Genomic multiple sequence alignments: refinement using a genetic algorithm

BACKGROUND: Genomic sequence data cannot be fully appreciated in isolation. Comparative genomics – the practice of comparing genomic sequences from different species – plays an increasingly important role in understanding the genotypic differences between species that result in phenotypic differences as well as in revealing patterns of evolutionary relationships. One of the major challenges in comparative genomics is producing a high-quality alignment between two or more related genomic sequences. In recent years, a number of tools have been developed for aligning large genomic sequences. Most utilize heuristic strategies to identify a series of strong sequence similarities, which are then used as anchors to align the regions between the anchor points. The resulting alignment is globally correct, but in many cases is suboptimal locally. We describe a new program, GenAlignRefine, which improves the overall quality of global multiple alignments by using a genetic algorithm to improve local regions of alignment. Regions of low quality are identified, realigned using the program T-Coffee, and then refined using a genetic algorithm. Because a better COFFEE (Consistency based Objective Function For alignmEnt Evaluation) score generally reflects greater alignment quality, the algorithm searches for an alignment that yields a better COFFEE score. To improve the intrinsic slowness of the genetic algorithm, GenAlignRefine was implemented as a parallel, cluster-based program. RESULTS: We tested the GenAlignRefine algorithm by running it on a Linux cluster to refine sequences from a simulation, as well as refine a multiple alignment of 15 Orthopoxvirus genomic sequences approximately 260,000 nucleotides in length that initially had been aligned by Multi-LAGAN. It took approximately 150 minutes for a 40-processor Linux cluster to optimize some 200 fuzzy (poorly aligned) regions of the orthopoxvirus alignment. Overall sequence identity increased only slightly; but significantly, this occurred at the same time that the overall alignment length decreased – through the removal of gaps – by approximately 200 gapped regions representing roughly 1,300 gaps. CONCLUSION: We have implemented a genetic algorithm in parallel mode to optimize multiple genomic sequence alignments initially generated by various alignment tools. Benchmarking experiments showed that the refinement algorithm improved genomic sequence alignments within a reasonable period of time

SS-Wrapper: a package of wrapper applications for similarity searches on Linux clusters

BACKGROUND: Large-scale sequence comparison is a powerful tool for biological inference in modern molecular biology. Comparing new sequences to those in annotated databases is a useful source of functional and structural information about these sequences. Using software such as the basic local alignment search tool (BLAST) or HMMPFAM to identify statistically significant matches between newly sequenced segments of genetic material and those in databases is an important task for most molecular biologists. Searching algorithms are intrinsically slow and data-intensive, especially in light of the rapid growth of biological sequence databases due to the emergence of high throughput DNA sequencing techniques. Thus, traditional bioinformatics tools are impractical on PCs and even on dedicated UNIX servers. To take advantage of larger databases and more reliable methods, high performance computation becomes necessary. RESULTS: We describe the implementation of SS-Wrapper (Similarity Search Wrapper), a package of wrapper applications that can parallelize similarity search applications on a Linux cluster. Our wrapper utilizes a query segmentation-search (QS-search) approach to parallelize sequence database search applications. It takes into consideration load balancing between each node on the cluster to maximize resource usage. QS-search is designed to wrap many different search tools, such as BLAST and HMMPFAM using the same interface. This implementation does not alter the original program, so newly obtained programs and program updates should be accommodated easily. Benchmark experiments using QS-search to optimize BLAST and HMMPFAM showed that QS-search accelerated the performance of these programs almost linearly in proportion to the number of CPUs used. We have also implemented a wrapper that utilizes a database segmentation approach (DS-BLAST) that provides a complementary solution for BLAST searches when the database is too large to fit into the memory of a single node. CONCLUSIONS: Used together, QS-search and DS-BLAST provide a flexible solution to adapt sequential similarity searching applications in high performance computing environments. Their ease of use and their ability to wrap a variety of database search programs provide an analytical architecture to assist both the seasoned bioinformaticist and the wet-bench biologist

