psychological Medicine, Queen Mary School of Medicine and Dentistry, St Bartholomew's Hospital, London, UK
• Lingchong You, PhD
  Department of Biomedical Engineering, Duke University, Durham, NC

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CDC CFS Research Program Participants

• Eric Aslakson, MS
• Roumiana Boneva, MD
• Cameron Craddock, MS
• Brian Gurbaxani, PhD
• James F. Jones, MD
• Elizabeth Maloney, PhD
• Rajeevan Mangalathu, PhD
• William C. Reeves, MD, MSc
• Matthew Tiller, BS
• Elizabeth R. Unger, PhD, MD
• Suzanne D. Vernon, PhD
• Toni Whistler, PhD

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Agenda

From Markers to Models: Integrating Data to Make Sense of Biologic Systems

Monday (8:30a.m. to 5:30p.m.)

Session Chair: William C. Reeves

8:30 - 8:45

C3: CFS Computational Challenge (Suzanne D. Vernon, PhD)

8:45 - 9:30

Lessons Learned from 5 years of CAMDA (Simon M. Lin, MD)

9:30 - 10:30

Computational and Experimental Framework to Understand Disease Pathogenesis (Bud Mishra, PhD)

10:30 - 10:45

Break

10:45 - 12:00

Team 1: Towards the Nosology of Chronic Unexplained Fatigue:

1. Initial data perusal to direct hypothesis-driven analysis
2. Analytical approach
3. Results and biological interpretation

12:00 - 12:30

Discussion

12:30 - 2:00

Lunch

2:00 - 3:00

From Genomics to Health Outcomes: Integrating Complex Data for Medicine and Public Health (Muin Khoury, MD (Dr. Khoury could not attend))

3:00 - 4:00

Team 2: CFS: From Constructs to Mechanisms:

1. Initial data perusal to direct hypothesis-driven analysis
2. Analytical approach
3. Results and biological interpretation

4:00 - 4:15

Break

4:15 - 4:45

Mathematical and Statistical Challenges for High-Throughput Data (Jennifer Shoemaker, PhD)

4:45 - 5:45

Team 3: Challenges of Elucidating Pathophysiology in Complex Disorders:

1. Initial data perusal to direct hypothesis-driven analysis
2. Analytical approach
3. Results and biological interpretation

6:00

Dinner

Tuesday

Session Chair: Andy Miller

9:00-10:00

Clinical Perspectives on Therapeutic Interventions for CFS (Mark Demitrack, MD)

10:00-11:00

Dynamic Systems Modeling and Thyroid Hormone Regulation and Metabolism in Mammals (Joe DiStefano, PhD)

11:00-11:30

Break

11:30-12:30

Team 4: Bridging the Gap between the Neuroendocrine and Immune Systems

1. Initial data perusal to direct hypothesis-driven analysis
2. Analytical approach(es)
3. Results and biological interpretation

12:30-2:00

Lunch

2:00-4:00

Breakout session for non-C3 participants to evaluate and summarize team approach:

• Team 1: Bud Mishra and Mark Demitrack
• Team 2: Jennifer Shoemaker and Giuseppe Pagnoni
• Team 3: Simon Lin and William C. Reeves
• Team 4: Joe DiStefano and Andy Miller

4:00-4:30

Break

4:30-4:45

Report on Team 1 (Bud Mishra and Mark Demitrach)

4:45-5:00

Report on Team 2 (Jennifer Shoemaker and Giuseppe Pagnoni)

5:00-5:15

Report on Team 3 (Simon Lin and William C. Reeves)

5:15-5:30

Report on Team 4 (Joe DiStefano and Andy Miller, report on Team 4)

6:00

Dinner

Wednesday

9:00-11:30

Team breakout session

11:30-12:00

Next steps:

• Computational and Biologic Validation
• Publications

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