Compressing DNA sequence databases with coil

Background: Publicly available DNA sequence databases such as GenBank are large, and are growing at an exponential rate. The sheer volume of data being dealt with presents serious storage and data communications problems. Currently, sequence data is usually kept in large "flat files," which are then compressed using standard Lempel-Ziv (gzip) compression – an approach which rarely achieves good compression ratios. While much research has been done on compressing individual DNA sequences, surprisingly little has focused on the compression of entire databases of such sequences. In this study we introduce the sequence database compression software coil. Results: We have designed and implemented a portable software package, coil, for compressing and decompressing DNA sequence databases based on the idea of edit-tree coding. coil is geared towards achieving high compression ratios at the expense of execution time and memory usage during compression – the compression time represents a "one-off investment" whose cost is quickly amortised if the resulting compressed file is transmitted many times. Decompression requires little memory and is extremely fast. We demonstrate a 5% improvement in compression ratio over state-of-the-art general-purpose compression tools for a large GenBank database file containing Expressed Sequence Tag (EST) data. Finally, coil can efficiently encode incremental additions to a sequence database. Conclusion: coil presents a compelling alternative to conventional compression of flat files for the storage and distribution of DNA sequence databases having a narrow distribution of sequence lengths, such as EST data. Increasing compression levels for databases having a wide distribution of sequence lengths is a direction for future work

Model evaluation of target product profiles of an infant vaccine against respiratory syncytial virus (RSV) in a developed country setting

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in children worldwide and is a significant cause of hospital admissions in young children in England. No RSV vaccine has been licensed but a number are under development. In this work, we present two structurally distinct mathematical models, parameterized using RSV data from the UK, which have been used to explore the effect of introducing an RSV paediatric vaccine to the National programme. We have explored different vaccine properties, and dosing regimens combined with a range of implementation strategies for RSV control. The results suggest that vaccine properties that confer indirect protection have the greatest effect in reducing the burden of disease in children under 5 years. The findings are reinforced by the concurrence of predictions from the two models with very different epidemiological structure. The approach described has general application in evaluating vaccine target product profiles

The Role of Starbursts in the Formation of Galaxies & Active Galactic Nuclei

Starbursts are episodes of intense star-formation in the central regions of galaxies, and are the sites of roughly 25% of the high-mass star-formation in the local universe. In this contribution I review the role starbursts play in the formation and evolution of galaxies, the intergalactic medium, and active galactic nuclei. Four major conclusions are drawn. 1) Starburst galaxies are good analogues (in fact, the only plausible local analogues) to the known population of star-forming galaxies at high-redshift. 2) Integrated over cosmic time, supernova-driven galactic-winds (`superwinds') play an essential role in the evolution of galaxies and the inter-galactic medium. 3) Circumnuclear starbursts are an energetically-significant component of the Seyfert phenomenon. 4) The evolution of the population of the host galaxies of radio-quiet quasars is significantly different than that of powerful radio galaxies, and is at least qualitatively consistent with the standard picture of the hierarchical assembly of massive galaxies at relatively late times.Comment: 16 pages, 4 figures, Royal Society discussion meeting `The formation of galaxies

A Strategy to Reengineer the Meta Church Structure of Washington Cathedral to Better Incarnate the Gospel

The goal of this study was to assist Washington Cathedral in overcoming institutional entropy by presenting a strategy to systematically change the meta church’s incarnational organizations through a methodical, cathedral-wide process learned from the collaborative method displayed in the book of Acts. It is argued that the book of Acts presents an ever-growing and ever-changing model of the church. Accordingly, to overcome institutional entropy and resistance to change within an organization, continual growth and change are necessary for every healthy church. A fresh study of the church in Acts reveals a collaborative method that leadership can use to respond to conflict and resistance with positive change. Such a collaborative method has been designed for the meta church at Washington Cathedral, which is made up of home churches called Tiny Little Churches; diverse cultural congregations; and five nonprofit foundations ministering to the hurts of the world in the name of Jesus. To implement this method, a systematic, cathedral-wide plan for a yearly reengineering of ministries has been designed and is presented in this paper. Additionally, to gain a deeper understanding of the cultural context of Washington Cathedral, a careful demographic study of the area was completed and is presented in this paper. This study included interviews with demographers, pastors of the largest churches in the area, and political leaders of King County and the city of Redmond. Also included is an analysis of how the high-tech culture of this area impacted the creation of the meta church. This study presents a biblically sound and culturally relevant strategy that can be presented to the leadership of Washington Cathedral for continually improving the design of the meta church. It provides a plan to develop leadership that fulfills the mission of the meta church. The paper reflects careful study based upon Acts, and establishes and communicates information necessary to deepen the commitment of Washington Cathedral to its unique calling. Theological Mentor: Kurt Fredrickson, DMi

