SUMMARY: The assessment of novel phylogenetic models and inference methods is routinely being conducted via experiments on simulated as well as empirical data. When generating synthetic data it is often unclear how to set simulation parameters for the models and generate trees that appropriately reflect empirical model parameter distributions and tree shapes. As a solution, we present and make available a new database called 'RAxML Grove' currently comprising more than 60 000 inferred trees and respective model parameter estimates from fully anonymized empirical datasets that were analyzed using RAxML and RAxML-NG on two web servers. We also describe and make available two simple applications of RAxML Grove to exemplify its usage and highlight its utility for designing realistic simulation studies and analyzing empirical model parameter and tree shape distributions. AVAILABILITY AND IMPLEMENTATION: RAxML Grove is freely available at https://github.com/angtft/RAxMLGrove. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Currently, more than 40 sequence tandem repeat detectors are published, providing heterogeneous, partly complementary, partly conflicting results. RESULTS: We present TRAL, a tandem repeat annotation library that allows running and parsing of various detection outputs, clustering of redundant or overlapping annotations, several statistical frameworks for filtering false positive annotations, and importantly a tandem repeat annotation and refinement module based on circular profile hidden Markov models (cpHMMs). Using TRAL, we evaluated the performance of a multi-step tandem repeat annotation workflow on 547 085 sequences in UniProtKB/Swiss-Prot. The researcher can use these results to predict run-times for specific datasets, and to choose annotation complexity accordingly. AVAILABILITY AND IMPLEMENTATION: TRAL is an open-source Python 3 library and is available, together with documentation and tutorials via http://www.vital-it.ch/software/tral. CONTACT: [email protected].

BACKGROUND: Available methods to simulate nucleotide or amino acid data typically use Markov models to simulate each position independently. These approaches are not appropriate to assess the performance of combinatorial and probabilistic methods that look for coevolving positions in nucleotide or amino acid sequences. RESULTS: We have developed a web-based platform that gives a user-friendly access to two phylogenetic-based methods implementing the Coev model: the evaluation of coevolving scores and the simulation of coevolving positions. We have also extended the capabilities of the Coev model to allow for the generalization of the alphabet used in the Markov model, which can now analyse both nucleotide and amino acid data sets. The simulation of coevolving positions is novel and builds upon the developments of the Coev model. It allows user to simulate pairs of dependent nucleotide or amino acid positions. CONCLUSIONS: The main focus of our paper is the new simulation method we present for coevolving positions. The implementation of this method is embedded within the web platform Coev-web that is freely accessible at http://coev.vital-it.ch/, and was tested in most modern web browsers.

MOTIVATION: The detection of positive selection is widely used to study gene and genome evolution, but its application remains limited by the high computational cost of existing implementations. We present a series of computational optimizations for more efficient estimation of the likelihood function on large-scale phylogenetic problems. We illustrate our approach using the branch-site model of codon evolution. RESULTS: We introduce novel optimization techniques that substantially outperform both CodeML from the PAML package and our previously optimized sequential version SlimCodeML. These techniques can also be applied to other likelihood-based phylogeny software. Our implementation scales well for large numbers of codons and/or species. It can therefore analyse substantially larger datasets than CodeML. We evaluated FastCodeML on different platforms and measured average sequential speedups of FastCodeML (single-threaded) versus CodeML of up to 5.8, average speedups of FastCodeML (multi-threaded) versus CodeML on a single node (shared memory) of up to 36.9 for 12 CPU cores, and average speedups of the distributed FastCodeML versus CodeML of up to 170.9 on eight nodes (96 CPU cores in total). AVAILABILITY AND IMPLEMENTATION: ftp://ftp.vital-it.ch/tools/FastCodeML/ CONTACT: [email protected] or [email protected].

In addition to multi-national Grid infrastructures, several countries operate their own national Grid infrastructures to support science and industry within national borders. These infrastructures have the benefit of better satisfying the needs of local, regional and national user communities. Although Switzerland has strong research groups in several fields of distributed computing, only recently a national Grid effort was kick-started to integrate a truly heterogeneous set of resource providers, middleware pools, and users. In the following article we discuss our efforts to start Grid activities at a national scale to combine several scientific communities and geographical domains. We make a strong case for the need of standards that have to be built on top of existing software systems in order to provide support for a heterogeneous Grid infrastructure.