Bromodomains in Protozoan Parasites: Evolution, Function, and Opportunities for Drug Development

Parasitic infections remain one of the most pressing global health concerns of our day, affecting billions of people and producing unsustainable economic burdens. The rise of drug-resistant parasites has created an urgent need to study their biology in hopes of uncovering new potential drug targets. It has been established that disrupting gene expression by interfering with lysine acetylation is detrimental to survival of apicomplexan (Toxoplasma gondii and Plasmodium spp.) and kinetoplastid (Leishmania spp. and Trypanosoma spp.) parasites. As "readers" of lysine acetylation, bromodomain proteins have emerged as key gene expression regulators and a promising new class of drug target. Here we review recent studies that demonstrate the essential roles played by bromodomain-containing proteins in parasite viability, invasion, and stage switching and present work showing the efficacy of bromodomain inhibitors as novel antiparasitic agents. In addition, we performed a phylogenetic analysis of bromodomain proteins in representative pathogens, some of which possess unique features that may be specific to parasite processes and useful in future drug development

Orthopoxvirus Genome Evolution: The Role of Gene Loss

Poxviruses are highly successful pathogens, known to infect a variety of hosts. The family Poxviridae includes Variola virus, the causative agent of smallpox, which has been eradicated as a public health threat but could potentially reemerge as a bioterrorist threat. The risk scenario includes other animal poxviruses and genetically engineered manipulations of poxviruses. Studies of orthologous gene sets have established the evolutionary relationships of members within the Poxviridae family. It is not clear, however, how variations between family members arose in the past, an important issue in understanding how these viruses may vary and possibly produce future threats. Using a newly developed poxvirus-specific tool, we predicted accurate gene sets for viruses with completely sequenced genomes in the genus Orthopoxvirus. Employing sensitive sequence comparison techniques together with comparison of syntenic gene maps, we established the relationships between all viral gene sets. These techniques allowed us to unambiguously identify the gene loss/gain events that have occurred over the course of orthopoxvirus evolution. It is clear that for all existing Orthopoxvirus species, no individual species has acquired protein-coding genes unique to that species. All existing species contain genes that are all present in members of the species Cowpox virus and that cowpox virus strains contain every gene present in any other orthopoxvirus strain. These results support a theory of reductive evolution in which the reduction in size of the core gene set of a putative ancestral virus played a critical role in speciation and confining any newly emerging virus species to a particular environmental (host or tissue) niche

POEM: Pricing Longer for Edge Computing in the Device Cloud

Multiple access mobile edge computing has been proposed as a promising technology to bring computation services close to end users, by making good use of edge cloud servers. In mobile device clouds (MDC), idle end devices may act as edge servers to offer computation services for busy end devices. Most existing auction based incentive mechanisms in MDC focus on only one round auction without considering the time correlation. Moreover, although existing single round auctions can also be used for multiple times, users should trade with higher bids to get more resources in the cascading rounds of auctions, then their budgets will run out too early to participate in the next auction, leading to auction failures and the whole benefit may suffer. In this paper, we formulate the computation offloading problem as a social welfare optimization problem with given budgets of mobile devices, and consider pricing longer of mobile devices. This problem is a multiple-choice multi-dimensional 0-1 knapsack problem, which is a NP-hard problem. We propose an auction framework named MAFL for long-term benefits that runs a single round resource auction in each round. Extensive simulation results show that the proposed auction mechanism outperforms the single round by about 55.6% on the revenue on average and MAFL outperforms existing double auction by about 68.6% in terms of the revenue.Comment: 8 pages, 1 figure, Accepted by the 18th International Conference on Algorithms and Architectures for Parallel Processing (ICA3PP

