Multifactor Dimensionality Reduction (MDR) Software

An important question in biodefense research is whether DNA sequence variations can predict who is at risk for adverse events following vaccination for bioterroism agents such as smallpox. We have developed and released a multifactor dimensionality reduction (MDR) software package for detecting and characterizing combinations of DNA sequence variations that predict complex clinical endpoints. The Dartmouth Computational Genetics Laboratory (CGL) is pleased to announce the release of MDR 0.3 with many new features. Information about the MDR method can be found here. The open-source MDR software package can be downloaded for free here.

Cost-effectiveness of defending against bioterrorism

A new study by Fowler et al. published in the Annals of Internal Medicine uses descision analytic models to determine the cost-effectiveness of defending against bioterrorism:

Fowler RA, Sanders GD, Bravata DM, Nouri B, Gastwirth JM, Peterson D, Broker AG, Garber AM, Owens DK. Cost-effectiveness of defending against bioterrorism: a comparison of vaccination and antibiotic prophylaxis against anthrax. Ann Intern Med. 2005 Apr 19;142(8):601-10. [PubMed]

Abstract:

BACKGROUND: Weaponized Bacillus anthracis is one of the few biological agents that can cause death and disease in sufficient numbers to devastate an urban setting. OBJECTIVE: To evaluate the cost-effectiveness of strategies for prophylaxis and treatment of an aerosolized B. anthracis bioterror attack. DESIGN: Decision analytic model. DATA SOURCES: We derived probabilities of anthrax exposure, vaccine and treatment characteristics, and their costs and associated clinical outcomes from the medical literature and bioterrorism-preparedness experts. TARGET POPULATION: Persons living and working in a large metropolitan U.S. city. TIME HORIZON: Patient lifetime. PERSPECTIVE: Societal. INTERVENTION: We evaluated 4 postattack strategies: no prophylaxis, vaccination alone, antibiotic prophylaxis alone, or vaccination and antibiotic prophylaxis, as well as preattack vaccination versus no vaccination. OUTCOME MEASURES: Costs, quality-adjusted life-years, life-years, and incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: If an aerosolized B. anthracis bioweapon attack occurs, postexposure prophylactic vaccination and antibiotic therapy for those potentially exposed is the most effective (0.33 life-year gained per person) and least costly (355 dollars saved per person) strategy, as compared with vaccination alone. At low baseline probabilities of attack and exposure, mass previous vaccination of a metropolitan population is more costly (815 million dollars for a city of 5 million people) and not more effective than no vaccination. RESULTS OF SENSITIVITY ANALYSIS: If prophylactic antibiotics cannot be promptly distributed after exposure, previous vaccination may become cost-effective. LIMITATIONS: The probability of exposure and disease critically depends on the probability and mechanism of bioweapon release. CONCLUSIONS: In the event of an aerosolized B. anthracis bioweapon attack over an unvaccinated metropolitan U.S. population, postattack prophylactic vaccination and antibiotic therapy is the most effective and least expensive strategy.

News and media from Sunnybrook & Women's.

Immunomics of category A-C pathogens

A new paper in Immunity discusses the NIAID Large-Scale Antibody and T Cell Epitope Discovery Program.

Sette A, Fleri W, Peters B, Sathiamurthy M, Bui HH, Wilson S. A roadmap for the immunomics of category A-C pathogens. Immunity. 2005 Feb;22(2):155-61. [PubMed]

Abstract:

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), recently awarded 14 contracts to fund the Large-Scale Antibody and T Cell Epitope Discovery Program. This initiative is designed to identify immune epitopes from selected infectious agents utilizing complementary methods for epitope discovery. NIAID will make information on each newly identified epitope freely available to scientists worldwide through the Immune Epitope Database and Analysis Resource (IEDB), currently under development. On October 12-14, 2004, representatives of NIAID met in San Diego, California, with a group of investigators from various research institutions to discuss progress and plans for the large-scale epitope discovery projects and for the establishment of the IEDB. It is anticipated that these initiatives will establish detailed maps of immune reactions toward several important complex pathogens, which in turn will foster development of new diagnostic, immune-based therapeutic, and vaccine programs. Herein is an account of the meeting and its results.

Poxvirus Bioinformatics Resource Center

The following paper in the database issue of Nucleic Acids Research describes the Poxvirus Bioinformatics Resource Center:

Lefkowitz EJ, Upton C, Changayil SS, Buck C, Traktman P, Buller RM. Poxvirus Bioinformatics Resource Center: a comprehensive Poxviridae informational and analytical resource. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D311-6. [PubMed]

Here is their website: www.poxvirus.org

Welcome!

Welcome to Biodefense Bioinformatics Blog. Starting today, the Dartmouth Computational Genetics Laboratory will be blogging on topics related to the computational analysis of biomedical data collected as part of biodefense research projects. This blog and our biodefense research is supported by a grant from the NIH/NIAID (AI59694, PI- Moore).