Toll Based Measures for Dynamical Graphs

Biological networks are one of the most studied object in computational biology. Several methods have been developed for studying qualitative properties of biological networks. Last decade had seen the improvement of molecular techniques that make quantitative analyses reachable. One of the major biological modelling goals is therefore to deal with the quantitative aspect of biological graphs. We propose a probabilistic model that suits with this quantitative aspects. Our model combines graph with several dynamical sources. It emphazises various asymptotic statistical properties that might be useful for giving biological insightsComment: 11 page

Integrating heterogeneous knowledges for understanding biological behaviors: a probabilistic approach

Despite recent molecular technique improvements, biological knowledge remains incomplete. Reasoning on living systems hence implies to integrate heterogeneous and partial informations. Although current investigations successfully focus on qualitative behaviors of macromolecular networks, others approaches show partial quantitative informations like protein concentration variations over times. We consider that both informations, qualitative and quantitative, have to be combined into a modeling method to provide a better understanding of the biological system. We propose here such a method using a probabilistic-like approach. After its exhaustive description, we illustrate its advantages by modeling the carbon starvation response in Escherichia coli. In this purpose, we build an original qualitative model based on available observations. After the formal verification of its qualitative properties, the probabilistic model shows quantitative results corresponding to biological expectations which confirm the interest of our probabilistic approach.Comment: 10 page

Contributions des entrées sur les sorties pour les réseaux métaboliques sur génomes entiers: performances et utilisation pour des études en nutrition humaine

International audienceMetabolic networks are composed by all the biochemical reactions that can take place within an organism, as well as the exchanges of metabolites between the organism and its environment. The metabolic network of many organisms has been reconstructed, either manually or automatically, including at the scale of the entire genome. These models are stored in biological reference databases. Diets can be applied to these networks to model the behavior of organisms, when subjected to a specific diet. In this work, we automate an approach that allows, for each input nutrient in the network, to determine the percentages that are distributed in the different outputs when the organism is forced to evolve in a given diet. We name this approach nAIO (normalized Allocation of inputs on outputs. The nAIO is computed thanks to the inversion of a large-scale matrix and is combined with linear optimization problems. We apply this calculation to all known bacterial networks from studies of the gut microbiota and stored in the Virtual Metabolic Human database. The calculation of nAIOs shows that computation times do not depend on the size of the network but rather on the selected diet. The nAIO calculation also shows that for some bacteria the nAIOsare independent of diet. For these bacteria the nAIOs can be used to make predictions that resultin a linear relationship between the inputs of the system and its outputs

Stochastic frontier approach and data envelopment analysis to total factor productivity and efficiency measurement of Bangladeshi rice

The objective of this paper is to apply the Translog Stochastic Frontier production model (SFA) and Data Envelopment Analysis (DEA) to estimate efficiencies over time and the Total Factor Productivity (TFP) growth rate for Bangladeshi rice crops (Aus, Aman and Boro) throughout the most recent data available comprising the period 1989–2008. Results indicate that technical efficiency was observed as higher for Boro among the three types of rice, but the overall technical efficiency of rice production was found around 50%. Although positive changes exist in TFP for the sample analyzed, the average growth rate of TFP for rice production was estimated at almost the same levels for both Translog SFA with half normal distribution and DEA. Estimated TFP from SFA is forecasted with ARIMA (2, 0, 0) model. ARIMA (1, 0, 0) model is used to forecast TFP of Aman from DEA estimation

Predicting weighted unobserved nodes in a regulatory network using answer set programming.

peer reviewed[en] BACKGROUND: The impact of a perturbation, over-expression, or repression of a key node on an organism, can be modelled based on a regulatory and/or metabolic network. Integration of these two networks could improve our global understanding of biological mechanisms triggered by a perturbation. This study focuses on improving the modelling of the regulatory network to facilitate a possible integration with the metabolic network. Previously proposed methods that study this problem fail to deal with a real-size regulatory network, computing predictions sensitive to perturbation and quantifying the predicted species behaviour more finely. RESULTS: To address previously mentioned limitations, we develop a new method based on Answer Set Programming, MajS. It takes a regulatory network and a discrete partial set of observations as input. MajS tests the consistency between the input data, proposes minimal repairs on the network to establish consistency, and finally computes weighted and signed predictions over the network species. We tested MajS by comparing the HIF-1 signalling pathway with two gene-expression datasets. Our results show that MajS can predict 100% of unobserved species. When comparing MajS with two similar (discrete and quantitative) tools, we observed that compared with the discrete tool, MajS proposes a better coverage of the unobserved species, is more sensitive to system perturbations, and proposes predictions closer to real data. Compared to the quantitative tool, MajS provides more refined discrete predictions that agree with the dynamic proposed by the quantitative tool. CONCLUSIONS: MajS is a new method to test the consistency between a regulatory network and a dataset that provides computational predictions on unobserved network species. It provides fine-grained discrete predictions by outputting the weight of the predicted sign as a piece of additional information. MajS' output, thanks to its weight, could easily be integrated with metabolic network modelling

Toward systems biology in brown algae to explore acclimation and adaptation to the shore environment.

