Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userAn ensemble approach to the study of the emergence of metabolic and proliferative disorders via Flux Balance Analysis
109
0
0.0
(
0
)
Authors
Chiara Damiani
Ask ChatGPT about the research
No Arabic abstract
An extensive rewiring of cell metabolism supports enhanced proliferation in cancer cells. We propose a systems level approach to describe this phenomenon based on Flux Balance Analysis (FBA). The approach does not explicit a cell biomass formation reaction to be maximized, but takes into account an ensemble of alternative flux distributions that match the cancer metabolic rewiring (CMR) phenotype description. The underlying concept is that the analysis the common/distinguishing properties of the ensemble can provide indications on how CMR is achieved and sustained and thus on how it can be controlled.
rate research
Read More
Systems Biology is a fundamental field and paradigm that introduces a new era in Biology. The crux of its functionality and usefulness relies on metabolic networks that model the reactions occurring inside an organism and provide the means to understand the underlying mechanisms that govern biological systems. Even more, metabolic networks have a broader impact that ranges from resolution of ecosystems to personalized medicine.The analysis of metabolic networks is a computational geometry oriented field as one of the main operations they depend on is sampling uniformly points from polytopes; the latter provides a representation of the steady states of the metabolic networks. However, the polytopes that result from biological data are of very high dimension (to the order of thousands) and in most, if not all, the cases are considerably skinny. Therefore, to perform uniform random sampling efficiently in this setting, we need a novel algorithmic and computational framework specially tailored for the properties of metabolic networks.We present a complete software framework to handle sampling in metabolic networks. Its backbone is a Multiphase Monte Carlo Sampling (MMCS) algorithm that unifies rounding and sampling in one pass, obtaining both upon termination. It exploits an improved variant of the Billiard Walk that enjoys faster arithmetic complexity per step. We demonstrate the efficiency of our approach by performing extensive experiments on various metabolic networks. Notably, sampling on the most complicated human metabolic network accessible today, Recon3D, corresponding to a polytope of dimension 5 335 took less than 30 hours. To our knowledge, that is out of reach for existing software.
Motivation: Genome-wide association studies (GWASs), which assay more than a million single nucleotide polymorphisms (SNPs) in thousands of individuals, have been widely used to identify genetic risk variants for complex diseases. However, most of the variants that have been identified contribute relatively small increments of risk and only explain a small portion of the genetic variation in complex diseases. This is the so-called missing heritability problem. Evidence has indicated that many complex diseases are genetically related, meaning these diseases share common genetic risk variants. Therefore, exploring the genetic correlations across multiple related studies could be a promising strategy for removing spurious associations and identifying underlying genetic risk variants, and thereby uncovering the mystery of missing heritability in complex diseases. Results: We present a general and robust method to identify genetic patterns from multiple large-scale genomic datasets. We treat the summary statistics as a matrix and demonstrate that genetic patterns will form a low-rank matrix plus a sparse component. Hence, we formulate the problem as a matrix recovering problem, where we aim to discover risk variants shared by multiple diseases/traits and those for each individual disease/trait. We propose a convex formulation for matrix recovery and an efficient algorithm to solve the problem. We demonstrate the advantages of our method using both synthesized datasets and real datasets. The experimental results show that our method can successfully reconstruct both the shared and the individual genetic patterns from summary statistics and achieve better performance compared with alternative methods under a wide range of scenarios.
Metapopulations are models of ecological systems, describing the interactions and the behavior of populations that live in fragmented habitats. In this paper, we present a model of metapopulations based on the multivolume simulation algorithm tau-DPP, a stochastic class of membrane systems, that we utilize to investigate the influence that different habitat topologies can have on the local and global dynamics of metapopulations. In particular, we focus our analysis on the migration rate of individuals among adjacent patches, and on their capability of colonizing the empty patches in the habitat. We compare the simulation results obtained for each habitat topology, and conclude the paper with some proposals for other research issues concerning metapopulations.
In this work we introduce some preliminary analyses on the role of a semi-permeable membrane in the dynamics of a stochastic model of catalytic reaction sets (CRSs) of molecules. The results of the simulations performed on ensembles of randomly generated reaction schemes highlight remarkable differences between this very simple protocell description model and the classical case of the continuous stirred-tank reactor (CSTR). In particular, in the CSTR case, distinct simulations with the same reaction scheme reach the same dynamical equilibrium, whereas, in the protocell case, simulations with identical reaction schemes can reach very different dynamical states, despite starting from the same initial conditions.
Over the last few years, several computational techniques have been devised to recover protein complexes from the protein interaction (PPI) networks of organisms. These techniques model dense subnetworks within PPI networks as complexes. However, our comprehensive evaluations revealed that these techniques fail to reconstruct many gold standard complexes that are sparse in the networks (only 71 recovered out of 123 known yeast complexes embedded in a network of 9704 interactions among 1622 proteins). In this work, we propose a novel index called Component-Edge (CE) score to quantitatively measure the notion of complex derivability from PPI networks. Using this index, we theoretically categorize complexes as sparse or dense with respect to a given network. We then devise an algorithm SPARC that selectively employs functional interactions to improve the CE scores of predicted complexes, and thereby elevates many of the sparse complexes to dense. This empowers existing methods to detect these sparse complexes. We demonstrate that our approach is effective in reconstructing significantly many complexes missed previously (104 recovered out of the 123 known complexes or ~47% improvement).
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