Data-driven multi-objective optimisation of coal-fired boiler combustion systems

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Coal remains an important energy source. Nonetheless, pollutant emissions – in particular Oxides of Nitrogen (NOx) – as a result of the combustion process in a boiler, are subject to strict legislation due to their damaging effects on the environment. Optimising combustion parameters to achieve a lower NOx emission often results in combustion inefficiency measured with the proportion of unburned coal content (UBC). Consequently there is a range of solutions that trade-off efficiency for emissions. Generally, an analytical model for NOx emission or UBC is unavailable, and therefore data-driven models are used to optimise this multi-objective problem. We introduce the use of Gaussian process models to capture the uncertainties in NOx and UBC predictions arising from measurement error and data scarcity. A novel evolutionary multi-objective search algorithm is used to discover the probabilistic trade-off front between NOx and UBC, and we describe a new procedure for selecting parameters yielding the desired performance. We discuss the variation of operating parameters along the trade-off front. We give a novel algorithm for discovering the optimal trade-off for all load demands simultaneously. The methods are demonstrated on data collected from a boiler in Jianbi power plant, China, and we show that a wide range of solutions trading-off NOx and efficiency may be efficiently located.This work was supported by the Engineering and Physical Sciences Research Council, United Kingdom [Grant No.: EP/M017915/1], the National Natural Science Foundation of China [Grant Nos.: 61375078 and 61304211], and the China Scholarship Council

The protein kinase TOUSLED facilitates RNAi in Arabidopsis

RNA silencing is an evolutionarily conserved mechanism triggered by double-stranded RNA that is processed into 21- to 24-nt small interfering (si)RNA or micro (mi)RNA by RNaseIII-like enzymes called Dicers. Gene regulations by RNA silencing have fundamental implications in a large number of biological processes that include antiviral defense, maintenance of genome integrity and the orchestration of cell fates. Although most generic or core components of the various plant small RNA pathways have been likely identified over the past 15 years, factors involved in RNAi regulation through post-translational modifications are just starting to emerge, mostly through forward genetic studies. A genetic screen designed to identify factors required for RNAi in Arabidopsis identified the serine/threonine protein kinase, TOUSLED (TSL). Mutations in TSL affect exogenous and virus-derived siRNA activity in a manner dependent upon its kinase activity. By contrast, despite their pleiotropic developmental phenotype, tsl mutants show no defect in biogenesis or activity of miRNA or endogenous trans-acting siRNA. These data suggest a possible role for TSL phosphorylation in the specific regulation of exogenous and antiviral RNA silencing in Arabidopsis and identify TSL as an intrinsic regulator of RNA interferenc

The effect of health insurance reform on the number of cataract surgeries in Chongqing, China

<p>Abstract</p> <p>Background</p> <p>Cataracts are the leading cause of blindness in China, and poverty is a major barrier to having cataract surgery. In 2003, the Chinese government began a series of new national health insurance reforms, including the New Cooperative Medical Scheme (NCMS) and the Urban Resident Basic Health Insurance scheme (URBMI). These two programs, combined with the previously existing Urban Employee Basic Health Insurance (UEBMI) program, aimed to make it easier for individuals to receive medical treatment. This study reports cataract surgery numbers in rural and urban populations and the proportion of these who had health insurance in Chongqing, China from 2003 to 2008.</p> <p>Methods</p> <p>The medical records of a consecutive case series, including 14,700 eyes of 13,262 patients who underwent age-related cataract surgery in eight hospitals in Chongqing from January 1, 2003, to December 31, 2008, were analysed retrospectively via multi-stage cluster sampling.</p> <p>Results</p> <p>In the past six years, the total number of cataract surgeries had increased each year as had the number of patients with insurance. Both the number of surgeries and the number of insured patients were much higher in the urban group than in the rural group. The rate of increase in the rural group however was much higher than in the urban group, especially in 2007 and 2008. The odds ratios of having health insurance for urban vs. rural individuals were relatively stable from 2003 to 2006, but it decreased in 2007 and was significantly lower in 2008.</p> <p>Conclusions</p> <p>Health insurance appears to be an important factor associated with increased cataract surgery in Chongqing, China. With the implementation of health insurance, the number of Chongqing's cataract surgeries was increased year by year.</p