Implementing FAIR data management within the German Network for Bioinformatics Infrastructure (de.NBI) exemplified by selected use cases.

This article describes some use case studies and self-assessments of FAIR status of de.NBI services to illustrate the challenges and requirements for the definition of the needs of adhering to the FAIR (findable, accessible, interoperable and reusable) data principles in a large distributed bioinformatics infrastructure. We address the challenge of heterogeneity of wet lab technologies, data, metadata, software, computational workflows and the levels of implementation and monitoring of FAIR principles within the different bioinformatics sub-disciplines joint in de.NBI. On the one hand, this broad service landscape and the excellent network of experts are a strong basis for the development of useful research data management plans. On the other hand, the large number of tools and techniques maintained by distributed teams renders FAIR compliance challenging.

A German online survey of people who have experienced sleep paralysis.

We present some key findings from an online survey on isolated sleep paralysis. The aim of our study was to get a differentiated picture of the correlation between the frequency of sleep paralysis and several phenomena (symptoms, experiences) as well as factors correlated with these phenomena. We also investigated the role of gender in relation to the experience of sleep paralysis. We used a selected sample of subjects who had had at least one sleep paralysis experience, with a total of 380 subjects. On average, the participants experienced 10-20 sleep paralysis episodes. We found high and expected positive correlations between the frequency of sleep paralysis experiences and the amount of phenomena, emotions, and perceived shapes and forms experienced during sleep paralysis. An increased frequency of sleep paralysis also appears to lead to habituation and de-dramatization in some affected individuals. Interestingly, significant correlations are missing where one would have suspected them based on the previous hypotheses. Neither self-perceived general stress nor poor sleep hygiene appeared to influence the frequency of sleep paralysis. We found highly significant gender differences in some items. Women reported more experienced phenomena and emotions overall, had more frequent sleep paralysis experiences of the intruder and incubus type, and were significantly more likely to perceive concrete forms such as human figures or people they know. They were also more likely than men to report experiencing fearful emotions, especially the fear of going crazy. Most of these findings were based on exploratory questions; they require replication for validation.

A generally applicable lightweight method for calculating a value structure for tools and services in bioinformatics infrastructure projects.

Sustainable noncommercial bioinformatics infrastructures are a prerequisite to use and take advantage of the potential of big data analysis for research and economy. Consequently, funders, universities and institutes as well as users ask for a transparent value model for the tools and services offered. In this article, a generally applicable lightweight method is described by which bioinformatics infrastructure projects can estimate the value of tools and services offered without determining exactly the total costs of ownership. Five representative scenarios for value estimation from a rough estimation to a detailed breakdown of costs are presented. To account for the diversity in bioinformatics applications and services, the notion of service-specific 'service provision units' is introduced together with the factors influencing them and the main underlying assumptions for these 'value influencing factors'. Special attention is given on how to handle personnel costs and indirect costs such as electricity. Four examples are presented for the calculation of the value of tools and services provided by the German Network for Bioinformatics Infrastructure (de.NBI): one for tool usage, one for (Web-based) database analyses, one for consulting services and one for bioinformatics training events. Finally, from the discussed values, the costs of direct funding and the costs of payment of services by funded projects are calculated and compared.

The PRIDE database and related tools and resources in 2019: improving support for quantification data.

The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world's largest data repository of mass spectrometry-based proteomics data, and is one of the founding members of the global ProteomeXchange (PX) consortium. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published in Nucleic Acids Research in 2016. In the last 3 years, public data sharing through PRIDE (as part of PX) has definitely become the norm in the field. In parallel, data re-use of public proteomics data has increased enormously, with multiple applications. We first describe the new architecture of PRIDE Archive, the archival component of PRIDE. PRIDE Archive and the related data submission framework have been further developed to support the increase in submitted data volumes and additional data types. A new scalable and fault tolerant storage backend, Application Programming Interface and web interface have been implemented, as a part of an ongoing process. Additionally, we emphasize the improved support for quantitative proteomics data through the mzTab format. At last, we outline key statistics on the current data contents and volume of downloads, and how PRIDE data are starting to be disseminated to added-value resources including Ensembl, UniProt and Expression Atlas.

