CBM.DIAGB.03.10.LLNL.007 Final Report

The purpose of this project was to construct a system for characterizing the threat potential of genomic sequences, specifically assembled draft genomes. New genomes are characterized by initially comparing them against already-sequenced genomes. If the new genome is determined to be from a high-threat species, detailed (forensic-level) characterization is done based on gene and SNP (Single Nucleotide Polymorphism) data comparisons with all other previously sequenced members of that high-threat species. New genomes are compared against a large set of known virulence and antibiotic-resistance genes and also compared against a large set of vectors that could be used for bacterial genetic engineering. Together, these analyses provide a comprehensive initial assessment of the most likely phylogenetic placement of a new genome, plus an assessment of the known-gene content and an indication of any possible bacterial genetic engineering utilizing vector-mediated techniques. This provides an initial threat potential summary based on high information content comparisons (e.g., thousands of genes, SNPs, and potential genetic engineering vectors) that can be used to guide subsequent operational response or more detailed laboratory characterization

Genetic Engineering Workshop Report, 2010

The Lawrence Livermore National Laboratory (LLNL) Bioinformatics group has recently taken on a role in DTRA's Transformation Medical Technologies (TMT) program. The high-level goal of TMT is to accelerate the development of broad-spectrum countermeasures. To achieve this goal, there is a need to assess the genetic engineering (GE) approaches, potential application as well as detection and mitigation strategies. LLNL was tasked to coordinate a workshop to determine the scope of investments that DTRA should make to stay current with the rapid advances in genetic engineering technologies, so that accidental or malicious uses of GE technologies could be adequately detected and characterized. Attachment A is an earlier report produced by LLNL for TMT that provides some relevant background on Genetic Engineering detection. A workshop was held on September 23-24, 2010 in Springfield, Virginia. It was attended by a total of 55 people (see Attachment B). Twenty four (44%) of the attendees were academic researchers involved in GE or bioinformatics technology, 6 (11%) were from DTRA or the TMT program management, 7 (13%) were current TMT performers (including Jonathan Allen and Tom Slezak of LLNL who hosted the workshop), 11 (20%) were from other Federal agencies, and 7 (13%) were from industries that are involved in genetic engineering. Several attendees could be placed in multiple categories. There were 26 attendees (47%) who were from out of the DC area and received travel assistance through Invitational Travel Orders (ITOs). We note that this workshop could not have been as successful without the ability to invite experts from outside of the Beltway region. This workshop was an unclassified discussion of the science behind current genetic engineering capabilities. US citizenship was not required for attendance. While this may have limited some discussions concerning risk, we felt that it was more important for this first workshop to focus on the scientific state of the art. We also consciously chose to not dwell on matters of policy (for example, screening of commercial gene or oligo synthesis orders), as multiple other forums for policy discussion have taken place in recent years. We acknowledge that other workshops on topics relevant to genetic engineering should be held, some of which may need to take place at higher classification levels. The workshop moderators would like to acknowledge the enthusiastic participation of the attendees in the discussions. Special thanks are given to Sofi Ibrahim, for his extensive assistance on helping this report reach its final form. The genetic engineering workshop brought together a diverse mix of genetic engineering pioneers and experts, Federal agency representatives concerned with abuses of genetic engineering, TMT performers, bioinformatics experts, and representatives from industry involved with large-scale genetic engineering and synthetic biology. Several talks established the current range of genetic engineering capabilities and the relative difficulties of identifying and characterizing the results of their use. Extensive discussions established a number of recommendations to DTRA of how to direct future research investments so that any mis-use of genetic engineering techniques can be promptly identified and characterized

Pancreatic cysts suspected to be branch duct intraductal papillary mucinous neoplasm without concerning features have low risk for development of pancreatic cancer.

