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// Tim Kehl 1, * , Christina Backes 2, * , Fabian Kern 2 , Tobias Fehlmann 2 , Nicole Ludwig 3 , Eckart Meese 3 , Hans-Peter Lenhof 1 and Andreas Keller 2, * 1 Center for Bioinformatics, Saarland University, Saarland Informatics Campus, Saarbrucken, Germany 2 Chair for Clinical Bioinformatics, Saarland University, Saarland Informatics Campus, Saarbrucken, Germany 3 Department of Human Genetics, Saarland University, Homburg, Germany * These authors have contributed equally to this work Correspondence to: Andreas Keller, email: andreas.keller@ccb.uni-saarland.de Keywords: non-coding RNA; systems biology; target gene; microRNA Received: July 27, 2017 Accepted: September 21, 2017 Published: November 09, 2017 ABSTRACT miRNAs are typically repressing gene expression by binding to the 3’ UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways. By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions. Respective results were obtained for both, predicted target genes as well as experimentally validated targets. We note that miRNAs target gene set similarity follows a bimodal distribution, pointing at a set of 282 miRNAs that seems to target genes with very high specificity. Further, we discuss miRNAs with different (seed) sequences that nonetheless regulate similar gene sets or pathways. Most intriguingly, we found miRNA pairs that regulate different gene sets but similar pathways such as miR-6886-5p and miR-3529-5p. These are jointly targeting different parts of the MAPK signaling cascade. The main goal of this study is to provide a general overview on the results, to highlight a selection of relevant results on miRNAs, miRNA seeds, target genes and target pathways and to raise awareness for artifacts in respective comparisons. The full set of information that allows to infer detailed results on each miRNA has been included in miRPathDB, the miRNA target pathway database ( https://mpd.bioinf.uni-sb.de ).

The continuous increase of available biological data as consequence of modern high-throughput technologies poses new challenges for analysis techniques and database applications. Especially for miRNAs, one class of small non-coding RNAs, many algorithms have been developed to predict new candidates from next-generation sequencing data. While the amount of publications describing novel miRNA candidates keeps steadily increasing, the current gold standard database for miRNAs - miRBase - has not been updated since June 2014. As a result, publications describing new miRNA candidates in the last three to five years might have a substantial overlap of candidates without noticing. With miRCarta we implemented a database to collect novel miRNA candidates and augment the information provided by miRBase. In the first stage, miRCarta is thought to be a highly sensitive collection of potential miRNA candidates with a high degree of analysis functionality, annotations and details on each miRNA. We added—besides the full content of the miRBase—12,857 human miRNA precursors to miRCarta. Users can match their own predictions to the entries of miRCarta to reduce potential redundancies in their studies. miRCarta provides the most comprehensive collection of human miRNAs and miRNA candidates to form a basis for further refinement and validation studies. The database is freely accessible at https://mircarta.cs.uni-saarland.de/.

The state-of-the-art blood pressure measurement is beside common cuff-based methods the cuff-less estimation of pulse-transit-time, which is the time a blood pressure wave requires to travel from left ventricle of the heart to another peripheral point in the cardiovascular system. Within this work we present a novel estimation method for cuff-less blood pressure measurement by analysing a single photoplethysmographic signal in the frequency domain. The harmonic phase-shift of the fundamental frequency and the first harmonic within the photoplethysmographic signal has proven a strong correlation of r = 0.8514 and r = 0.9315 with systolic and diastolic blood pressure respectively.

Following political strategy changes with the goal to reduce greenhouse gas emissions, the German power system has experienced a great penetration of intermittent renewable energy sources. The volatile electricity generation of renewable energy sources requires greater flexibility not only on the electricity supply but also on the demand side. The ventilation of buildings represents a largely untapped resource for demand response measures such as control reserve. Due to the quick reaction speed and inertia of the air balance of supplied buildings, electric motors of air handling units qualify to provide frequency containment reserve. In this paper we present a system architecture according to standards by the German transmission system operators to provide frequency containment reserve with an aggregate of air handling units. At an industrial site containing workshop and office buildings a prototype of the system has been installed and prequalified by the transmission system operators to provide almost 300 kW of frequency containment reserve.