Proteomics Standards Initiative Extended FASTA Format.

Mass-spectrometry-based proteomics enables the high-throughput identification and quantification of proteins, including sequence variants and post-translational modifications (PTMs) in biological samples. However, most workflows require that such variations be included in the search space used to analyze the data, and doing so remains challenging with most analysis tools. In order to facilitate the search for known sequence variants and PTMs, the Proteomics Standards Initiative (PSI) has designed and implemented the PSI extended FASTA format (PEFF). PEFF is based on the very popular FASTA format but adds a uniform mechanism for encoding substantially more metadata about the sequence collection as well as individual entries, including support for encoding known sequence variants, PTMs, and proteoforms. The format is very nearly backward compatible, and as such, existing FASTA parsers will require little or no changes to be able to read PEFF files as FASTA files, although without supporting any of the extra capabilities of PEFF. PEFF is defined by a full specification document, controlled vocabulary terms, a set of example files, software libraries, and a file validator. Popular software and resources are starting to support PEFF, including the sequence search engine Comet and the knowledge bases neXtProt and UniProtKB. Widespread implementation of PEFF is expected to further enable proteogenomics and top-down proteomics applications by providing a standardized mechanism for encoding protein sequences and their known variations. All the related documentation, including the detailed file format specification and example files, are available at http://www.psidev.info/peff .

mzTab-M: A Data Standard for Sharing Quantitative Results in Mass Spectrometry Metabolomics.

Mass spectrometry (MS) is one of the primary techniques used for large-scale analysis of small molecules in metabolomics studies. To date, there has been little data format standardization in this field, as different software packages export results in different formats represented in XML or plain text, making data sharing, database deposition, and reanalysis highly challenging. Working within the consortia of the Metabolomics Standards Initiative, Proteomics Standards Initiative, and the Metabolomics Society, we have created mzTab-M to act as a common output format from analytical approaches using MS on small molecules. The format has been developed over several years, with input from a wide range of stakeholders. mzTab-M is a simple tab-separated text format, but importantly, the structure is highly standardized through the design of a detailed specification document, tightly coupled to validation software, and a mandatory controlled vocabulary of terms to populate it. The format is able to represent final quantification values from analyses, as well as the evidence trail in terms of features measured directly from MS (e.g., LC-MS, GC-MS, DIMS, etc.) and different types of approaches used to identify molecules. mzTab-M allows for ambiguity in the identification of molecules to be communicated clearly to readers of the files (both people and software). There are several implementations of the format available, and we anticipate widespread adoption in the field.

The mzIdentML Data Standard Version 1.2, Supporting Advances in Proteome Informatics.

The first stable version of the Proteomics Standards Initiative mzIdentML open data standard (version 1.1) was published in 2012-capturing the outputs of peptide and protein identification software. In the intervening years, the standard has become well-supported in both commercial and open software, as well as a submission and download format for public repositories. Here we report a new release of mzIdentML (version 1.2) that is required to keep pace with emerging practice in proteome informatics. New features have been added to support: (1) scores associated with localization of modifications on peptides; (2) statistics performed at the level of peptides; (3) identification of cross-linked peptides; and (4) support for proteogenomics approaches. In addition, there is now improved support for the encoding of de novo sequencing of peptides, spectral library searches, and protein inference. As a key point, the underlying XML schema has only undergone very minor modifications to simplify as much as possible the transition from version 1.1 to version 1.2 for implementers, but there have been several notable updates to the format specification, implementation guidelines, controlled vocabularies and validation software. mzIdentML 1.2 can be described as backwards compatible, in that reading software designed for mzIdentML 1.1 should function in most cases without adaptation. We anticipate that these developments will provide a continued stable base for software teams working to implement the standard. All the related documentation is accessible at http://www.psidev.info/mzidentml.

2016 update of the PRIDE database and its related tools.

