New Approaches to Protein NMR Automation

The three-dimensional structure of a protein molecule is the key to understanding its biological and physiological properties. A major problem in bioinformatics is to efficiently determine the three-dimensional structures of query proteins. Protein NMR structure de- termination is one of the main experimental methods and is comprised of: (i) protein sample production and isotope labelling, (ii) collecting NMR spectra, and (iii) analysis of the spectra to produce the protein structure. In protein NMR, the three-dimensional struc- ture is determined by exploiting a set of distance restraints between spatially proximate atoms. Currently, no practical automated protein NMR method exists that is without human intervention. We first propose a complete automated protein NMR pipeline, which can efficiently be used to determine the structures of moderate sized proteins. Second, we propose a novel and efficient semidefinite programming-based (SDP) protein structure determination method. The proposed automated protein NMR pipeline consists of three modules: (i) an automated peak picking method, called PICKY, (ii) a backbone chemical shift assign- ment method, called IPASS, and (iii) a protein structure determination method, called FALCON-NMR. When tested on four real protein data sets, this pipeline can produce structures with reasonable accuracies, starting from NMR spectra. This general method can be applied to other macromolecule structure determination methods. For example, a promising application is RNA NMR-assisted secondary structure determination. In the second part of this thesis, due to the shortcomings of FALCON-NMR, we propose a novel SDP-based protein structure determination method from NMR data, called SPROS. Most of the existing prominent protein NMR structure determination methods are based on molecular dynamics coupled with a simulated annealing schedule. In these methods, an objective function representing the error between observed and given distance restraints is minimized; these objective functions are highly non-convex and difficult to optimize. Euclidean distance geometry methods based on SDP provide a natural formulation for realizing a three-dimensional structure from a set of given distance constraints. However, the complexity of the SDP solvers increases cubically with the input matrix size, i.e., the number of atoms in the protein, and the number of constraints. In fact, the complexity of SDP solvers is a major obstacle in their applicability to the protein NMR problem. To overcome these limitations, the SPROS method models the protein molecule as a set of intersecting two- and three-dimensional cliques. We adapt and extend a technique called semidefinite facial reduction for the SDP matrix size reduction, which makes the SDP problem size approximately one quarter of the original problem. The reduced problem is solved nearly one hundred times faster and is more robust against numerical problems. Reasonably accurate results were obtained when SPROS was applied to a set of 20 real protein data sets

Orientación sobre salud y seguridad en el trabajo. Diseño de sistemas de seguridad y extinción de incendios en redes de transporte ferroviario urbano

In this paper, considering the importance and safety status of urban train systems, we study and assess the urban management requirements and requirements for equipping the inner city network using the results of “cost-benefit” techniques in order to analyze the methods Fire control and fire, as well as the use of fire safety systems in the urban train network. On the other hand, the development of tools for measuring and comparing the effectiveness of fire prevention and fire prevention measures in various rail transportation systems, which are very useful in various safety engineering methods in the design of mass transportation systems such as LRT or tram. And can be effective in analyzing the fire safety of its systems.En este documento, considerando la importancia y el estado de seguridad de los sistemas de trenes urbanos, estudiamos y evaluamos los requisitos de gestión urbana y los requisitos para equipar la red de la ciudad utilizando los resultados de las técnicas de “costo-beneficio” para analizar los métodos de control de incendios y de incendios, así como el uso de sistemas de seguridad contra incendios en la red de trenes urbanos. Por otro lado, el desarrollo de herramientas para medir y comparar la efectividad de las medidas de prevención y prevención de incendios en varios sistemas de transporte ferroviario, que son muy útiles en diversos métodos de ingeniería de seguridad en el diseño de sistemas de transporte masivo como LRT o tranvía. Y puede ser eficaz en el análisis de la seguridad contra incendios de sus sistemas

Succinct dynamic de Bruijn graphs

Motivation: The de Bruijn graph is one of the fundamental data structures for analysis of high throughput sequencing data. In order to be applicable to population-scale studies, it is essential to build and store the graph in a space- and time-efficient manner. In addition, due to the ever-changing nature of population studies, it has become essential to update the graph after construction, e.g. add and remove nodes and edges. Although there has been substantial effort on making the construction and storage of the graph efficient, there is a limited amount of work in building the graph in an efficient and mutable manner. Hence, most space efficient data structures require complete reconstruction of the graph in order to add or remove edges or nodes. Results: In this article, we present DynamicBOSS, a succinct representation of the de Bruijn graph that allows for an unlimited number of additions and deletions of nodes and edges. We compare our method with other competing methods and demonstrate that DynamicBOSS is the only method that supports both addition and deletion and is applicable to very large samples (e.g. greater than 15 billion k-mers). Competing dynamic methods, e.g. FDBG cannot be constructed on large scale datasets, or cannot support both addition and deletion, e.g. BiFrost.Peer reviewe

