BioWorkbench: A High-Performance Framework for Managing and Analyzing Bioinformatics Experiments

Advances in sequencing techniques have led to exponential growth in biological data, demanding the development of large-scale bioinformatics experiments. Because these experiments are computation- and data-intensive, they require high-performance computing (HPC) techniques and can benefit from specialized technologies such as Scientific Workflow Management Systems (SWfMS) and databases. In this work, we present BioWorkbench, a framework for managing and analyzing bioinformatics experiments. This framework automatically collects provenance data, including both performance data from workflow execution and data from the scientific domain of the workflow application. Provenance data can be analyzed through a web application that abstracts a set of queries to the provenance database, simplifying access to provenance information. We evaluate BioWorkbench using three case studies: SwiftPhylo, a phylogenetic tree assembly workflow; SwiftGECKO, a comparative genomics workflow; and RASflow, a RASopathy analysis workflow. We analyze each workflow from both computational and scientific domain perspectives, by using queries to a provenance and annotation database. Some of these queries are available as a pre-built feature of the BioWorkbench web application. Through the provenance data, we show that the framework is scalable and achieves high-performance, reducing up to 98% of the case studies execution time. We also show how the application of machine learning techniques can enrich the analysis process

The benefits of in silico modeling to identify possible small-molecule drugs and their off-target interactions

Accepted for publication in a future issue of Future Medicinal Chemistry.The research into the use of small molecules as drugs continues to be a key driver in the development of molecular databases, computer-aided drug design software and collaborative platforms. The evolution of computational approaches is driven by the essential criteria that a drug molecule has to fulfill, from the affinity to targets to minimal side effects while having adequate absorption, distribution, metabolism, and excretion (ADME) properties. A combination of ligand- and structure-based drug development approaches is already used to obtain consensus predictions of small molecule activities and their off-target interactions. Further integration of these methods into easy-to-use workflows informed by systems biology could realize the full potential of available data in the drug discovery and reduce the attrition of drug candidates.Peer reviewe

Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows

We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows. Finally, we discuss several major problems, including the occurrence of drug-resistant mutations, drug promiscuity, and the design of dual-effect inhibitors.Fil: Goncearenco, Alexander. National Institutes of Health; Estados UnidosFil: Li, Minghui. Soochow University; China. National Institutes of Health; Estados UnidosFil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Shoemaker, Benjamin A. National Institutes of Health; Estados UnidosFil: Panchenko, Anna R. National Institutes of Health; Estados Unido

Agent-based modeling: a systematic assessment of use cases and requirements for enhancing pharmaceutical research and development productivity.

A crisis continues to brew within the pharmaceutical research and development (R&D) enterprise: productivity continues declining as costs rise, despite ongoing, often dramatic scientific and technical advances. To reverse this trend, we offer various suggestions for both the expansion and broader adoption of modeling and simulation (M&S) methods. We suggest strategies and scenarios intended to enable new M&S use cases that directly engage R&D knowledge generation and build actionable mechanistic insight, thereby opening the door to enhanced productivity. What M&S requirements must be satisfied to access and open the door, and begin reversing the productivity decline? Can current methods and tools fulfill the requirements, or are new methods necessary? We draw on the relevant, recent literature to provide and explore answers. In so doing, we identify essential, key roles for agent-based and other methods. We assemble a list of requirements necessary for M&S to meet the diverse needs distilled from a collection of research, review, and opinion articles. We argue that to realize its full potential, M&S should be actualized within a larger information technology framework--a dynamic knowledge repository--wherein models of various types execute, evolve, and increase in accuracy over time. We offer some details of the issues that must be addressed for such a repository to accrue the capabilities needed to reverse the productivity decline

Innovative in silico approaches to address avian flu using grid technology

The recent years have seen the emergence of diseases which have spread very quickly all around the world either through human travels like SARS or animal migration like avian flu. Among the biggest challenges raised by infectious emerging diseases, one is related to the constant mutation of the viruses which turns them into continuously moving targets for drug and vaccine discovery. Another challenge is related to the early detection and surveillance of the diseases as new cases can appear just anywhere due to the globalization of exchanges and the circulation of people and animals around the earth, as recently demonstrated by the avian flu epidemics. For 3 years now, a collaboration of teams in Europe and Asia has been exploring some innovative in silico approaches to better tackle avian flu taking advantage of the very large computing resources available on international grid infrastructures. Grids were used to study the impact of mutations on the effectiveness of existing drugs against H5N1 and to find potentially new leads active on mutated strains. Grids allow also the integration of distributed data in a completely secured way. The paper presents how we are currently exploring how to integrate the existing data sources towards a global surveillance network for molecular epidemiology.Comment: 7 pages, submitted to Infectious Disorders - Drug Target