The PRoteomics IDEntifications (PRIDE) database is one of the world-leading data repositories of mass spectrometry (MS)-based proteomics data. Since the beginning of 2014, PRIDE Archive (http://www.ebi.ac.uk/pride/archive/) is the new PRIDE archival system, replacing the original PRIDE database. Here we summarize the developments in PRIDE resources and related tools since the previous update manuscript in the Database Issue in 2013. PRIDE Archive constitutes a complete redevelopment of the original PRIDE, comprising a new storage backend, data submission system and web interface, among other components. PRIDE Archive supports the most-widely used PSI (Proteomics Standards Initiative) data standard formats (mzML and mzIdentML) and implements the data requirements and guidelines of the ProteomeXchange Consortium. The wide adoption of ProteomeXchange within the community has triggered an unprecedented increase in the number of submitted data sets (around 150 data sets per month). We outline some statistics on the current PRIDE Archive data contents. We also report on the status of the PRIDE related stand-alone tools: PRIDE Inspector, PRIDE Converter 2 and the ProteomeXchange submission tool. Finally, we will give a brief update on the resources under development 'PRIDE Cluster' and 'PRIDE Proteomes', which provide a complementary view and quality-scored information of the peptide and protein identification data available in PRIDE Archive.

Proteomics Standards Initiative: Fifteen Years of Progress and Future Work.

The Proteomics Standards Initiative (PSI) of the Human Proteome Organization (HUPO) has now been developing and promoting open community standards and software tools in the field of proteomics for 15 years. Under the guidance of the chair, cochairs, and other leadership positions, the PSI working groups are tasked with the development and maintenance of community standards via special workshops and ongoing work. Among the existing ratified standards, the PSI working groups continue to update PSI-MI XML, MITAB, mzML, mzIdentML, mzQuantML, mzTab, and the MIAPE (Minimum Information About a Proteomics Experiment) guidelines with the advance of new technologies and techniques. Furthermore, new standards are currently either in the final stages of completion (proBed and proBAM for proteogenomics results as well as PEFF) or in early stages of design (a spectral library standard format, a universal spectrum identifier, the qcML quality control format, and the Protein Expression Interface (PROXI) web services Application Programming Interface). In this work we review the current status of all of these aspects of the PSI, describe synergies with other efforts such as the ProteomeXchange Consortium, the Human Proteome Project, and the metabolomics community, and provide a look at future directions of the PSI.

Boolean modeling techniques for protein co-expression networks in systems medicine.

INTRODUCTION: Application of systems biology/systems medicine approaches is promising for proteomics/biomedical research, but requires selection of an adequate modeling type. AREAS COVERED: This article reviews the existing Boolean network modeling approaches, which provide in comparison with alternative modeling techniques several advantages for the processing of proteomics data. Application of methods for inference, reduction and validation of protein co-expression networks that are derived from quantitative high-throughput proteomics measurements is presented. It's also shown how Boolean models can be used to derive system-theoretic characteristics that describe both the dynamical behavior of such networks as a whole and the properties of different cell states (e.g. healthy or diseased cell states). Furthermore, application of methods derived from control theory is proposed in order to simulate the effects of therapeutic interventions on such networks, which is a promising approach for the computer-assisted discovery of biomarkers and drug targets. Finally, the clinical application of Boolean modeling analyses is discussed. Expert commentary: Boolean modeling of proteomics data is still in its infancy. Progress in this field strongly depends on provision of a repository with public access to relevant reference models. Also required are community supported standards that facilitate input of both proteomics and patient related data (e.g. age, gender, laboratory results, etc.).

Controlled vocabularies and ontologies in proteomics: overview, principles and practice.

This paper focuses on the use of controlled vocabularies (CVs) and ontologies especially in the area of proteomics, primarily related to the work of the Proteomics Standards Initiative (PSI). It describes the relevant proteomics standard formats and the ontologies used within them. Software and tools for working with these ontology files are also discussed. The article also examines the "mapping files" used to ensure correct controlled vocabulary terms that are placed within PSI standards and the fulfillment of the MIAPE (Minimum Information about a Proteomics Experiment) requirements. This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. Guest Editors: Martin Eisenacher and Christian Stephan.