Outcomes of the 2013 GTO Workshop on Geothermal Code Comparison

Pacific Northwest National Laboratory (PNNL) is supporting the Department of Energy (DOE) Geothermal Technologies Office (GTO) in organizing and executing a model comparison activity. This project is directed at testing, diagnosing differences, and demonstrating modeling capabilities of a worldwide collection of numerical simulators for evaluating geothermal technologies. A key element of the projct was the planning and implementation of a one-day project kickoff workshop, held February 14, 2013 in Palo Alto, CA. The primary goals of the workshop were to 1) introduce the project and its objectives to potential participating team members, and 2) develop an initial set of test problem descriptions for use in the execution stage. This report summarizes the outcomes of the workshop

Computer aided manual validation of mass spectrometry-based proteomic data

Advances in mass spectrometry-based proteomic technologies have increased the speed of analysis and the depth provided by a single analysis. Computational tools to evaluate the accuracy of peptide identifications from these high-throughput analyses have not kept pace with technological advances; currently the most common quality evaluation methods are based on statistical analysis of the likelihood of false positive identifications in large-scale data sets. While helpful, these calculations do not consider the accuracy of each identification, thus creating a precarious situation for biologists relying on the data to inform experimental design. Manual validation is the gold standard approach to confirm accuracy of database identifications, but is extremely time-intensive. To palliate the increasing time required to manually validate large proteomic datasets, we provide computer aided manual validation software (CAMV) to expedite the process. Relevant spectra are collected, catalogued, and pre-labeled, allowing users to efficiently judge the quality of each identification and summarize applicable quantitative information. CAMV significantly reduces the burden associated with manual validation and will hopefully encourage broader adoption of manual validation in mass spectrometry-based proteomics.National Institutes of Health (U.S.) (Grant R24DK090963)National Institutes of Health (U.S.) (Grant U54CA112967)National Cancer Institute (U.S.). Integrative Cancer Biology Program (Fellowship)Charles S. Krakauer FellowshipHugh Hampton Young Fellowshi

Routine fixation of humeral shaft fractures is cost-effective:cost-utility analysis of 215 patients at a mean of five years following nonoperative management

Aims: The primary aim was to estimate the cost-effectiveness of routine operative fixation for all patients with humeral shaft fractures. The secondary aim was to estimate the health economic implications of using a Radiographic Union Score for HUmeral fractures (RUSHU) of < 8 to facilitate selective fixation for patients at risk of nonunion. Methods: From 2008 to 2017, 215 patients (mean age 57 yrs (17 to 18), 61% female (n = 130/215)) with a nonoperatively managed humeral diaphyseal fracture were retrospectively identified. Union was achieved in 77% (n = 165/215) after initial nonoperative management, with 23% (n = 50/215) uniting after surgery for nonunion. The EuroQol five-dimension three-level health index (EQ-5D-3L) was obtained via postal survey. Multiple regression was used to determine the independent influence of patient, injury, and management factors upon the EQ-5D-3L. An incremental cost-effectiveness ratio (ICER) of < £20,000 per quality-adjusted life-year (QALY) gained was considered cost-effective. Results: At a mean of 5.4 yrs (1.2 to 11.0), the mean EQ-5D-3L was 0.736 (95% confidence interval (CI) 0.697 to 0.775). Adjusted analysis demonstrated the EQ-5D-3L was inferior among patients who united after nonunion surgery (β = 0.103; p = 0.032). Offering routine fixation to all patients to reduce the rate of nonunion would be associated with increased treatment costs of £1,542/patient, but would confer a potential EQ-5D-3L benefit of 0.120/patient over the study period. The ICER of routine fixation was £12,850/QALY gained. Selective fixation based on a RUSHU < 8 at six weeks post-injury would be associated with reduced treatment costs (£415/patient), and would confer a potential EQ-5D-3L benefit of 0.335 per ‘at-risk patient’. Conclusion: Routine fixation for patients with humeral shaft fractures to reduce the rate of nonunion observed after nonoperative management appears to be a cost-effective intervention at five years post-injury. Selective fixation for patients at risk of nonunion based on their RUSHU may confer even greater cost-effectiveness, given the potential savings and improvement in health-related quality of life. Cite this article: Bone Jt Open 2022;3(7):566–572