Defensa pasiva: medición y evaluación de la vulnerabilidad urbana con un enfoque de resiliencia

The purpose of the present research is to measure the level of urban safety based on the principles of passive defense, urban leveling based on the degree of vulnerability, the urban infrastructure dispersal pattern and important decision-making organizations in the city. The study is based on the urban environment, which has been used to measure the vulnerability of the city during the onset of war by using spatial indices influencing safety.El propósito de la presente investigación es medir el nivel de seguridad urbana basado en los principios de defensa pasiva, la nivelación urbana basada en el grado de vulnerabilidad, el patrón de dispersión de la infraestructura urbana y las importantes organizaciones de toma de decisiones en la ciudad. El estudio se basa en el entorno urbano, que se ha utilizado para medir la vulnerabilidad de la ciudad durante el inicio de la guerra mediante el uso de índices espaciales que influyen en la seguridad

DeepSig: Deep learning improves signal peptide detection in proteins

Motivation: The identification of signal peptides in protein sequences is an important step toward protein localization and function characterization. Results: Here, we present DeepSig, an improved approach for signal peptide detection and cleavage-site prediction based on deep learning methods. Comparative benchmarks performed on an updated independent dataset of proteins show that DeepSig is the current best performing method, scoring better than other available state-of-the-art approaches on both signal peptide detection and precise cleavage-site identification. Availability and implementation: DeepSig is available as both standalone program and web server at https://deepsig.biocomp.unibo.it. All datasets used in this study can be obtained from the same website

Space-efficient merging of succinct de Bruijn graphs

We propose a new algorithm for merging succinct representations of de Bruijn graphs introduced in [Bowe et al. WABI 2012]. Our algorithm is based on the lightweight BWT merging approach by Holt and McMillan [Bionformatics 2014, ACM-BCB 2014]. Our algorithm has the same asymptotic cost of the state of the art tool for the same problem presented by Muggli et al. [bioRxiv 2017, Bioinformatics 2019], but it uses less than half of its working space. A novel important feature of our algorithm, not found in any of the existing tools, is that it can compute the Variable Order succinct representation of the union graph within the same asymptotic time/space bounds.Comment: Accepted to SPIRE'1

Widespread intron retention in mammals functionally tunes transcriptomes

© 2014 Braunschweig et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.Alternative splicing (AS) of precursor RNAs is responsible for greatly expanding the regulatory and functional capacity of eukaryotic genomes. Of the different classes of AS, intron retention (IR) is the least well understood. In plants and unicellular eukaryotes, IR is the most common form of AS, whereas in animals, it is thought to represent the least prevalent form. Using high-coverage poly(A)(+) RNA-seq data, we observe that IR is surprisingly frequent in mammals, affecting transcripts from as many as three-quarters of multiexonic genes. A highly correlated set of cis features comprising an "IR code" reliably discriminates retained from constitutively spliced introns. We show that IR acts widely to reduce the levels of transcripts that are less or not required for the physiology of the cell or tissue type in which they are detected. This "transcriptome tuning" function of IR acts through both nonsense-mediated mRNA decay and nuclear sequestration and turnover of IR transcripts. We further show that IR is linked to a cross-talk mechanism involving localized stalling of RNA polymerase II (Pol II) and reduced availability of spliceosomal components. Collectively, the results implicate a global checkpoint-type mechanism whereby reduced recruitment of splicing components coupled to Pol II pausing underlies widespread IR-mediated suppression of inappropriately expressed transcripts.This work was supported by grants from the Canadian Institutes of Health Research and Canadian Cancer Society (B.J.B.); EMBO long-term fellowships (U.B. and T.G.-P.); Human Frontier Science Program Organization long-term fellowships (U.B. and M.I.); an OSCI fellowship (T.G.-P.); CIHR postdoctoral and Marie Curie IOF fellowships (N.L.B.-M.); and an NSERC studentship (E.N.).info:eu-repo/semantics/publishedVersio