BACKGROUND: The field of metagenomics (study of genetic material recovered directly from an environment) has grown rapidly, with many bioinformatics analysis methods being developed. To ensure appropriate use of such methods, robust comparative evaluation of their accuracy and features is needed. For taxonomic classification of sequence reads, such evaluation should include use of clade exclusion, which better evaluates a method's accuracy when identical sequences are not present in any reference database, as is common in metagenomic analysis. To date, relatively small evaluations have been performed, with evaluation approaches like clade exclusion limited to assessment of new methods by the authors of the given method. What is needed is a rigorous, independent comparison between multiple major methods, using the same in silico and in vitro test datasets, with and without approaches like clade exclusion, to better characterize accuracy under different conditions. RESULTS: An overview of the features of 38 bioinformatics methods is provided, evaluating accuracy with a focus on 11 programs that have reference databases that can be modified and therefore most robustly evaluated with clade exclusion. Taxonomic classification of sequence reads was evaluated using both in silico and in vitro mock bacterial communities. Clade exclusion was used at taxonomic levels from species to class-identifying how well methods perform in progressively more difficult scenarios. A wide range of variability was found in the sensitivity, precision, overall accuracy, and computational demand for the programs evaluated. In experiments where distilled water was spiked with only 11 bacterial species, frequently dozens to hundreds of species were falsely predicted by the most popular programs. The different features of each method (forces predictions or not, etc.) are summarized, and additional analysis considerations discussed. CONCLUSIONS: The accuracy of shotgun metagenomics classification methods varies widely. No one program clearly outperformed others in all evaluation scenarios; rather, the results illustrate the strengths of different methods for different purposes. Researchers must appreciate method differences, choosing the program best suited for their particular analysis to avoid very misleading results. Use of standardized datasets for method comparisons is encouraged, as is use of mock microbial community controls suitable for a particular metagenomic analysis.

MOTIVATION: PSORTb has remained the most precise bacterial protein subcellular localization (SCL) predictor since it was first made available in 2003. However, the recall needs to be improved and no accurate SCL predictors yet make predictions for archaea, nor differentiate important localization subcategories, such as proteins targeted to a host cell or bacterial hyperstructures/organelles. Such improvements should preferably be encompassed in a freely available web-based predictor that can also be used as a standalone program. RESULTS: We developed PSORTb version 3.0 with improved recall, higher proteome-scale prediction coverage, and new refined localization subcategories. It is the first SCL predictor specifically geared for all prokaryotes, including archaea and bacteria with atypical membrane/cell wall topologies. It features an improved standalone program, with a new batch results delivery system complementing its web interface. We evaluated the most accurate SCL predictors using 5-fold cross validation plus we performed an independent proteomics analysis, showing that PSORTb 3.0 is the most accurate but can benefit from being complemented by Proteome Analyst predictions. AVAILABILITY: http://www.psort.org/psortb (download open source software or use the web interface). CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

UNLABELLED: As the genome sequences of multiple strains of a given bacterial species are obtained, more generalized bacterial genome databases may be complemented by databases that are focused on providing more information geared for a distinct bacterial phylogenetic group and its associated research community. The Burkholderia Genome Database represents a model for such a database, providing a powerful, user-friendly search and comparative analysis interface that contains features not found in other genome databases. It contains continually updated, curated and tracked information about Burkholderia cepacia complex genome annotations, plus other Burkholderia species genomes for comparison, providing a high-quality resource for its targeted cystic fibrosis research community. AVAILABILITY: http://www.burkholderia.com. Source code: GNU GPL.

The SSAPRE algorithm for performing partial redundancy elimination based entirely on SSA form is presented. The algorithm is formulated based on a new conceptual framework, the factored redundancy graph, for analyzing redundancy, and representes the first sparse approach to the classical problem and on methods for its solution. With the algorithm description, theorems and their proofs are given showing that the algorithm produces the best possible code by the criteria of computational optimality and lifetime optimality of the introduced temporaries. In addition to the base algorithm, a practical implementation of SSAPRE that exhibits additional compile-time efficiencies is described. In closing, measurement statistics are provided that characterize the instances of the partial redundancy problem from a set of benchmark programs and compare optimization time spent by an implementation of SSAPRE aganist a classical partial redundancy elimination implementation. The data lend insight into the nature of partial redundancy elimination and demonstrate the expediency of this new approach.

An algorithm for register promotion is presented based on the observation that the circumstances for promoting a memory location’s value to register coincide with situations where the program exhibits partial redundancy between ac-cesses to the memory location. The recent SSAPRE al-gorithm for eliminating partial redundancy using a sparse SSA representation forms the foundation for the present al-gorithm to eliminate redundancy among memory accesses, enabling us to achieve both computational and live range op-timality in our register promotion results. We discuss how to effect speculative code motion in the SSAPRE framework. We present two different algorithms for performing specu-lative code motion: the conservative speculation algorithm used in the absence of profile data, and the the profile-driven

A new algorithm, SSAPRE, for performing partial redundancy elimination based entirely on SSA form is presented. It achieves optimal code motion similar to lazy code motion [KRS94a, DS93], but is formulated independently and does not involve iterative data flow analysis and bit vectors in its solution. It not only exhibits the characteristics common to other sparse approaches, but also inherits the advantages shared by other SSA-based optimization techniques. SSAPRE also maintains its output in the same SSA form as its input. In describing the algorithm, we state theorems with proofs giving our claims about SSAPRE. We also give additional description about our practical implementation of SSAPRE, and analyze and compare its performance with a bit-vector-based implementation of PRE. We conclude with some discussion of the implications of this work.

The paper presents a technique called Global Instruction Distribution that globally fine-tunes the code produced for a superscalar processor. The fine-tuning is effected by distributing instructions from one block to other blocks according to the control flow graph of the program. The method does not involve instruction scheduling, but models resource usage to find the best insertion points in the target basic block. We present our implementation of GID in a production compiler, and show how the GID framework allows incorporation of additional functions targeting different optimizations. Performance measurements on the MIPS R8000 are presented to demonstrate the practicality and efficacy of this approach.