Prediction of gene essentiality using machine learning and genome-scale metabolic models

The identification of essential genes, i.e. those that impair cell survival when deleted, requires large growth assays of knock-out strains. The complexity and cost of such experiments has triggered a growing interest in computational methods for prediction of gene essentiality. In the case of metabolic genes, Flux Balance Analysis (FBA) is widely employed to predict essentiality under the assumption that cells maximize their growth rate. However, this approach assumes that knock-out strains optimize the same objectives as the wild-type, which excludes cases in which deletions cause large physiological changes to meet other objectives for survival. Here, we resolve this limitation with a novel machine learning approach that predicts essentiality directly from wild-type flux distributions. We first project the wild-type FBA solution onto a mass flow graph, a digraph with reactions as nodes and edge weights proportional to the mass transfer between reactions, and then train binary classifiers on the connectivity of graph nodes. We demonstrate the efficacy of this approach using the most complete metabolic model of Escherichia coli, achieving near state-of-the art prediction accuracy for essential genes. Our approach suggests that wild-type FBA solutions contain enough information to predict essentiality, without the need to assume optimality of deletion strains

Distributed search based on self-indexed compressed text

Query response times within a fraction of a second in Web search engines are feasible due to the use of indexing and caching techniques, which are devised for large text collections partitioned and replicated into a set of distributed-memory processors. This paper proposes an alternative query processing method for this setting, which is based on a combination of self-indexed compressed text and posting lists caching. We show that a text self-index (i.e., an index that compresses the text and is able to extract arbitrary parts of it) can be competitive with an inverted index if we consider the whole query process, which includes index decompression, ranking and snippet extraction time. The advantage is that within the space of the compressed document collection, one can carry out the posting lists generation, document ranking and snippet extraction. This significantly reduces the total number of processors involved in the solution of queries. Alternatively, for the same amount of hardware, the performance of the proposed strategy is better than that of the classical approach based on treating inverted indexes and corresponding documents as two separate entities in terms of processors and memory space.Fil: Arroyuelo, Diego. No especifíca;Fil: Gil Costa, Graciela Verónica. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; ArgentinaFil: González, Senén. No especifíca;Fil: Marin, Mauricio. Universidad de Santiago de Chile; ChileFil: Oyarzún, Mauricio. Universidad de Santiago de Chile; Chil

Otras formas de finalización del proceso de quiebra: análisis de la legislación vigente : El avenimiento

La obra desarrolla un análisis pormenorizado de la cuestión vinculada a las distintas formas de finalización en el proceso falencial de la quiebra en general, mas detalladamente el avenimiento en particular. En el mismo recorremos los distintos basamentos sobre uno de los modos de conclusión de la quiebra.Facultad de Ciencias Económica

Otras formas de finalización del proceso de quiebra: análisis de la legislación vigente : El avenimiento

La obra desarrolla un análisis pormenorizado de la cuestión vinculada a las distintas formas de finalización en el proceso falencial de la quiebra en general, mas detalladamente el avenimiento en particular. En el mismo recorremos los distintos basamentos sobre uno de los modos de conclusión de la quiebra.Facultad de Ciencias Económica

Computation of Single-Cell Metabolite Distributions Using Mixture Models

Metabolic heterogeneity is widely recognised as the next challenge in our understanding of non-genetic variation. A growing body of evidence suggests that metabolic heterogeneity may result from the inherent stochasticity of intracellular events. However, metabolism has been traditionally viewed as a purely deterministic process, on the basis that highly abundant metabolites tend to filter out stochastic phenomena. Here we bridge this gap with a general method for prediction of metabolite distributions across single cells. By exploiting the separation of time scales between enzyme expression and enzyme kinetics, our method produces estimates for metabolite distributions without the lengthy stochastic simulations that would be typically required for large metabolic models. The metabolite distributions take the form of Gaussian mixture models that are directly computable from single-cell expression data and standard deterministic models for metabolic pathways. The proposed mixture models provide a systematic method to predict the impact of biochemical parameters on metabolite distributions. Our method lays the groundwork for identifying the molecular processes that shape metabolic heterogeneity and its functional implications in disease.Comment: 5 Figures, 3 Table

Opportunities at the interface of network science and metabolic modeling

Metabolism plays a central role in cell physiology because it provides the molecular machinery for growth. At the genome-scale, metabolism is made up of thousands of reactions interacting with one another. Untangling this complexity is key to understand how cells respond to genetic, environmental, or therapeutic perturbations. Here we discuss the roles of two complementary strategies for the analysis of genome-scale metabolic models: Flux Balance Analysis (FBA) and network science. While FBA estimates metabolic flux on the basis of an optimization principle, network approaches reveal emergent properties of the global metabolic connectivity. We highlight how the integration of both approaches promises to deliver insights on the structure and function of metabolic systems with wide-ranging implications in discovery science, precision medicine and industrial biotechnology

Connexin and Pannexin-Based Channels in Oligodendrocytes: Implications in Brain Health and Disease