Web repositories for almost all ‘omics’ types have been generated—detailing the repertoire of representatives across different tissues or cell types. A logical next step is the combination of these valuable sources. With IMOTA (interactive multi omics tissue atlas), we developed a database that includes 23 725 relations between miRNAs and 23 tissues, 310 932 relations between mRNAs and the same tissues as well as 63 043 relations between proteins and the 23 tissues in Homo sapiens. IMOTA also contains data on tissue-specific interactions, e.g. information on 331 413 miRNAs and target gene pairs that are jointly expressed in the considered tissues. By using intuitive filter and visualization techniques, it is with minimal effort possible to answer various questions. These include rather general questions but also requests specific for genes, miRNAs or proteins. An example for a general task could be ‘identify all miRNAs, genes and proteins in the lung that are highly expressed and where experimental evidence proves that the miRNAs target the genes’. An example for a specific request for a gene and a miRNA could for example be ‘In which tissues is miR-34c and its target gene BCL2 expressed?’. The IMOTA repository is freely available online at https://ccb-web.cs.uni-saarland.de/imota/.

Multiple studies endorsed the positive effect of regular exercise on mental and physical health. However, the molecular mechanisms underlying training-induced fitness in combination with personal life-style remain largely unexplored. Circulating biomarkers such as microRNAs (miRNAs) offer themselves for studying systemic and cellular changes since they can be collected from the bloodstream in a low-invasive manner. In Homo sapiens miRNAs are known to regulate a substantial number of protein-coding genes in a post-transcriptional manner and hence are of great interest to understand differential gene expression profiles, offering a cost-effective mechanism to study molecular training adaption, and connecting the dots from genomics to observed phenotypes. Here, we investigated molecular expression patterns of 2549 miRNAs in whole-blood samples from 23 healthy and untrained adult participants of a cross-over study, consisting of eight weeks of endurance training, with several sessions per week, followed by 8 weeks of washout and another 8 weeks of running, using microarrays. Participants were randomly assigned to one of the two study groups, one of which administered carbohydrates before each session in the first training period, and switching the treatment group for the second training period. During running sessions clinical parameters as heartbeat frequency were recorded. This information was extended with four measurements of maximum oxygen uptake (VO 2 max) for each participant. We observed that multiple circulating miRNAs show expression changes after endurance training, leveraging the capability to separate the blood samples by training status. To this end, we demonstrate that most of the variance in miRNA expression can be explained by both common and known biological and technical factors. Our findings highlight six distinct clusters of miRNAs, each exhibiting an oscillating expression profile across the four study timepoints, that can effectively be utilized to predict phenotypic VO 2 max levels. In addition, we identified miR-532-5p as a candidate marker to determine personal alterations in physical training performance on a case-by-case analysis taking the influence of a carbohydrate-rich nutrition into account. In literature, miR-532-5p is known as a common down-regulated miRNA in diabetes and obesity, possibly providing a molecular link between cellular homeostasis, personal fitness levels, and health in aging. We conclude that circulating miRNA expression can be altered due to regular endurance training, independent of the carbohydrate (CHO) availability in the training timeframe. Further validation studies are required to confirm the role of exercise-affected miRNAs and the extraordinary function of miR-532-5p in modulating the metabolic response to a high availability of glucose.

Motivation Since the initial discovery of microRNAs as post-transcriptional, regulatory key players in the 1990s, a total number of $2656$ mature microRNAs have been publicly described for Homo sapiens. As discovery of new miRNAs is still on-going, target identification remains to be an essential and challenging step preceding functional annotation analysis. One key challenge for researchers seems to be the selection of the most appropriate tool out of the larger multiverse of published solutions for a given research study set-up. Results In this review we collectively describe the field of in silico target prediction in the course of time and point out long withstanding principles as well as recent developments. By compiling a catalog of characteristics about the 98 prediction methods and identifying common and exclusive traits, we signpost a simplified mechanism to address the problem of application selection. Going further we devised interpretation strategies for common types of output as generated by frequently used computational methods. To this end, our work specifically aims to make prospective users aware of common mistakes and practical questions that arise during the application of target prediction tools. Availability An interactive implementation of our recommendations including materials shown in the manuscript is freely available at https://www.ccb.uni-saarland.de/mtguide.

Summary Prediction of transcription factor (TF) binding from epigenetics data and integrative analysis thereof are challenging. Here, we present TEPIC 2 a framework allowing for fast, accurate and versatile prediction, and analysis of TF binding from epigenetics data: it supports 30 species with binding motifs, computes TF gene and scores up to two orders of magnitude faster than before due to improved implementation, and offers easy-to-use machine learning pipelines for integrated analysis of TF binding predictions with gene expression data allowing the identification of important TFs. Availability and implementation TEPIC is implemented in C++, R, and Python. It is freely available at https://github.com/SchulzLab/TEPIC and can be used on Linux based systems. Supplementary information Supplementary data are available at Bioinformatics online.

