Journal of Integrative Bioinformatics最新文献

EvoPPI (http://evoppi.i3s.up.pt), a meta-database for protein-protein interactions (PPI), has been upgraded (EvoPPI3) to accept new types of data, namely, PPI from patients, cell lines, and animal models, as well as data from gene modifier experiments, for nine neurodegenerative polyglutamine (polyQ) diseases caused by an abnormal expansion of the polyQ tract. The integration of the different types of data allows users to easily compare them, as here shown for Ataxin-1, the polyQ protein involved in spinocerebellar ataxia type 1 (SCA1) disease. Using all available datasets and the data here obtained for Drosophila melanogaster wt and exp Ataxin-1 mutants (also available at EvoPPI3), we show that, in humans, the Ataxin-1 network is much larger than previously thought (380 interactors), with at least 909 interactors. The functional profiling of the newly identified interactors is similar to the ones already reported in the main PPI databases. 16 out of 909 interactors are putative novel SCA1 therapeutic targets, and all but one are already being studied in the context of this disease. The 16 proteins are mainly involved in binding and catalytic activity (mainly kinase activity), functional features already thought to be important in the SCA1 disease.

Science has become a highly competitive undertaking concerning, for example, resources, positions, students, and publications. At the same time, the number of journals presenting scientific findings skyrockets while the knowledge increase per manuscript seems to be diminishing. Science has also become ever more dependent on computational analyses. For example, virtually all biomedical applications involve computational data analysis. The science community develops many computational tools, and there are numerous alternatives for many computational tasks. The same is true for workflow management systems, leading to a tremendous duplication of efforts. Software quality is often of low concern, and typically, a small dataset is used as a proof of principle to support rapid publication. Installation and usage of such tools are complicated, so virtual machine images, containers, and package managers are employed more frequently. These simplify installation and ease of use but do not solve the software quality issue and duplication of effort. We believe that a community-wide collaboration is needed to (a) ensure software quality, (b) increase reuse of code, (c) force proper software review, (c) increase testing, and (d) make interoperability more seamless. Such a science software ecosystem will overcome current issues and increase trust in current data analyses.

Diagnosing diabetes early is critical as it helps patients live with the disease in a healthy way - through healthy eating, taking appropriate medical doses, and making patients more vigilant in their movements/activities to avoid wounds that are difficult to heal for diabetic patients. Data mining techniques are typically used to detect diabetes with high confidence to avoid misdiagnoses with other chronic diseases whose symptoms are similar to diabetes. Hidden Naïve Bayes is one of the algorithms for classification, which works under a data-mining model based on the assumption of conditional independence of the traditional Naïve Bayes. The results from this research study, which was conducted on the Pima Indian Diabetes (PID) dataset collection, show that the prediction accuracy of the HNB classifier achieved 82%. As a result, the discretization method increases the performance and accuracy of the HNB classifier.

Systems biology researchers need feasible solutions for editing and visualisation of large biological diagrams. Here, we present the ySBGN bidirectional converter that translates metabolic pathways, developed in the general-purpose yEd Graph Editor (using the GraphML format) into the Systems Biology Graphical Notation Markup Language (SBGN-ML) standard format and vice versa. We illustrate the functionality of this converter by applying it to the translation of the ReconMap resource (available in the SBGN-ML format) to the yEd-specific GraphML and back. The ySBGN tool makes possible to draw extensive metabolic diagrams in a powerful general-purpose graph editor while providing results in the standard SBGN format.

Biomolecular networks, including genome-scale metabolic models (GSMMs), assemble the knowledge regarding the biological processes that happen inside specific organisms in a way that allows for analysis, simulation, and exploration. With the increasing availability of genome annotations and the development of powerful reconstruction tools, biomolecular networks continue to grow ever larger. While visual exploration can facilitate the understanding of such networks, the network sizes represent a major challenge for current visualisation systems. Building on promising results from the area of immersive analytics, which among others deals with the potential of immersive visualisation for data analysis, we present a concept for a hybrid user interface that combines a classical desktop environment with a virtual reality environment for the visual exploration of large biomolecular networks and corresponding data. We present system requirements and design considerations, describe a resulting concept, an envisioned technical realisation, and a systems biology usage scenario. Finally, we discuss remaining challenges.