Web services are fundamental building blocks for Service Oriented Architectures and Grid computing that are applied in many scientific domains such as bioinformatics. We have designed and implemented a multi-protocol and multifunctional Web service that supports today's most important industry standards. We show an actual implementation of a bioinformatics database application: HitKeeper, that is now enhanced by programmable Web services interfaces as well as HTML-form based Web access. In this way, a wide range of biologists and bioinformaticians are addressed. We also satisfy an important recent requirement in the e-science community.

Programmatic access to data and tools through the web using so-called web services has an important role to play in bioinformatics. In this article, we discuss the most popular approaches based on SOAP/WS-I and REST and describe our, a cross section of the community, experiences with providing and using web services in the context of biological sequence analysis. We briefly review main technological approaches as well as best practice hints that are useful for both users and developers. Finally, syntactic and semantic data integration issues with multiple web services are discussed.

Data replication is an important aspect in a data grid for increasing fault tolerance and availability. Many grid replication tools or middleware systems deal with read-only files which imply that replicated data items are always consistent. However, there are several applications that do require updates to existing data and the respective replicas. In this article, we present a replica consistency service that allows for replica updates in a single-master scenario with lazy update synchronisation. The system allows for updates of (heterogeneous) relational databases, and it is designed to support flat files as well. It keeps remote replicas synchronised and partially ("lazily") consistent. We report on the design and implementation of a novel "relaxed" replica consistency service and show its usefulness in a typical application use case.

The use of meta-schedulers for resource management in large-scale distributed systems often leads to a hierarchy of schedulers. In this paper, we discuss why existing meta-scheduling hierarchies are sometimes not sufficient for Grid systems due to their inability to re-organise jobs already scheduled locally. Such a job re-organisation is required to adapt to evolving loads which are common in heavily used Grid infrastructures. We propose a peer-topeer scheduling model and evaluate it using case studies and mathematical modelling. We detail the DIANA (Data Intensive and Network Aware) scheduling algorithm and its queue management system for coping with the load distribution and for supporting bulk job scheduling. We demonstrate that such a system is beneficial for dynamic, distributed and self-organizing resource management and can assist in optimizing load or job distribution in complex Grid infrastructures.

Modern biology has become a science of information, analysis and prediction, coalescing into computational biology -- a single discipline at the crossroads of life sciences, informatics, and mathematics. New developments in information and communications technology as well as high-performance computing enable researchers to address new demanding scientific problems which seemed far out of reach only a few years ago. The computational requirements of most applications in computational biology differ significantly from the requirements of other users of highthroughput computing such as high energy physics. To address these needs, the SwissBioGrid initiative, a collaboration among several partner institutions with a broad spectrum of expertise, was started over a year ago. In this paper, we report on its current status and achievements as well as the lessons learned which are of interest to the wider e-Science and Grid communities.

Bioinformatics algorithms such as sequence alignment methods based on profile-HMM (Hidden Markov Model) are popular but CPU-intensive. If large amounts of data are processed, a single computer often runs for many hours or even days. High performance infrastructures such as clusters or computational Grids provide the techniques to speed up the process by distributing the workload to remote nodes, running parts of the work load in parallel. Biologists often do not have access to such hardware systems. Therefore, we propose a new system using a modern Grid approach to optimise an embarrassingly parallel problem. We achieve speed ups by at least two orders of magnitude given that we can use a powerful, world-wide distributed Grid infrastructure. For large-scale problems our method can outperform algorithms designed for mid-size clusters even considering additional latencies imposed by Grid infrastructures.

Abstract The vision of Grid computing is to facilitate worldwide resource sharing among distributed collaborations. With the help of numerous national and international Grid projects, this vision is becoming reality and Grid systems are attracting an ever increasing user base. However, Grids are still quite complex software systems whose efficient use is a difficult and error‐prone task. In this paper we present performance engineering techniques that aim to facilitate an efficient use of Grid systems, in particular systems that deal with the management of large‐scale data sets in the tera‐ and petabyte range (also referred to as data Grids). These techniques are applicable at different layers of a Grid architecture and we discuss the tools required at each of these layers to implement them. Having discussed important performance engineering techniques, we investigate how major Grid projects deal with performance issues particularly related to data Grids and how they implement the techniques presented. Copyright © 2005 John Wiley & Sons, Ltd.

