Search results for "COMPUTATION"

Use of deep learning methods to translate drug-induced gene expression changes from rat to human primary hepatocytes

2020

In clinical trials, animal and cell line models are often used to evaluate the potential toxic effects of a novel compound or candidate drug before progressing to human trials. However, relating the results of animal and in vitro model exposures to relevant clinical outcomes in the human in vivo system still proves challenging, relying on often putative orthologs. In recent years, multiple studies have demonstrated that the repeated dose rodent bioassay, the current gold standard in the field, lacks sufficient sensitivity and specificity in predicting toxic effects of pharmaceuticals in humans. In this study, we evaluate the potential of deep learning techniques to translate the pattern of …

Histone Deacetylase Inhibitors from Marine Invertebrates

2020

Simple Summary Histone deacetylases (HDACs) are enzymes that control gene expression and are involved in the onset of serious human pathologies, including cancer; hence, their inhibitors (HDACis) have received increased attention in recent years. It is known that marine invertebrates produce significant amounts of molecules showing active pharmacological properties and an extensive spectrum of biomedical applications. This review is focused on the description of the molecular, biochemical, and, where available, physiological aspects of marine invertebrate-derived compounds that possess HDACi properties, taking into consideration their possible utilization as treatment agents against differe…

MiasDB: A Database of Molecular Interactions Associated with Alternative Splicing of Human Pre-mRNAs.

2016

Alternative splicing (AS) is pervasive in human multi-exon genes and is a major contributor to expansion of the transcriptome and proteome diversity. The accurate recognition of alternative splice sites is regulated by information contained in networks of protein-protein and protein-RNA interactions. However, the mechanisms leading to splice site selection are not fully understood. Although numerous databases have been built to describe AS, molecular interaction databases associated with AS have only recently emerged. In this study, we present a new database, MiasDB, that provides a description of molecular interactions associated with human AS events. This database covers 938 interactions …

Common Hits Approach: Combining Pharmacophore Modeling and Molecular Dynamics Simulations.

2017

We present a new approach that incorporates flexibility based on extensive MD simulations of protein-ligand complexes into structure-based pharmacophore modeling and virtual screening. The approach uses the multiple coordinate sets saved during the MD simulations and generates for each frame a pharmacophore model. Pharmacophore models with the same pharmacophore features are pooled. In this way the high number of pharmacophore models that results from the MD simulation is reduced to only a few hundred representative pharmacophore models. Virtual screening runs are performed with every representative pharmacophore model; the screening results are combined and rescored to generate a single hi…

Measuring the clustering effect of BWT via RLE

2017

Abstract The Burrows–Wheeler Transform (BWT) is a reversible transformation on which are based several text compressors and many other tools used in Bioinformatics and Computational Biology. The BWT is not actually a compressor, but a transformation that performs a context-dependent permutation of the letters of the input text that often create runs of equal letters (clusters) longer than the ones in the original text, usually referred to as the “clustering effect” of BWT. In particular, from a combinatorial point of view, great attention has been given to the case in which the BWT produces the fewest number of clusters (cf. [5] , [16] , [21] , [23] ). In this paper we are concerned about t…

Comparison of CRISPR and Marker-Based Methods for the Engineering of Phage T7

2020

This article belongs to the Section Bacterial Viruses.

2016

RNA 2'-O-methylation is one of the ubiquitous nucleotide modifications found in many RNA types from Bacteria, Archaea and Eukarya. RNAs bearing 2'-O-methylations show increased resistance to degradation and enhanced stability in helices. While the exact role of each 2'-O-Me residue remained elusive, the catalytic protein Fibrillarin (Nop1 in yeast) responsible for 2'-O-methylation in eukaryotes, is associated with human pathologies. Therefore, there is an urgent need to precisely map and quantify hundreds of 2'-O-Me residues in RNA using high-throughput technologies. Here, we develop a reliable protocol using alkaline fragmentation of total RNA coupled to a commonly used ligation approach, …

2015

Alternative splicing is an important mechanism in eukaryotes that expands the transcriptome and proteome significantly. It plays an important role in a number of biological processes. Understanding its regulation is hence an important challenge. Recently, increasing evidence has been collected that supports an involvement of intragenic DNA methylation in the regulation of alternative splicing. The exact mechanisms of regulation, however, are largely unknown, and speculated to be complex: different methylation profiles might exist, each of which could be associated with a different regulation mechanism. We present a computational technique that is able to determine such stable methylation pa…

Zebrafish as a Model for the Study of Chaperonopathies

2016

There is considerable information on the clinical manifestations and mode of inheritance for many genetic chaperonopathies but little is known on the molecular mechanisms underlying the cell and tissue abnormalities that characterize them. This scarcity of knowledge is mostly due to the lack of appropriate animal models that mimic closely the human molecular, cellular, and histological characteristics. In this article we introduce zebrafish as a suitable model to study molecular and cellular mechanisms pertaining to human chaperonopathies. Genetic chaperonopathies manifest themselves from very early in life so it is necessary to examine the impact of mutant chaperone genes during developmen…

GIbPSs: a toolkit for fast and accurate analyses of genotyping-by-sequencing data without a reference genome.

2015

Genotyping-by-sequencing (GBS) and related methods are increasingly used for studies of non-model organisms from population genetic to phylogenetic scales. We present GIbPSs, a new genotyping toolkit for the analysis of data from various protocols such as RAD, double-digest RAD, GBS, and two-enzyme GBS without a reference genome. GIbPSs can handle paired-end GBS data and is able to assign reads from both strands of a restriction fragment to the same locus. GIbPSs is most suitable for population genetic and phylogeographic analyses. It avoids genotyping errors due to indel variation by identifying and discarding affected loci. GIbPSs creates a genotype database that offers rich functionality…