The mzQuantML data standard for mass spectrometry-based quantitative studies in proteomics.

The range of heterogeneous approaches available for quantifying protein abundance via mass spectrometry (MS)(1) leads to considerable challenges in modeling, archiving, exchanging, or submitting experimental data sets as supplemental material to journals. To date, there has been no widely accepted format for capturing the evidence trail of how quantitative analysis has been performed by software, for transferring data between software packages, or for submitting to public databases. In the context of the Proteomics Standards Initiative, we have developed the mzQuantML data standard. The standard can represent quantitative data about regions in two-dimensional retention time versus mass/charge space (called features), peptides, and proteins and protein groups (where there is ambiguity regarding peptide-to-protein inference), and it offers limited support for small molecule (metabolomic) data. The format has structures for representing replicate MS runs, grouping of replicates (for example, as study variables), and capturing the parameters used by software packages to arrive at these values. The format has the capability to reference other standards such as mzML and mzIdentML, and thus the evidence trail for the MS workflow as a whole can now be described. Several software implementations are available, and we encourage other bioinformatics groups to use mzQuantML as an input, internal, or output format for quantitative software and for structuring local repositories. All project resources are available in the public domain from the HUPO Proteomics Standards Initiative http://www.psidev.info/mzquantml.

The mzIdentML data standard for mass spectrometry-based proteomics results.

We report the release of mzIdentML, an exchange standard for peptide and protein identification data, designed by the Proteomics Standards Initiative. The format was developed by the Proteomics Standards Initiative in collaboration with instrument and software vendors, and the developers of the major open-source projects in proteomics. Software implementations have been developed to enable conversion from most popular proprietary and open-source formats, and mzIdentML will soon be supported by the major public repositories. These developments enable proteomics scientists to start working with the standard for exchanging and publishing data sets in support of publications and they provide a stable platform for bioinformatics groups and commercial software vendors to work with a single file format for identification data.

Prospective study validating a multidimensional treatment decision score predicting the 24-month outcome in untreated patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis, the ProVal-MS study.

INTRODUCTION: In Multiple Sclerosis (MS), patients´ characteristics and (bio)markers that reliably predict the individual disease prognosis at disease onset are lacking. Cohort studies allow a close follow-up of MS histories and a thorough phenotyping of patients. Therefore, a multicenter cohort study was initiated to implement a wide spectrum of data and (bio)markers in newly diagnosed patients. METHODS: ProVal-MS (Prospective study to validate a multidimensional decision score that predicts treatment outcome at 24 months in untreated patients with clinically isolated syndrome or early Relapsing-Remitting-MS) is a prospective cohort study in patients with clinically isolated syndrome (CIS) or Relapsing-Remitting (RR)-MS (McDonald 2017 criteria), diagnosed within the last two years, conducted at five academic centers in Southern Germany. The collection of clinical, laboratory, imaging, and paraclinical data as well as biosamples is harmonized across centers. The primary goal is to validate (discrimination and calibration) the previously published DIFUTURE MS-Treatment Decision score (MS-TDS). The score supports clinical decision-making regarding the options of early (within 6 months after study baseline) platform medication (Interferon beta, glatiramer acetate, dimethyl/diroximel fumarate, teriflunomide), or no immediate treatment (> 6 months after baseline) of patients with early RR-MS and CIS by predicting the probability of new or enlarging lesions in cerebral magnetic resonance images (MRIs) between 6 and 24 months. Further objectives are refining the MS-TDS score and providing data to identify new markers reflecting disease course and severity. The project also provides a technical evaluation of the ProVal-MS cohort within the IT-infrastructure of the DIFUTURE consortium (Data Integration for Future Medicine) and assesses the efficacy of the data sharing techniques developed. PERSPECTIVE: Clinical cohorts provide the infrastructure to discover and to validate relevant disease-specific findings. A successful validation of the MS-TDS will add a new clinical decision tool to the armamentarium of practicing MS neurologists from which newly diagnosed MS patients may take advantage. Trial registration ProVal-MS has been registered in the German Clinical Trials Register, `Deutsches Register Klinischer Studien` (DRKS)-ID: DRKS00014034, date of registration: 21 December 2018; https://drks.de/search/en/trial/DRKS00014034.