International audienceBrown algae belong to a phylogenetic lineage distantly related to land plants and animals. They are almost exclusively found in the intertidal zone, a harsh and frequently changing environment where organisms are submitted to marine and terrestrial constraints. In relation with their unique evolutionary history and their habitat, they feature several peculiarities, including at the level of their primary and secondary metabolism. The establishment of Ectocarpus siliculosus as a model organism for brown algae has represented a framework in which several omics techniques have been developed, in particular, to study the response of these organisms to abiotic stresses. With the recent publication of medium to high throughput profiling data, it is now possible to envision integrating observations at the cellular scale to apply systems biology approaches. As a first step, we propose a protocol focusing on integrating heterogeneous knowledge gained on brown algal metabolism. The resulting abstraction of the system will then help understanding how brown algae cope with changes in abiotic parameters within their unique habitat, and to decipher some of the mechanisms underlying their (1) acclimation and (2) adaptation, respectively consequences of (1) the behavior or (2) the topology of the system resulting from the integrative approach

Probabilistic Modeling of Microbial Metabolic Networks for Integrating Partial Quantitative Knowledge Within the Nitrogen Cycle

Understanding the interactions between microbial communities and their environment sufficiently to predict diversity on the basis of physicochemical parameters is a fundamental pursuit of microbial ecology that still eludes us. However, modeling microbial communities is problematic, because (i) communities are complex, (ii) most descriptions are qualitative, and (iii) quantitative understanding of the way communities interact with their surroundings remains incomplete. One approach to overcoming such complications is the integration of partial qualitative and quantitative descriptions into more complex networks. Here we outline the development of a probabilistic framework, based on Event Transition Graph (ETG) theory, to predict microbial community structure across observed chemical data. Using reverse engineering, we derive probabilities from the ETG that accurately represent observations from experiments and predict putative constraints on communities within dynamic environments. These predictions can feedback into the future development of field experiments by emphasizing the most important functional reactions, and associated microbial strains, required to characterize microbial ecosystems

Quantifying loopy network architectures

Biology presents many examples of planar distribution and structural networks having dense sets of closed loops. An archetype of this form of network organization is the vasculature of dicotyledonous leaves, which showcases a hierarchically-nested architecture containing closed loops at many different levels. Although a number of methods have been proposed to measure aspects of the structure of such networks, a robust metric to quantify their hierarchical organization is still lacking. We present an algorithmic framework, the hierarchical loop decomposition, that allows mapping loopy networks to binary trees, preserving in the connectivity of the trees the architecture of the original graph. We apply this framework to investigate computer generated graphs, such as artificial models and optimal distribution networks, as well as natural graphs extracted from digitized images of dicotyledonous leaves and vasculature of rat cerebral neocortex. We calculate various metrics based on the Asymmetry, the cumulative size distribution and the Strahler bifurcation ratios of the corresponding trees and discuss the relationship of these quantities to the architectural organization of the original graphs. This algorithmic framework decouples the geometric information (exact location of edges and nodes) from the metric topology (connectivity and edge weight) and it ultimately allows us to perform a quantitative statistical comparison between predictions of theoretical models and naturally occurring loopy graphs.Comment: 17 pages, 8 figures. During preparation of this manuscript the authors became aware of the work of Mileyko at al., concurrently submitted for publicatio

Integrating evolution into ecological modelling: accommodating phenotypic changes in agent based models.

PMCID: PMC3733718This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Evolutionary change is a characteristic of living organisms and forms one of the ways in which species adapt to changed conditions. However, most ecological models do not incorporate this ubiquitous phenomenon. We have developed a model that takes a 'phenotypic gambit' approach and focuses on changes in the frequency of phenotypes (which differ in timing of breeding and fecundity) within a population, using, as an example, seasonal breeding. Fitness per phenotype calculated as the individual's contribution to population growth on an annual basis coincide with the population dynamics per phenotype. Simplified model variants were explored to examine whether the complexity included in the model is justified. Outputs from the spatially implicit model underestimated the number of individuals across all phenotypes. When no phenotype transitions are included (i.e. offspring always inherit their parent's phenotype) numbers of all individuals are always underestimated. We conclude that by using a phenotypic gambit approach evolutionary dynamics can be incorporated into individual based models, and that all that is required is an understanding of the probability of offspring inheriting the parental phenotype

Visualization of Genomic Changes by Segmented Smoothing Using an L0 Penalty

Copy number variations (CNV) and allelic imbalance in tumor tissue can show strong segmentation. Their graphical presentation can be enhanced by appropriate smoothing. Existing signal and scatterplot smoothers do not respect segmentation well. We present novel algorithms that use a penalty on the norm of differences of neighboring values. Visualization is our main goal, but we compare classification performance to that of VEGA