XML in Motion from Genome to Drug

Information technology (IT) has emerged as a central to the solution of contemporary genomics and drug discovery problems. Researchers involved in genomics, proteomics, transcriptional profiling, high throughput structure determination, and in other sub-disciplines of bioinformatics have direct impact on this IT revolution. As the full genome sequences of many species, data from structural genomics, micro-arrays, and proteomics became available, integration of these data to a common platform require sophisticated bioinformatics tools. Organizing these data into knowledgeable databases and developing appropriate software tools for analyzing the same are going to be major challenges. XML (eXtensible Markup Language) forms the backbone of biological data representation and exchange over the internet, enabling researchers to aggregate data from various heterogeneous data resources. The present article covers a comprehensive idea of the integration of XML on particular type of biological databases mainly dealing with sequence-structure-function relationship and its application towards drug discovery. This e-medical science approach should be applied to other scientific domains and the latest trend in semantic web applications is also highlighted

CaGrid Workflow Toolkit: A taverna based workflow tool for cancer grid

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SGABU computational platform for multiscale modeling:Bridging the gap between education and research

BACKGROUND AND OBJECTIVE: In accordance with the latest aspirations in the field of bioengineering, there is a need to create a web accessible, but powerful cloud computational platform that combines datasets and multiscale models related to bone modeling, cancer, cardiovascular diseases and tissue engineering. The SGABU platform may become a powerful information system for research and education that can integrate data, extract information, and facilitate knowledge exchange with the goal of creating and developing appropriate computing pipelines to provide accurate and comprehensive biological information from the molecular to organ level. METHODS: The datasets integrated into the platform are obtained from experimental and/or clinical studies and are mainly in tabular or image file format, including metadata. The implementation of multiscale models, is an ambitious effort of the platform to capture phenomena at different length scales, described using partial and ordinary differential equations, which are solved numerically on complex geometries with the use of the finite element method. The majority of the SGABU platform's simulation pipelines are provided as Common Workflow Language (CWL) workflows. Each of them requires creating a CWL implementation on the backend and a user-friendly interface using standard web technologies. Platform is available at https://sgabu-test.unic.kg.ac.rs/login. RESULTS: The main dashboard of the SGABU platform is divided into sections for each field of research, each one of which includes a subsection of datasets and multiscale models. The datasets can be presented in a simple form as tabular data, or using technologies such as Plotly.js for 2D plot interactivity, Kitware Paraview Glance for 3D view. Regarding the models, the usage of Docker containerization for packing the individual tools and CWL orchestration for describing inputs with validation forms and outputs with tabular views for output visualization, interactive diagrams, 3D views and animations. CONCLUSIONS: In practice, the structure of SGABU platform means that any of the integrated workflows can work equally well on any other bioengineering platform. The key advantage of the SGABU platform over similar efforts is its versatility offered with the use of modern, modular, and extensible technology for various levels of architecture.</p

Toward a Standardized Strategy of Clinical Metabolomics for the Advancement of Precision Medicine

Despite the tremendous success, pitfalls have been observed in every step of a clinical metabolomics workflow, which impedes the internal validity of the study. Furthermore, the demand for logistics, instrumentations, and computational resources for metabolic phenotyping studies has far exceeded our expectations. In this conceptual review, we will cover inclusive barriers of a metabolomics-based clinical study and suggest potential solutions in the hope of enhancing study robustness, usability, and transferability. The importance of quality assurance and quality control procedures is discussed, followed by a practical rule containing five phases, including two additional "pre-pre-" and "post-post-" analytical steps. Besides, we will elucidate the potential involvement of machine learning and demonstrate that the need for automated data mining algorithms to improve the quality of future research is undeniable. Consequently, we propose a comprehensive metabolomics framework, along with an appropriate checklist refined from current guidelines and our previously published assessment, in the attempt to accurately translate achievements in metabolomics into clinical and epidemiological research. Furthermore, the integration of multifaceted multi-omics approaches with metabolomics as the pillar member is in urgent need. When combining with other social or nutritional factors, we can gather complete omics profiles for a particular disease. Our discussion reflects the current obstacles and potential solutions toward the progressing trend of utilizing metabolomics in clinical research to create the next-generation healthcare system.11Ysciescopu