Prospective randomized comparison of short-access mother-baby cholangioscopy versus direct cholangioscopy with ultraslim gastroscopes.

BACKGROUND: Mother-baby technologies, the criterion standard for cholangioscopy, have several limitations. A novel, short-access, mother-baby (SAMBA) system may improve this technique. Direct cholangioscopy (DC) was recently developed as an alternative to mother-baby cholangioscopy. OBJECTIVE: Comparison of success rates with SAMBA and DC. DESIGN: Single-center, randomized, controlled trial. SETTING: Academic tertiary-care referral center. PATIENTS: Sixty patients with suspected cholangiopathies randomized to either SAMBA (n = 30) or DC (n = 30). INTERVENTION: Cholangioscopy under deep sedation. MAIN OUTCOME MEASUREMENTS: Technical success rate of diagnostic or therapeutic procedure. RESULTS: A total of 24 and 21 diagnostic procedures were performed in the SAMBA and DC groups, respectively. There were no significant differences in the overall technical success rates between SAMBA (90.0%) and DC (86.7%) (P = 1.0). There was better correlation between the endoscopic prediction and histologic findings in DC (P = .013). Procedure times were shorter in DC (P < .03). In patients without significant stenoses, SAMBA allowed intrahepatic bile duct exploration in all cases, compared with 10.5% of cases in DC (P < .01). No differences regarding adverse event rates between the groups occurred (10.0% both groups). LIMITATIONS: Small sample size. Heterogeneous indications for cholangioscopy. DC requires advanced skills of the endoscopist. The study is not replicable. CONCLUSION: SAMBA and DC offer high technical success rates for diagnostic and therapeutic interventions. The advantages of DC consist of superior imaging, shorter total procedure time, and a wider working channel for adequate tissue sampling. SAMBA is better than DC with regard to intraductal stability and accessibility of the intrahepatic bile ducts.

[Chair of Mining Engineering and Mineral Economics-the Future]. / Bergbaukunde, quo vadis?

In order to tackle climate change and increasing competition in access to resources, the European Union has defined far-reaching transformations in the areas of energy and digitalisation as well as the conversion of the economic system towards an inclusive, circular economy in the so-called Green Deal. From a mining perspective, these transformations mean a continued growing demand for raw materials, which must be met by extracting mineral raw materials from primary deposits. However, increased quantities with "business as usual" would also increase the environmental and social impacts of mining, which is not an option, especially in Europe and Austria.Due to these facts, there is a need for research on new and improved mining methods and planning, as well as on optimised processes and machinery. This article describes how the Chair of Mining Engineering and Mineral Economics at Montanuniversität Leoben intends to use these challenges as an opportunity with its updated strategy, both for research and for teaching. For the research area, sustainability and involvement in the shaping of raw materials policy should form the framework. With a focus on digitisation and underground mining as well as strengthening the areas of open-pit mining, conveying technology and geoinformatics, research is to be future-proofed for these upcoming transformations. Teaching will continue to include a basic engineering education with specialisation in mining, whereby digitalisation will play an increasingly strong role.

Pancolonic chromoendoscopy with indigo carmine versus standard colonoscopy for detection of neoplastic lesions: a randomised two-centre trial.

