LLNL Genomic Assessment: Viral and Bacterial Sequencing Needs for TMTI, Tier 1 Report
The Lawrence Livermore National Lab Bioinformatics group has recently taken on a role in DTRA's Transformation Medical Technologies Initiative (TMTI). The high-level goal of TMTI is to accelerate the development of broad-spectrum countermeasures. To achieve those goals, TMTI has a near term need to obtain more sequence information across a large range of pathogens, near neighbors, and across a broad geographical and host range. Our role in this project is to research available sequence data for the organisms of interest and identify critical microbial sequence and knowledge gaps that need to be filled to meet TMTI objectives. This effort includes: (1) assessing current genomic sequence for each agent including phylogenetic and geographical diversity, host range, date of isolation range, virulence, sequence availability of key near neighbors, and other characteristics; (2) identifying Subject Matter Experts (SME's) and potential holders of isolate collections, contacting appropriate SME's with known expertise and isolate collections to obtain information on isolate availability and specific recommendations; (3) identifying sequence as well as knowledge gaps (eg virulence, host range, and antibiotic resistance determinants); (4) providing specific recommendations as to the most valuable strains to be placed on the DTRA sequencing queue. We acknowledge that criteria for prioritization of isolates for sequencing falls into two categories aligning with priority queues 1 and 2 as described in the summary. (Priority queue 0 relates to DTRA operational isolates whose availability is not predictable in advance.) 1. Selection of isolates that appear to have likelihood to provide information on virulence and antibiotic resistance. This will include sequence of known virulent strains. Particularly valuable would be virulent strains that have genetically similar yet avirulent, or non human transmissible, counterparts that can be used for comparison to help identify key virulence or host range genes. This approach will provide information that can be used by structural biologists to help develop therapeutics and vaccines. We have pointed out such high priority strains of which we are aware, and note that if any such isolates should be discovered, they will rise to the top priority. We anticipate difficulty locating samples with unusual resistance phenotypes, in particular. Sequencing strategies for isolates in queue 1 should aim for as complete finishing status as possible, since high-quality initial annotation (gene-calling) will be necessary for the follow-on protein structure analyses contributing to countermeasure development. Queue 2 for sequencing determination will be more dynamic than queue 1, and samples will be added to it as they become available to the TMTI program. 2. Selection of isolates that will provide broader information about diversity and phylogenetics and aid in specific detection as well as forensics. This approach focuses on sequencing of isolates that will provide better resolution of variants that are (or were) circulating in nature. The finishing strategy for queue 2 does not require complete closing with annotation. This queue is more static, as there is considerable phylogenetic data, and in this report we have sought to reveal gaps and make suggestions to fill them given existing sequence data and strain information. In this report we identify current sequencing gaps in both priority queue categories. Note that this is most applicable to the bacterial pathogens, as most viruses are by default in queue 1. The Phase I focus of this project is on viral hemorrhagic fever viruses and Category A bacterial agents as defined to us by TMTI. We have carried out individual analyses on each species of interest, and these are included as chapters in this report. Viruses and bacteria are biologically very distinct from each other and require different methods of analysis and criteria for sequencing prioritization. Therefore, we will describe our methods, analyses and conclusions separately for each category.
- Research Organization:
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 971776
- Report Number(s):
- LLNL-TR-417549; TRN: US201006%%852
- Country of Publication:
- United States
- Language:
- English
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