Grid technologies are more and more used in scientific as well as in industrial environments but often documentation and the correct usage are either not sufficient or not too well understood. Comprehensive training with hands-on experience helps people first to understand the technology and second to use it in a correct and efficient way. We have organised and run several training sessions in different locations all over the world and provide our experience. The major factors of success are a solid base of theoretical lectures and, more dominantly, a facility that allows for practical Grid exercises during and possibly after tutorial sessions.

In wide area computing systems, it is often desirable to create remote read-only copies (replicas) of files. Replication can be used to reduce access latency, improve data locality, and/or increase robustness, scalability and performance for distributed applications. We define a replica location service (RLS) as a system that maintains and provides access to information about the physical locations of copies. An RLS typically functions as one component of a data grid architecture. This paper makes the following contributions. First, we characterize RLS requirements. Next, we describe a parameterized architectural framework, which we name Giggle (for GIGa-scale Global Location Engine), within which a wide range of RLSs can be defined. We define several concrete instantiations of this framework with different performance characteristics. Finally, we present initial performance results for an RLS prototype, demonstrating that RLS systems can be constructed that meet performance goals.

Abstract The accelerated development in peer‐to‐peer and Grid computing has positioned them as promising next‐generation computing platforms. They enable the creation of virtual enterprises for sharing resources distributed across the world. However, resource management, application development and usage models in these environments is a complex undertaking. This is due to the geographic distribution of resources that are owned by different organizations or peers. The resource owners of each of these resources have different usage or access policies and cost models, and varying loads and availability. In order to address complex resource management issues, we have proposed a computational economy framework for resource allocation and for regulating supply and demand in Grid computing environments. This framework provides mechanisms for optimizing resource provider and consumer objective functions through trading and brokering services. In a real world market, there exist various economic models for setting the price of services based on supply‐and‐demand and their value to the user. They include commodity market, posted price, tender and auction models. In this paper, we discuss the use of these models for interaction between Grid components to decide resource service value, and the necessary infrastructure to realize each model. In addition to usual services offered by Grid computing systems, we need an infrastructure to support interaction protocols, allocation mechanisms, currency, secure banking and enforcement services. We briefly discuss existing technologies that provide some of these services and show their usage in developing the Nimrod‐G grid resource broker. Furthermore, we demonstrate the effectiveness of some of the economic models in resource trading and scheduling using the Nimrod/G resource broker, with deadline and cost constrained scheduling for two different optimization strategies, on the World‐Wide Grid testbed that has resources distributed across five continents. Copyright © 2002 John Wiley & Sons, Ltd.

Data Grids are currently proposed solutions to large scale data management problems including efficient file transfer and replication. Large amounts of data and the world-wide distribution of data stores contribute to the complexity of the data management challenge. Recent architecture proposals and prototypes deal with replication of read-only files but do not address the replica synchronisation problem. We propose a new Grid service, called Grid Consistency Service (GCS), that sits on top of existing Data Grid services and allows for replica update synchronisation and consistency maintenance. We give models for different levels of consistency provided to the Grid user and discuss how they can be included into a replica consistency service for a Data Grid. 1

Data replication is a key issue in a data grid and can be managed in different ways and at different levels of granularity: for example, at the file level or the object level. In the high-energy physics community, data grids are being developed to support the distributed analysis of experimental data. We have produced a prototype data replication tool, the Grid Data Management Pilot (GDMP) that is in production use in one physics experiment, with middleware provided by the Globus toolkit used for authentication, data movement and other purposes. We present a new, enhanced GDMP architecture and prototype implementation that uses Globus data-grid tools for efficient file replication. We also explain how this architecture can address object replication issues in an object-oriented database management system. File transfer over wide-area networks requires specific performance tuning in order to gain optimal data transfer rates. We present performance results obtained with GridFTP, an enhanced version of FTP, and discuss tuning parameters.