Search results for "formation"
showing 10 items of 21020 documents
Feasibility of sample size calculation for RNA-seq studies
2017
Sample size calculation is a crucial step in study design but is not yet fully established for RNA sequencing (RNA-seq) analyses. To evaluate feasibility and provide guidance, we evaluated RNA-seq sample size tools identified from a systematic search. The focus was on whether real pilot data would be needed for reliable results and on identifying tools that would perform well in scenarios with different levels of biological heterogeneity and fold changes (FCs) between conditions. We used simulations based on real data for tool evaluation. In all settings, the six evaluated tools provided widely different answers, which were strongly affected by FC. Although all tools failed for small FCs, s…
Old meets new: Comparative examination of conventional and innovative RNA-based methods for body fluid identification of laundered seminal fluid stai…
2018
Abstract The knowledge about the type of the body fluid/tissue that contributed to a trace can provide contextual insight into crime scene reconstruction and connect a suspect or a victim to a crime scene. Especially in sexual assault cases, it is important to verify the presence of spermatozoa. Victims often tend to clean their underwear/bedding after a sexual assault. If they later decide to report the crime to the police, in our experience, investigators usually do not send laundered items for DNA examination, since they believe that analysis after washing is no longer promising. As not only the individualization of traces on laundered items could be important in court, but also the type…
Deciphering the functional role of spatial and temporal muscle synergies in whole-body movements
2018
AbstractVoluntary movement is hypothesized to rely on a limited number of muscle synergies, the recruitment of which translates task goals into effective muscle activity. In this study, we investigated how to analytically characterize the functional role of different types of muscle synergies in task performance. To this end, we recorded a comprehensive dataset of muscle activity during a variety of whole-body pointing movements. We decomposed the electromyographic (EMG) signals using a space-by-time modularity model which encompasses the main types of synergies. We then used a task decoding and information theoretic analysis to probe the role of each synergy by mapping it to specific task …
Access to new highly potent antileukemia, antiviral and antimalarial agents via hybridization of natural products (homo)egonol, thymoquinone and arte…
2018
Hybridization of natural products has high potential to further improve their activities and may produce synergistic effects between linked pharmacophores. Here we report synthesis of nine new hybrids of natural products egonol, homoegonol, thymoquinone and artemisinin and evaluation of their activities against P. falciparum 3D7 parasites, human cytomegalovirus, sensitive and multidrug-resistant human leukemia cells. Most of the new hybrids exceed their parent compounds in antimalarial, antiviral and antileukemia activities and in some cases show higher in vitro efficacy than clinically used reference drugs chloroquine, ganciclovir and doxorubicin. Combined, our findings stress the high pot…
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 …
The MDS and EVI1 complex locus (MECOM) isoforms regulate their own transcription and have different roles in the transformation of hematopoietic stem…
2016
Transcriptional activation of the EVI1 oncogene (3q26) leads to aggressive forms of human acute myeloid leukemia (AML). However, the mechanism of EVI1-mediated leukemogenesis has not been fully elucidated. Previously, by characterizing the EVI1 promoter, we have shown that RUNX1 and ELK1 directly regulate EVI1 transcription. Intriguingly, bioinformatic analysis of the EVI1 promoter region identified the presence of several EVI1 potential binding sites. Thus, we hypothesized that EVI1 could bind to these sites regulating its own transcription. In this study, we show that there is a functional interaction between EVI1 and its promoter, and that the different EVI1 isoforms (EVI1-145kDa, EVI1-Δ…
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…
Caretakers and Gatekeepers
2017
It has now been generally accepted that the genes responsible for familial cancer syndromes can be divided into two categories, known as caretakers and gatekeepers. Caretakers are genes that control the maintenance of the genetic information integrity in each cell while gatekeepers are those genes which directly regulate tumor growth, codifying for proteins which either stimulate or inhibit proliferation, differentiation or apoptosis. Keywords: gatekeeper genes; caretaker genes; tumor suppressor genes; cell cycle; hereditary syndromes
Lost Strings in Genomes: What Sense Do They Make?
2017
We studied the sets of avoided strings to be observed over a family of genomes. It was found that the length of the minimal avoided string rarely exceeds 9 nucleotides, with neither respect to a phylogeny of a genome under consideration. The lists of the avoided strings observed over the sets of (related) genomes have been analyzed. Very low correlation between the phylogeny, and the set of those strings has been found.