Search results for " Cluster"
showing 10 items of 2162 documents
Pharmacogenomics of Scopoletin in Tumor Cells
2016
Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS onc…
Innovative Strategies to Develop Chemical Categories Using a Combination of Structural and Toxicological Properties.
2016
Interest is increasing in the development of non-animal methods for toxicological evaluations. These methods are however, particularly challenging for complex toxicological endpoints such as repeated dose toxicity. European Legislation, e.g., the European Union's Cosmetic Directive and REACH, demands the use of alternative methods. Frameworks, such as the Read-across Assessment Framework or the Adverse Outcome Pathway Knowledge Base, support the development of these methods. The aim of the project presented in this publication was to develop substance categories for a read-across with complex endpoints of toxicity based on existing databases. The basic conceptual approach was to combine str…
Identification of a large, fast-expanding HIV-1 subtype B transmission cluster among MSM in Valencia, Spain
2017
We describe and characterize an exceptionally large HIV-1 subtype B transmission cluster occurring in the Comunidad Valenciana (CV, Spain). A total of 1806 HIV-1 protease-reverse transcriptase (PR/RT) sequences from different patients were obtained in the CV between 2004 and 2014. After subtyping and generating a phylogenetic tree with additional HIV-1 subtype B sequences, a very large transmission cluster which included almost exclusively sequences from the CV was detected (n = 143 patients). This cluster was then validated and characterized with further maximum-likelihood phylogenetic analyses and Bayesian coalescent reconstructions. With these analyses, the CV cluster was delimited to 11…
Regulatory effects of simvastatin and apoJ on APP processing and amyloid-beta clearance in blood-brain barrier endothelial cells
2017
Amyloid-β peptides (Aβ) accumulate in cerebral capillaries indicating a central role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer’s disease (AD). Although a relationship between apolipoprotein-, cholesterol- and Aβ metabolism is evident, the interconnecting mechanisms operating in brain capillary endothelial cells (BCEC) are poorly understood. ApoJ (clusterin) is present in HDL that regulates cholesterol metabolism which is disturbed in AD. ApoJ levels are increased in AD brains and in plasma of cerebral amyloid angiopathy (CAA) patients. ApoJ may bind, prevent fibrillization, and enhance clearance of Aβ. We here define a connection of apoJ and cellular cholesterol home…
parSRA: A framework for the parallel execution of short read aligners on compute clusters
2018
The growth of next generation sequencing datasets poses as a challenge to the alignment of reads to reference genomes in terms of both accuracy and speed. In this work we present parSRA, a parallel framework to accelerate the execution of existing short read aligners on distributed-memory systems. parSRA can be used to parallelize a variety of short read alignment tools installed in the system without any modification to their source code. We show that our framework provides good scalability on a compute cluster for accelerating the popular BWA-MEM and Bowtie2 aligners. On average, it is able to accelerate sequence alignments on 16 64-core nodes (in total, 1024 cores) with speedup of 10.48 …
CUDA-enabled hierarchical ward clustering of protein structures based on the nearest neighbour chain algorithm
2015
Clustering of molecular systems according to their three-dimensional structure is an important step in many bioinformatics workflows. In applications such as docking or structure prediction, many algorithms initially generate large numbers of candidate poses (or decoys), which are then clustered to allow for subsequent computationally expensive evaluations of reasonable representatives. Since the number of such candidates can easily range from thousands to millions, performing the clustering on standard central processing units (CPUs) is highly time consuming. In this paper, we analyse and evaluate different approaches to parallelize the nearest neighbour chain algorithm to perform hierarc…
panISa: ab initio detection of insertion sequences in bacterial genomes from short read sequence data.
2018
Abstract Motivation The advent of next-generation sequencing has boosted the analysis of bacterial genome evolution. Insertion sequence (IS) elements play a key role in prokaryotic genome organization and evolution, but their repetitions in genomes complicate their detection from short-read data. Results PanISa is a software pipeline that identifies IS insertions ab initio in bacterial genomes from short-read data. It is a highly sensitive and precise tool based on the detection of read-mapping patterns at the insertion site. PanISa performs better than existing IS detection systems as it is based on a database-free approach. We applied it to a high-risk clone lineage of the pathogenic spec…
Simulation-based estimation of branching models for LTR retrotransposons
2017
Abstract Motivation LTR retrotransposons are mobile elements that are able, like retroviruses, to copy and move inside eukaryotic genomes. In the present work, we propose a branching model for studying the propagation of LTR retrotransposons in these genomes. This model allows us to take into account both the positions and the degradation level of LTR retrotransposons copies. In our model, the duplication rate is also allowed to vary with the degradation level. Results Various functions have been implemented in order to simulate their spread and visualization tools are proposed. Based on these simulation tools, we have developed a first method to evaluate the parameters of this propagation …
Prospects and challenges for computer simulations of monolayer-protected metal clusters
2021
Precise knowledge of chemical composition and atomic structure of functional nanosized systems, such as metal clusters stabilized by an organic molecular layer, allows for detailed computational work to investigate structure-property relations. Here, we discuss selected recent examples of computational work that has advanced understanding of how these clusters work in catalysis, how they interact with biological systems, and how they can make self-assembled, macroscopic materials. A growing challenge is to develop effective new simulation methods that take into account the cluster-environment interactions. These new hybrid methods are likely to contain components from electronic structure t…
Parallel algorithms for large-scale biological sequence alignment on Xeon-Phi based clusters
2016
Computing alignments between two or more sequences are common operations frequently performed in computational molecular biology. The continuing growth of biological sequence databases establishes the need for their efficient parallel implementation on modern accelerators. This paper presents new approaches to high performance biological sequence database scanning with the Smith-Waterman algorithm and the first stage of progressive multiple sequence alignment based on the ClustalW heuristic on a Xeon Phi-based compute cluster. Our approach uses a three-level parallelization scheme to take full advantage of the compute power available on this type of architecture; i.e. cluster-level data par…