Annotation-based feature extraction from sets of SBML models

Background: Model repositories such as BioModels Database provide computational models of biological systems for the scientific community. These models contain rich semantic annotations that link model entities to concepts in well-established bio-ontologies such as Gene Ontology. Consequently, thematically similar models are likely to share similar annotations. Based on this assumption, we argue that semantic annotations are a suitable tool to characterize sets of models. These characteristics improve model classification, allow to identify additional features for model retrieval tasks, and enable the comparison of sets of models. Results: In this paper we discuss four methods for annotation-based feature extraction from model sets. We tested all methods on sets of models in SBML format which were composed from BioModels Database. To characterize each of these sets, we analyzed and extracted concepts from three frequently used ontologies, namely Gene Ontology, ChEBI and SBO. We find that three out of the methods are suitable to determine characteristic features for arbitrary sets of models: The selected features vary depending on the underlying model set, and they are also specific to the chosen model set. We show that the identified features map on concepts that are higher up in the hierarchy of the ontologies than the concepts used for model annotations. Our analysis also reveals that the information content of concepts in ontologies and their usage for model annotation do not correlate. Conclusions: Annotation-based feature extraction enables the comparison of model sets, as opposed to existing methods for model-to-keyword comparison, or model-to-model comparison

The CombineArchiveWeb application -A web based tool to handle files associated with modelling results

Abstract. Sharing in silico experiments is essential for the advance of research in computational biology. Consequently, the COMBINE archive was designed as a digital container format. It eases the management of files related to a modelling result, fosters collaboration, and ultimately enables the exchange of reproducible simulation studies. However, manual handling of COMBINE archives is tedious and error prone. We therefore developed the CombineArchiveWeb application to support scientists in promoting and publishing their research by means of creating, exploring, modifying, and sharing archives. All files are equipped with meta data and can be distributed over the Web through shareable workspaces

TRAPLINE: a standardized and automated pipeline for RNA sequencing data analysis, evaluation and annotation

Background: Technical advances in Next Generation Sequencing (NGS) provide a means to acquire deeper insights into cellular functions. The lack of standardized and automated methodologies poses a challenge for the analysis and interpretation of RNA sequencing data. We critically compare and evaluate state-of-the-art bioinformatics approaches and present a workflow that integrates the best performing data analysis, data evaluation and annotation methods in a Transparent, Reproducible and Automated PipeLINE (TRAPLINE) for RNA sequencing data processing (suitable for Illumina, SOLiD and Solexa). Results: Comparative transcriptomics analyses with TRAPLINE result in a set of differentially expressed genes, their corresponding protein-protein interactions, splice variants, promoter activity, predicted miRNA-target interactions and files for single nucleotide polymorphism (SNP) calling. The obtained results are combined into a single file for downstream analysis such as network construction. We demonstrate the value of the proposed pipeline by characterizing the transcriptome of our recently described stem cell derived antibiotic selected cardiac bodies ('aCaBs'). Conclusion: TRAPLINE supports NGS-based research by providing a workflow that requires no bioinformatics skills, decreases the processing time of the analysis and works in the cloud. The pipeline is implemented in the biomedical research platform Galaxy and is freely accessible via www.sbi.uni-rostock.de/RNAseqTRAPLINE or the specific Galaxy manual page (https://usegalaxy.org/u/mwolfien/p/trapline-manual)

The RNA workbench: Best practices for RNA and high-throughput sequencing bioinformatics in Galaxy

RNA-based regulation has become a major research topic in molecular biology. The analysis of epigenetic and expression data is therefore incomplete if RNA-based regulation is not taken into account. Thus, it is increasingly important but not yet standard to combine RNA-centric data and analysis tools with other types of experimental data such as RNA-seq or ChIP-seq. Here, we present the RNA workbench, a comprehensive set of analysis tools and consolidated workflows that enable the researcher to combine these two worlds. Based on the Galaxy framework the workbench guarantees simple access, easy extension, flexible adaption to personal and security needs, and sophisticated analyses that are independent of command-line knowledge. Currently, it includes more than 50 bioinformatics tools that are dedicated to different research areas of RNA biology including RNA structure analysis, RNA alignment, RNA annotation, RNA-protein interaction, ribosome profiling, RNA-seq analysis and RNA target prediction. The workbench is developed and maintained by experts in RNA bioinformatics and the Galaxy framework. Together with the growing community evolving around this workbench, we are committed to keep the workbench up-to-date for future standards and needs, providing researchers with a reliable and robust framework for RNA data analysis

Toward community standards and software for whole-cell modeling

Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate, comprehensive models of complex cells. Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in SBML. Results: Our analysis revealed several challenges to representing WC models using the current standards. Conclusion: We, therefore, propose several new WC modeling standards, software, and databases. Significance:We anticipate that these new standards and software will enable more comprehensive models

Community-Driven Data Analysis Training for Biology

The primary problem with the explosion of biomedical datasets is not the data, not computational resources, and not the required storage space, but the general lack of trained and skilled researchers to manipulate and analyze these data. Eliminating this problem requires development of comprehensive educational resources. Here we present a community-driven framework that enables modern, interactive teaching of data analytics in life sciences and facilitates the development of training materials. The key feature of our system is that it is not a static but a continuously improved collection of tutorials. By coupling tutorials with a web-based analysis framework, biomedical researchers can learn by performing computation themselves through a web browser without the need to install software or search for example datasets. Our ultimate goal is to expand the breadth of training materials to include fundamental statistical and data science topics and to precipitate a complete re-engineering of undergraduate and graduate curricula in life sciences. This project is accessible at https://training.galaxyproject.org. We developed an infrastructure that facilitates data analysis training in life sciences. It is an interactive learning platform tuned for current types of data and research problems. Importantly, it provides a means for community-wide content creation and maintenance and, finally, enables trainers and trainees to use the tutorials in a variety of situations, such as those where reliable Internet access is unavailable

Galaxy workflows for clinical applications

We demonstrate the potential of Next Generation Sequencing (NGS), especially RNA-Sequencing (RNA-Seq) for diagnostic purposes in the clinic. Using the workflow management platform Galaxy, we propose an RNA-Seq data analysis workflow, which helps to identify unexplained symptoms. Our <b>TR</b>ansparent and <b>A</b>utomated <b>P</b>ipe<b>LINE</b>, short <b>TRAPLINE</b>, was recently published (Wolfien <i>et al</i>. 2016). A comprehensive analysis of fastq datasets with TRAPLINE will result in a set of significantly differentially expressed genes (DEG). The DEGs will be combined with predictions and database knowledge to finally identify disease biomarkers that are based on gene fusion, splice variants or extracellular RNAs. We showcase the pipeline with the example of breast cancer for biomarker discovery. In addition we offer local TRAPLINE server instances as well as Docker images and enabling anonymized storage and exchange of patient derived datasets. While using such Docker images one can easily upscale or distribute the required computational resource

TRAPLINE

Next Generation Sequencing (NGS) enables researchers to acquire deeper insights into cellular functions. The lack of standardized and automated methodologies poses a challenge for the analysis and interpretation of RNA sequencing data. We present a freely available, state-of-the-art bioinformatics workflow that integrates the best performing data analyses and data evaluation methods (www.sbi.uni-rostock.de/RNAseqTRAPLINE)<br

gene_exp.csv

Differentially expressed genes between the tested patients #1 and #2 and the control group. Values are given in RPK