Blood-borne small non-coding (sncRNAs) are among the prominent candidates for blood-based diagnostic tests. Often, high-throughput approaches are applied to discover biomarker signatures. These have to be validated in larger cohorts and evaluated by adequate statistical learning approaches. Previously, we published high-throughput sequencing based microRNA (miRNA) signatures in Alzheimer’s disease (AD) patients in the United States (US) and Germany. Here, we determined abundance levels of 21 known circulating miRNAs in 465 individuals encompassing AD patients and controls by RT-qPCR. We computed models to assess the relation between miRNA expression and phenotypes, gender, age, or disease severity (Mini-Mental State Examination; MMSE). Of the 21 miRNAs, expression levels of 20 miRNAs were consistently de-regulated in the US and German cohorts. 18 miRNAs were significantly correlated with neurodegeneration (Benjamini-Hochberg adjusted P

The increasing share of volatile renewable energy sources leads to new challenges for the power system. Flexible operation of power consumers is getting more important to keep power generation in balance with power consumption. Large potential loads are available in the industrial sector. Flexibility of these large loads is hard to utilize and requires consideration of the specific operational constraints. In the automotive industry test rigs for the development of cars or components, like engine or gearbox, exist, which are characterized by a high energy demand. In this work the idea of an energy-aware scheduling concept for test rigs in the automotive industry is presented. The goal is to provide an optimized schedule based on internal (e. g., prediction of local power generation) or external (e. g., electricity prices) signals. To this end, a methodological approach for the classification, identification and selection of suitable test rigs is presented. Based on this, a model of the test rigs has to be developed which can be used in a simulation to evaluate the optimization algorithm. Finally, the need for design guidelines for the implementation of an energy-aware test rig scheduling in a real-world evaluation environment are discussed.

Breast cancer is a heterogeneous disease with distinct molecular subtypes including the aggressive subtype triple-negative breast cancer (TNBC). We compared blood-borne miRNA signatures of early-stage basal-like (cytokeratin-CK5-positive) TNBC patients to age-matched controls. The miRNAs of TNBC patients were assessed prior to and following platinum-based neoadjuvant chemotherapy (NCT). After an exploratory genome-wide study on 21 cases and 21 controls using microarrays, the identified signatures were verified independently in two laboratories on the same and a new cohort by RT-qPCR. We differentiated the blood of TNBC patients before NCT from controls with 84% sensitivity. The most significant miRNA for this diagnostic classification was miR-126-5p (two tailed t-test p-value of 1.4 × 10−5). Validation confirmed the microarray results for all tested miRNAs. Comparing cancer patients prior to and post NCT highlighted 321 significant miRNAs (among them miR-34a, p-value of 1.2 × 10−23). Our results also suggest that changes in miRNA expression during NCT may have predictive potential to predict pathological complete response (pCR). In conclusion we report that miRNA expression measured from blood facilitates early and minimally-invasive diagnosis of basal-like TNBC. We also demonstrate that NCT has a significant influence on miRNA expression. Finally, we show that blood-borne miRNA profiles monitored over time have potential to predict pCR.

A four-month-old male fox shot dead by a hunter was subjected to unenhanced postmortem computed tomography (PMCT), PMCT-angiography (PMCTA) and magnetic resonance imaging (PMMR) to document the effects of semi-jacketed hunting ammunition (.17 Hornet) on the body of a small animal. The effect of the ammunition on bone structures (crushing of the cervical spine and spinal cord), blood vessels (laceration of all supra-aortal vessels) and surrounding soft tissue (large wound cavity) was extensive, and imaging confirmed the fatal power of the ammunition. Virtual autopsy (Virtopsy) is a valuable examination tool for veterinary indications as well as in humans.

The FZI House of Living Labs is a research and demonstration environment that facilitates interdisciplinary research, development, and evaluation in real-life scenarios. It consists of various Living Labs addressing different research topics. In the Living Lab smartEnergy, solutions for the energy system of the future are investigated. For this reason, the whole FZI House of Living Labs has been equipped with building automation, distributed generation, thermal and electrical storage, and technologies that enable the flexibilization of energy supply and demand. The equipment, among others, includes a photovoltaic and battery storage system, a micro combined heat and power plant, and an adsorption chiller. A building energy management system was developed that integrates various communication technologies, and hence enables monitoring, data recording, visualization, and the integrated optimization of the devices and systems. This way, flexibilities can be utilized with regard to different optimization goals such as an increased self-consumption, or the provisioning of grid-supporting services.