Oligodendrocytes are the myelin forming cells in the central nervous system (CNS). In addition to this main physiological function, these cells play key roles by providing energy substrates to neurons as well as information required to sustain proper synaptic transmission and plasticity at the CNS. The latter requires a fine coordinated intercellular communication with neurons and other glial cell types, including astrocytes. In mammals, tissue synchronization is mainly mediated by connexins and pannexins, two protein families that underpin the communication among neighboring cells through the formation of different plasma membrane channels. At one end, gap junction channels (GJCs; which are exclusively formed by connexins in vertebrates) connect the cytoplasm of contacting cells allowing electrical and metabolic coupling. At the other end, hemichannels and pannexons (which are formed by connexins and pannexins, respectively) communicate the intra- and extracellular compartments, serving as diffusion pathways of ions and small molecules. Here, we briefly review the current knowledge about the expression and function of hemichannels, pannexons and GJCs in oligodendrocytes, as well as the evidence regarding the possible role of these channels in metabolic and synaptic functions at the CNS. In particular, we focus on oligodendrocyte-astrocyte coupling during axon metabolic support and its implications in brain health and disease

Effect of cutting and storage temperature on Packham’s Triumph pears (Pyrus communis L.)

For the minimally processed (MP) fruit, the cutting type and temperature are the main factors in order to maintain good quality and appearance. The objective of this work was to evaluate the effects of cutting type and storage on the metabolic activity, color, firmness, aroma profile and, organic acid and sugar content of MP pears (Pyrus communis L. cv. Packham’s Triumph). Whole fruits were washed, peeled and cut in wedges or dice. Then, the pieces were packaged in plastic containers and stored 8 days at 5 or 8 ºC. The cutting type and storage temperature had an important effect on the physiological parameters, color, firmness and organic acid and sugar content. However, the aroma volatile content was reduced independently of the cutting type and the storage temperature. Therefore, the pear cultivar Packham’s Triumph should be cut in wedges and stored 8 d at 5º C to maintain an optimum global quality.En los frutos mínimamente procesados en fresco (MPF) el tipo de corte y la temperatura son factores por considerar para mantener una calidad y apariencia adecuada. El objetivo de este trabajo fue evaluar los efectos del corte y la temperatura de conservación sobre la actividad metabólica, color, firmeza, perfil aromático y concentración de ácidos orgánicos y azúcares de peras (Pyrus communis L. cv. Packham’s Triumph). Los frutos enteros fueron lavados, pelados, cortados en cascos o cubos, envasados en tarrinas y posteriormente almacenados 8 d a 5 o 8 ºC. El tipo de corte y la temperatura tuvieron un efecto significativo sobre los parámetros fisiológicos, color, firmeza y en el contenido de ácidos orgánicos y azúcares.  Sin embargo, el contenido de compuestos aromáticos volátiles se redujo independientemente del tipo de corte y las temperaturas de conservación. Por tanto, esta variedad de peras Packham’s Triumph deben ser procesadas en cascos y deben almacenarse a 5º C para mantener una calidad general óptima durante 8 días

Forest hydrology in Chile: Past, present, and future

This paper reviews the current knowledge of hydrological processes in Chilean temperate forests which extend along western South America from latitude 29° S to 56 ° S. This geographic region includes a diverse range of natural and planted forests and a broad sweep of vegetation, edaphic, topographic, geologic, and climatic settings which create a unique natural laboratory. Many local communities, endangered freshwater ecosystems, and downstream economic activities in Chile rely on water flows from forested catchments. This review aims to (i) provide a comprehensive overview of Chilean forest hydrology, to (ii) review prior research in forest hydrology in Chile, and to (iii) identify knowledge gaps and provide a vision for future research on forest hydrology in Chile. We reviewed the relation between native forests, commercial plantations, and other land uses on water yield and water quality from the plot to the catchment scale. Much of the global understanding of forests and their relationship with the water cycle is in line with the findings of the studies reviewed here. Streamflow from forested catchments increases after timber harvesting, native forests appear to use less water than plantations, and streams draining native forest yield less sediment than streams draining plantations or grassland/shrublands. We identified 20 key knowledge gaps such as forest groundwater systems, soil–plant-atmosphere interactions, native forest hydrology, and the effect of forest management and restoration on hydrology. Also, we found a paucity of research in the northern geographic areas and forest types (35-36 ° S); most forest hydrology studies in Chile (56 %) have been conducted in the southern area (Los Rios Region around 39-40 ° S). There is limited knowledge of the geology and soils in many forested areas and how surface and groundwater are affected by changes in land cover. There is an opportunity to advance our understanding using process-based investigations linking field studies and modeling. Through the establishment of a forest hydrology science “society” to coordinate efforts, regional and national-scale land use planning might be supported. Our review ends with a vision to advance a cross-scale collaborative effort to use new nation-wide catchment-scale networks Long-term Ecosystem Research (LTER) sites, to promote common and complementary techniques in these studies, and to conduct transdisciplinary research to advance sound and integrated planning of forest lands in Chile