OBJECTIVE: Colonoscopy is the accepted gold standard for detecting colorectal adenomas, but the miss rate, especially for small and flat lesions, remains unacceptably high. The aim of this study was to determine whether enhanced mucosal contrast using pancolonic chromoendoscopy (PCC) allows higher rates of adenoma detection. METHODS: In a prospective, randomised two-centre trial, PCC (with 0.4% indigo carmine spraying during continuous extubation) was compared with standard colonoscopy (control group) in consecutive patients attending for routine colonoscopy. The histopathology of the lesions detected was confirmed by evaluating the endoscopic resection or biopsy specimens. RESULTS: A total of 1008 patients were included (496 in the PCC group, 512 in the control group). The patients' demographic characteristics and indications for colonoscopy were similar in the two groups. The proportion of patients with at least one adenoma was significantly higher in the PCC group (46.2%) than in the control group (36.3%; p = 0.002). Chromoendoscopy increased the overall detection rate for adenomas (0.95 vs 0.66 per patient), flat adenomas (0.56 vs 0.28 per patient) and serrated lesions (1.19 vs 0.49 per patient) (p < 0.001). There was a non-significant trend towards increased detection of advanced adenomas (103 vs 81; p = 0.067). Mean extubation times were slightly but significantly longer in the PCC group in comparison with the control group (11.6 ± 3.36 min vs 10.1 ± 2.03 min; p < 0.001). CONCLUSIONS: Pancolonic chromoendoscopy markedly enhances adenoma detection rates in an average-risk population and is practicable enough for routine application.

A Current Encyclopedia of Bioinformatics Tools, Data Formats and Resources for Mass Spectrometry Lipidomics.

Mass spectrometry is a widely used technology to identify and quantify biomolecules such as lipids, metabolites and proteins necessary for biomedical research. In this study, we catalogued freely available software tools, libraries, databases, repositories and resources that support lipidomics data analysis and determined the scope of currently used analytical technologies. Because of the tremendous importance of data interoperability, we assessed the support of standardized data formats in mass spectrometric (MS)-based lipidomics workflows. We included tools in our comparison that support targeted as well as untargeted analysis using direct infusion/shotgun (DI-MS), liquid chromatography-mass spectrometry, ion mobility or MS imaging approaches on MS1 and potentially higher MS levels. As a result, we determined that the Human Proteome Organization-Proteomics Standards Initiative standard data formats, mzML and mzTab-M, are already supported by a substantial number of recent software tools. We further discuss how mzTab-M can serve as a bridge between data acquisition and lipid bioinformatics tools for interpretation, capturing their output and transmitting rich annotated data for downstream processing. However, we identified several challenges of currently available tools and standards. Potential areas for improvement were: adaptation of common nomenclature and standardized reporting to enable high throughput lipidomics and improve its data handling. Finally, we suggest specific areas where tools and repositories need to improve to become FAIRer.

Water infusion for cecal intubation increases patient tolerance, but does not improve intubation of unsedated colonoscopies.

BACKGROUND & AIMS: Several studies have indicated that water infusion, instead of air insufflation, enhances cecal intubation in selected patients undergoing unsedated colonoscopy. We performed a prospective, randomized, controlled trial to investigate whether the water technique increases the proportion of patients that are able to complete unsedated colonoscopy. METHODS: We analyzed data from 116 consecutive outpatients who were willing to start colonoscopy without sedation; 58 were each randomly assigned to groups given water infusion or air insufflation during the insertion phase. Sedation and analgesia were administered on demand. RESULTS: Fewer patients requested sedation in the water group (8.6%) than in the air group (34.5%; P = .003) and their maximum pain scores were lower (2.8 ± 1.9 vs 4.2 ± 2.3 in the air group; P = .011). However, differences in percentages of patients who received complete, unsedated colonoscopy between the water group (74.1%) and air group (62.1%) did not reach statistical significance (P = .23); the percentage of successful cecal intubations was lower in the water group (82.8%) than in the air group (96.5%; P = .03) because of poor visibility. Failed procedures in the water group were completed successfully after air insufflation. The cecal intubation time was shorter in the air group (6.2 ± 3.4 min) than in the water group (8.1 ± 3.0 min; P = .01). CONCLUSIONS: In patients willing to undergo unsedated colonoscopy, water infusion improves patient tolerance for cecal intubation, compared with air insufflation. However, it does not increase the overall percentage of successful cecal intubations because suboptimal bowel preparation interferes with visibility.