14 research outputs found

    Simulation of Flood Scenarios with Combined 2D/3D Numerical Models

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    Mini-Symposium: CFD in the Nearfield of Structure

    Simultaneous regression and classification for drug sensitivity prediction using an advanced random forest method

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    Machine learning methods trained on cancer cell line panels are intensively studied for the prediction of optimal anti-cancer therapies. While classifcation approaches distinguish efective from inefective drugs, regression approaches aim to quantify the degree of drug efectiveness. However, the high specifcity of most anti-cancer drugs induces a skewed distribution of drug response values in favor of the more drug-resistant cell lines, negatively afecting the classifcation performance (class imbalance) and regression performance (regression imbalance) for the sensitive cell lines. Here, we present a novel approach called SimultAneoUs Regression and classifcatiON Random Forests (SAURON-RF) based on the idea of performing a joint regression and classifcation analysis. We demonstrate that SAURON-RF improves the classifcation and regression performance for the sensitive cell lines at the expense of a moderate loss for the resistant ones. Furthermore, our results show that simultaneous classifcation and regression can be superior to regression or classifcation alone

    GeneTrail 3: advanced high-throughput enrichment analysis

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    We present GeneTrail 3, a major extension of our web service GeneTrail that offers rich functionality for the identification, analysis, and visualization of deregulated biological processes. Our web service provides a comprehensive collection of biological processes and signaling pathways for 12 model organisms that can be analyzed with a powerful framework for enrichment and network analysis of transcriptomic, miRNomic, proteomic, and genomic data sets. Moreover, GeneTrail offers novel workflows for the analysis of epigenetic marks, time series experiments, and single cell data. We demonstrate the capabilities of our web service in two case-studies, which highlight that GeneTrail is well equipped for uncovering complex molecular mechanisms. GeneTrail is freely accessible at: http://genetrail.bioinf.uni-sb.de

    REGGAE: a novel approach for the identification of key transcriptional regulators

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    Motivation: Transcriptional regulators play a major role in most biological processes. Alterations in their activities are associated with a variety of diseases and in particular with tumor development and progres sion. Hence, it is important to assess the effects of deregulated regulators on pathological processes. Results: Here, we present REGulator-Gene Association Enrichment (REGGAE), a novel method for the identification of key transcriptional regulators that have a significant effect on the expression of a given set of genes, e.g. genes that are differentially expressed between two sample groups. REGGAE uses a Kolmogorov–Smirnov-like test statistic that implicitly combines associations be tween regulators and their target genes with an enrichment approach to prioritize the influence of transcriptional regulators. We evaluated our method in two different application scenarios, which demonstrate that REGGAE is well suited for uncovering the influence of transcriptional regulators and is a valuable tool for the elucidation of complex regulatory mechanisms

    ClinOmicsTrailbc: a visual analytics tool for breast cancer treatment stratification

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    Motivation: Breast cancer is the second leading cause of cancer death among women. Tumors, even of the same histopathological subtype, exhibit a high genotypic diversity that impedes therapy stratification and that hence must be accounted for in the treatment decision-making process. Results: Here, we present ClinOmicsTrailbc, a comprehensive visual analytics tool for breast cancer decision support that provides a holistic assessment of standard-of-care targeted drugs, candidates for drug repositioning and immunotherapeutic approaches. To this end, our tool analyzes and visualizes clinical markers and (epi-)genomics and transcriptomics datasets to identify and evaluate the tumor’s main driver mutations, the tumor mutational burden, activity patterns of core cancerrelevant pathways, drug-specific biomarkers, the status of molecular drug targets and pharmacogenomic influences. In order to demonstrate ClinOmicsTrailbc’s rich functionality, we present three case studies highlighting various ways in which ClinOmicsTrailbc can support breast cancer precision medicine. ClinOmicsTrailbc is a powerful integrated visual analytics tool for breast cancer research in general and for therapy stratification in particular, assisting oncologists to find the best possible treatment options for their breast cancer patients based on actionable, evidence-based results. Availability and implementation: ClinOmicsTrailbc can be freely accessed at https://clinomicstrail. bioinf.uni-sb.de
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