This paper describes the design philosophy for our cloud-based virtual reality (VR) co-creation environment (CCE) for molecular modeling. Using interactive VR simulation can provide enhanced perspectives in molecular modeling for intuitive live demonstration and experimentation in the CCE. Then the use of the CCE can enhance knowledge creation by bringing people together to share and create ideas or knowledge that may not emerge otherwise. Our prototype CCE discussed here, which was developed to demonstrate our design philosophy, has already enabled multiple members to log in and touch virtual molecules running on a cloud server with no noticeable network latency via real-time artificial intelligence techniques. The CCE plays an essential role in the rational design of molecular robot parts, which consist of bio-molecules such as DNA and protein molecules.

Parkinson's disease is considered the second most frequent neurodegenerative disease. It is described by the loss of dopaminergic neurons in the mid-brain. For many decades, L-DOPA has been considered as the gold standard for treating Parkinson's disease motor symptoms, however, due to the decrease of efficacy, in the long run, there is an urgent need for novel antiparkinsonian drugs. Caffeine derivatives have been reported several times for their neuroprotective properties and dual blockade of monoamine oxidase (MAO) and adenosine A_2A receptors (AA_2AR). Natural products are currently attracting more focus due to structural diversity and safety in contrast to synthetic drugs. In the present work, computational studies were conducted on natural product-like caffeine derivatives to search for novel potent candidates acting as dual MAO-B inhibitors/AA_2AR antagonists for Parkinson's disease. Our findings revealed two natural products among the top hits: CNP0202316 and CNP0365210 fulfill the requirements of drugs acting on the brain. The selected lead compounds were further studied using molecular dynamics simulation to assess their stability with MAO-B. Current findings might shift the interest towards natural-based compounds and could be exploited to further optimize caffeine derivatives into a successful dual-target-directed drug for managing and halting the neuronal damage in Parkinson's disease patients.

Core facilities have to offer technologies that best serve the needs of their users and provide them a competitive advantage in research. They have to set up and maintain instruments in the range of ten to a hundred, which produce large amounts of data and serve thousands of active projects and customers. Particular emphasis has to be given to the reproducibility of the results. More and more, the entire process from building the research hypothesis, conducting the experiments, doing the measurements, through the data explorations and analysis is solely driven by very few experts in various scientific fields. Still, the ability to perform the entire data exploration in real-time on a personal computer is often hampered by the heterogeneity of software, the data structure formats of the output, and the enormous data sizes. These impact the design and architecture of the implemented software stack. At the Functional Genomics Center Zurich (FGCZ), a joint state-of-the-art research and training facility of ETH Zurich and the University of Zurich, we have developed the B-Fabric system, which has served for more than a decade, an entire life sciences community with fundamental data science support. In this paper, we sketch how such a system can be used to glue together data (including metadata), computing infrastructures (clusters and clouds), and visualization software to support instant data exploration and visual analysis. We illustrate our in-daily life implemented approach using visualization applications of mass spectrometry data.

The implementation of Artificial Intelligence (AI) still faces significant hurdles and one key factor is the access to data. One approach that could support that is federated machine learning (FL) since it allows for privacy preserving data access. For this proof of concept, a prediction model for coronary artery calcification scores (CACS) has been applied. The FL was trained based on the data in the different institutions, while the centralized machine learning model was trained on one allocation of data. Both algorithms predict patients with risk scores ≥5 based on age, biological sex, waist circumference, dyslipidemia and HbA1c. The centralized model yields a sensitivity of c. 66% and a specificity of c. 70%. The FL slightly outperforms that with a sensitivity of 67% while slightly underperforming it with a specificity of 69%. It could be demonstrated that CACS prediction is feasible via both, a centralized and an FL approach, and that both show very comparable accuracy. In order to increase accuracy, additional and a higher volume of patient data is required and for that FL is utterly necessary. The developed "CACulator" serves as proof of concept, is available as research tool and shall support future research to facilitate AI implementation.

Over the last years it has been observed that the progress in data collection in life science has created increasing demand and opportunities for advanced bioinformatics. This includes data management as well as the individual data analysis and often covers the entire data life cycle. A variety of tools have been developed to store, share, or reuse the data produced in the different domains such as genotyping. Especially imputation, as a subfield of genotyping, requires good Research Data Management (RDM) strategies to enable use and re-use of genotypic data. To aim for sustainable software, it is necessary to develop tools and surrounding ecosystems, which are reusable and maintainable. Reusability in the context of streamlined tools can e.g. be achieved by standardizing the input and output of the different tools and adapting to open and broadly used file formats. By using such established file formats, the tools can also be connected with others, improving the overall interoperability of the software. Finally, it is important to build strong communities that maintain the tools by developing and contributing new features and maintenance updates. In this article, concepts for this will be presented for an imputation service.