BackgroundThe risk of developing pancreatic cancer is uncertain in patients with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD-IPMN) based on the "high-risk stigmata" or "worrisome features" criteria proposed in the 2012 international consensus guidelines ("Fukuoka criteria").MethodsRetrospective case series involving patients referred for endoscopic ultrasound (EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent with BD-IPMN. Rates of pancreatic cancer occurring at any location in the pancreas were compared between groups of patients with one or more Fukuoka criteria ("Highest-Risk Group", HRG) and those without these criteria ("Lowest-Risk Group", LRG).ResultsAfter exclusions, 661 patients comprised the final cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001).ConclusionsThis study supports using Fukuoka criteria to stratify the immediate and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of pancreatic cancer was highest during the first year and occurred exclusively in those with "high-risk stigmata" or "worrisome features" criteria. After the first year all BD-IPMN continued to have a low but persistent cancer risk

AS2TS system for protein structure modeling and analysis

We present a set of programs and a website designed to facilitate protein structure comparison and protein structure modeling efforts. Our protein structure analysis and comparison services use the LGA (local-global alignment) program to search for regions of local similarity and to evaluate the level of structural similarity between compared protein structures. To facilitate the homology-based protein structure modeling process, our AL2TS service translates given sequence–structure alignment data into the standard Protein Data Bank (PDB) atom records (coordinates). For a given sequence of amino acids, the AS2TS (amino acid sequence to tertiary structure) system calculates (e.g. using PSI-BLAST PDB analysis) a list of the closest proteins from the PDB, and then a set of draft 3D models is automatically created. Web services are available at

Spectral Properties of Holstein and Breathing Polarons

We calculate the spectral properties of the one-dimensional Holstein and breathing polarons using the self-consistent Born approximation. The Holstein model electron-phonon coupling is momentum independent while the breathing coupling increases monotonically with the phonon momentum. We find that for a linear or tight binding electron dispersion: i) for the same value of the dimensionless coupling the quasiparticle renormalization at small momentum in the breathing polaron is much smaller, ii) the quasiparticle renormalization at small momentum in the breathing polaron increases with phonon frequency unlike in the Holstein model where it decreases, iii) in the Holstein model the quasiparticle dispersion displays a kink and a small gap at an excitation energy equal to the phonon frequency w0 while in the breathing model it displays two gaps, one at excitation energy w0 and another one at 2w0. These differences have two reasons: first, the momentum of the relevant scattered phonons increases with increasing polaron momentum and second, the breathing bare coupling is an increasing function of the phonon momentum. These result in an effective electron-phonon coupling for the breathing model which is an increasing function of the total polaron momentum, such that the small momentum polaron is in the weak coupling regime while the large momentum one is in the strong coupling regime. However the first reason does not hold if the free electron dispersion has low energy states separated by large momentum, as in a higher dimensional system for example, in which situation the difference between the two models becomes less significant.Comment: 11 pages, 10 figure

FY11 Report on Metagenome Analysis using Pathogen Marker Libraries

Abstract not provide

Tools for Dissecting Supernova Remnants Observed with Chandra: Methods and Application to the Galactic Remnant W49B

We introduce methods to quantify the X-ray morphologies of supernova remnants observed with the Chandra X-ray Telescope. These include a power-ratio technique to measure morphological asymmetries, correlation-length analysis to probe chemical segregation and distribution, and wavelet-transform analysis to quantify X-ray substructure. We demonstrate the utility and accuracy of these techniques on relevant synthetic data. Additionally, we show the methods' capabilities by applying them to the 55-ks Chandra ACIS observation of the galactic supernova remnant W49B. We analyze the images of prominent emission lines in W49B and use the results to discern physical properties. We find that the iron morphology is very distinct from the other elements: it is statistically more asymmetric, more segregated, and has 25% larger emitting substructures than the lighter ions. Comparatively, the silicon, sulfur, argon, and calcium are well-mixed, more isotropic, and have smaller, equally-sized emitting substructures. Based on fits of XMM-Newton spectra in regions identified as iron rich and iron poor, we determine that the iron in W49B must have been anisotropically ejected. We measure the abundance ratios in many regions, and we find that large, local variations are persistent throughout the remnant. We compare the mean, global abundance ratios to those predicted by spherical and bipolar core-collapse explosions; the results are consistent with a bipolar origin from a 25 solar mass progenitor. We calculate the filling factor of iron from the volume of its emitting substructures, enabling more precise mass estimates than previous studies. Overall, this work is a first step toward rigorously describing the physical properties of supernova remnants for comparison within and between sources.Comment: 51 pages, 24 figures, accepted by ApJ. For full resolution figures, see http://www.astro.ucsc.edu/~lopez/paper.html Fixed typo in URL; no other change