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Past Solicitations
BAA 12-04
Whole Genome Approach to Microbial Forensics (WGAMF)

The Homeland Security Act of 2002 (Public Law 107-296) states that DHS S&T will "support basic and applied homeland security research to promote revolutionary changes in technologies; advance the development, testing and evaluation, and deployment of critical homeland security technologies; and accelerate the prototyping and deployment of technologies that would address homeland security vulnerabilities." Pursuant to this mission the Chemical Biological Division (CBD) seeks technologies to prevent and defend against a chemical and biological attack. In addition, the division is charged with pursuing research to improve response and restoration, conduct threat risk assessments, and invest in bioforensics research and development. The focus of this BAA is in the area of bioforensics research. The threat of terrorist or criminal use of pathogenic organisms and their toxins remains of great concern in the United States. There are vulnerabilities and needs to perform microbial forensic analyses for attribution purposes in a rigorous scientific manner. As part of the effort to deter biological terrorism and strengthen the law enforcement response to such an act, Homeland Security Presidential Directive (HSPD) 10, "Biodefense for the 21st Century" established a dedicated central microbial forensic laboratory known as the National Bioforensics Analysis Center (NBFAC), as part of the Department of Homeland Security to provide bioforensics analysis of evidence associated with the event. The NBFAC operates in partnership with the Federal Bureau of Investigation (FBI), the lead investigative agency in acts of terrorism. This BAA seeks research in the following technical focus areas (TFAs) to support the missions of the NBFAC and FBI for evidentiary analysis and interpretation of results to support a criminal investigation. The ultimate goal of this joint mission is the capture, indictment, and prosecution of the perpetrator(s) of the biocrime or terrorist attack. The NBFAC has instituted a robust, operational molecular biology program with enhanced capabilities to conduct genomic analysis of biological threat agents. The Bioforensics Research and Development Program supports NBFAC operational threat agent identification and characterization through investments in microbial forensics research and next generation technologies to include molecular biology, genomic comparison techniques, genotyping assays and physical/chemical analysis of sample matrix to better understand the origin, evolutionary history, production method and dissemination mechanism associated with the malicious use of biological agents. Pursuant to this mission the Bioforensics R&D Program seeks technologies to achieve the following goals: 1) Development and application of mathematical models for statistical confidence measurements in metagenomic analysis 2) Development of a procedure to support the transfer of viral cDNA generated in a BSL-3/4 laboratory to BSL-2 laboratory for genomic analysis 3) Whole-genome sequencing to capture the global biodiversity of human, plant and animal pathogens (bacterial, viral and fungal) in support of microbial forensics analysis.

Topics

TFA-1 - Development and application of mathematical models for statistical confidence measurements in metagenomic analysis

Currently, it is difficult to assign confidence to the results of metagenomic analyses. For example, in metagenomic sequencing, what do a small number of reads that match a particular organism say about the probability that the organism is actually present in the sample? New methods are needed to assess the likelihood that an organism is present in a metagenomic sample and to provide confidence intervals on abundance estimates. Bioforensics R&D is looking to invest in the development and application of mathematical models for (1) estimating the likelihood of a genome being present in a metagenomic sample, and (2) the most likely composition of a metagenomic sample including a list of genomes and their relative abundance. The system should go beyond metagenomic classification to provide a statistically supported estimate of sample composition that could be used in a biothreat agent detection context. Detection calls should be made at the most detailed level possible (at least species, and potentially strain), so that pathogens may be differentiated from their non-pathogenic relatives. The proposed approach should be adaptable to a range of sequence lengths and error profiles (e.g. Illumina and PacBio), and be tailored for execution in a high-performance computing environment, favoring accuracy over computing resources. The proposed methods should assume sensitive alignments (e.g. BLAST) between all sequencing reads and the search database are available, and such data can be provided, if needed, by the genomics group at the NBFAC. All software developed should be made freely available to non-commercial users, preferably using an open-source license.

TFA-2 - Development of a procedure to support the transfer of viral cDNA generated in a BSL-3/4 laboratory to BSL-2 laboratory for genomic analysis

BSL-3/4 level (+) strand RNA viruses must be converted to cDNA prior to DNA sequencing in BSL-2 laboratories. However, the genomic RNA derived from those viruses remains infectious and is in many cases a Select Agent itself. Because of this, the cDNA must be treated to remove all remaining RNA and then it must be tested to ensure the absence of infectious RNA before transfer to a BSL-2 laboratory. The aim of this project would be to develop and validate an improved method for cDNA synthesis and subsequent (+) strand RNA removal. The method should produce cDNA of sufficient quality (not degraded into small fragments) and quantity for sequencing, and the method should decrease the time required to convert BSL-3/4 (+) strand RNA to cDNA, which can be handled in BSL-2 laboratories.

TFA-3 - Whole-genome sequencing to capture the global biodiversity of human, plant and animal pathogens (bacterial, viral and fungal) in support of microbial forensics analysis

The genome is the most specific signature of an organism and it can be used to unambiguously distinguish a particular organism from all others. Because of the ability to distinguish between closely related organisms, whole genome sequencing is particularly relevant to the field of microbial forensics. Whole genome sequencing holds great promise for forensic analysis in terms of accuracy in pathogen identification and characterization, but this approach is limited by the databases available for genome sequence comparisons. Some pathogens, such as Bacillus anthracis have many sequenced genomes available for comparison, but for other pathogens, whole genome sequences are either rare or not available in public databases. In addition, there is no accepted standard for capturing and archiving the genomes of contemporary pathogens as they emerge. A more comprehensive catalog of genomes is needed that covers the full diversity (phylogenetic, functional, spatial, and temporal) of pathogens, as well as a long-term strategy for sequencing and archiving the genomes of contemporary pathogens as they emerge.

Key Dates
Solicitation Open Date:
12/01/2011
White Paper Registration Deadline:
01/27/2012 04:30 PM ET
White Paper Submission Deadline:
01/27/2012 04:30 PM ET
Submission Deadline:
03/30/2012 04:30 PM ET


Amendments and Q&As
amendment icon Amendment # 3
Posted Date 12/20/11
Question and Answer Set 2

amendment icon Amendment # 2
Posted Date 12/20/11

amendment icon Amendment # 1
Posted Date 12/20/11
Question and Answer Set 1



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