Search results for "structural"
showing 10 items of 5047 documents
Identification of control targets in Boolean molecular network models via computational algebra
2015
Motivation: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The pot…
Accelerating metagenomic read classification on CUDA-enabled GPUs.
2016
Metagenomic sequencing studies are becoming increasingly popular with prominent examples including the sequencing of human microbiomes and diverse environments. A fundamental computational problem in this context is read classification; i.e. the assignment of each read to a taxonomic label. Due to the large number of reads produced by modern high-throughput sequencing technologies and the rapidly increasing number of available reference genomes software tools for fast and accurate metagenomic read classification are urgently needed. We present cuCLARK, a read-level classifier for CUDA-enabled GPUs, based on the fast and accurate classification of metagenomic sequences using reduced k-mers (…
Deep learning models for bacteria taxonomic classification of metagenomic data.
2018
Background An open challenge in translational bioinformatics is the analysis of sequenced metagenomes from various environmental samples. Of course, several studies demonstrated the 16S ribosomal RNA could be considered as a barcode for bacteria classification at the genus level, but till now it is hard to identify the correct composition of metagenomic data from RNA-seq short-read data. 16S short-read data are generated using two next generation sequencing technologies, i.e. whole genome shotgun (WGS) and amplicon (AMP); typically, the former is filtered to obtain short-reads belonging to a 16S shotgun (SG), whereas the latter take into account only some specific 16S hypervariable regions.…
Iwr1 facilitates RNA polymerase II dynamics during transcription elongation.
2017
Iwr1 is an RNA polymerase II (RNPII) interacting protein that directs nuclear import of the enzyme which has been previously assembled in the cytoplasm. Here we present genetic and molecular evidence that links Iwr1 with transcription. Our results indicate that Iwr1 interacts with RNPII during elongation and is involved in the disassembly of the enzyme from chromatin. This function is especially important in resolving problems posed by damage-arrested RNPII, as shown by the sensitivity of iwr1 mutants to genotoxic drugs and the Iwr1's genetic interactions with RNPII degradation pathway mutants. Moreover, absence of Iwr1 causes genome instability that is enhanced by defects in the DNA repair…
VISMapper: ultra-fast exhaustive cartography of viral insertion sites for gene therapy
2017
The possibility of integrating viral vectors to become a persistent part of the host genome makes them a crucial element of clinical gene therapy. However, viral integration has associated risks, such as the unintentional activation of oncogenes that can result in cancer. Therefore, the analysis of integration sites of retroviral vectors is a crucial step in developing safer vectors for therapeutic use. Here we present VISMapper, a vector integration site analysis web server, to analyze next-generation sequencing data for retroviral vector integration sites. VISMapper can be found at: http://vismapper.babelomics.org . Because it uses novel mapping algorithms VISMapper is remarkably faster 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…
Closed-Locked and Apo-Resting State Structures of the Human α7 Nicotinic Receptor: A Computational Study
2018
International audience; Nicotinic acetylcholine receptors, belonging to the Cys-loop super-family of ligand-gated ion channels (LGICs), are membrane proteins present in neurons and at neuromuscular junctions. They are responsible for signal transmission, and their function is regulated by neurotransmitters, agonists and antagonists drugs. A detailed knowledge of their conformational transition in response to ligand binding is critical to understand the basis of ligand-receptor interaction, in view of new pharmacological approaches to control receptor activity. However, the scarcity of experimentally derived structures of human channels makes this perspective extremely challenging. To contri…
A possible desensitized state conformation of the human α7 nicotinic receptor: A molecular dynamics study
2017
International audience; The determination of the conformational states corresponding to diverse functional roles of ligand gated ion channels is subject of intense investigation with various techniques, from X-rays structure determination to electrophysiology and computational modeling. Even with a certain number of structures becoming recently available, only few major structural features distinguishing conductive open channel from the non conductive resting protein have been highlighted, while high-resolution details are still missing. The characterization of the desensitized conformation(s) is even more complex, and only few specific characteristics have been identified. Furthermore, exp…
Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwid…
2015
ABSTRACTThere is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. I…
Cbt modulates Foxo activation by positively regulating insulin signaling in Drosophila embryos.
2018
In late Drosophila embryos, the epidermis exhibits a dorsal hole as a consequence of germ band retraction. It is sealed during dorsal closure (DC), a morphogenetic process in which the two lateral epidermal layers converge towards the dorsal midline and fuse. We previously demonstrated the involvement of the Cbt transcription factor in Drosophila DC. However its molecular role in the process remained obscure. In this study, we used genomic approaches to identify genes regulated by Cbt as well as its direct targets during late embryogenesis. Our results reveal a complex transcriptional circuit downstream of Cbt and evidence that it is functionally related with the Insulin/insulin-like growth…