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The Essential Role of Thermodynamics in metabolic network modeling: physical insights and computational challengesFeb 19 2019Quantitative studies of cell metabolism are often based on large chemical reaction network models. A steady state approach is suited to analyze phenomena on the timescale of cell growth and circumvents the problem of incomplete experimental knowledge ... More

Formation of native shortcut networks and two-state protein foldingFeb 17 2019A dynamic network-centric approach to study two-state folding from native structure called network dynamics (ND) is introduced. ND applies two fundamental principles of protein folding: hydrophobicity and loop-entropy, on a protein's native residue network ... More

Evaluating Pruning Methods in Gene Network InferenceFeb 16 2019One challenge in gene network inference is distinguishing between direct and indirect regulation. Some algorithms, including ARACNE and Phixer, approach this problem by using pruning methods to eliminate redundant edges in an attempt to explain the observed ... More

Ordered Hexagonal Patterns via Notch-Delta SignalingFeb 13 2019Many developmental processes in biology utilize Notch-Delta signaling to construct an ordered pattern of cellular differentiation. This signaling modality is based on nearest-neighbor contact, as opposed to the more familiar mechanism driven by the release ... More

Fast consensus clustering in complex networksFeb 11 2019Algorithms for community detection are usually stochastic, leading to different partitions for different choices of random seeds. Consensus clustering has proven to be an effective technique to derive more stable and accurate partitions than the ones ... More

Data-driven network alignmentFeb 08 2019Network alignment (NA) aims to find a node mapping between compared networks that uncovers regions of high topological similarity, thus allowing for the transfer of functional knowledge between aligned nodes. For example, one can align protein-protein ... More

Intervention Pathway Discovery via Context-Dependent Dynamic Sensitivity AnalysisFeb 08 2019The sensitivity analysis of biological system models can significantly contribute to identifying and explaining influences of internal or external changes on model and its elements. We propose here a comprehensive framework to study sensitivity of intra-cellular ... More

Biochemical feedback and its application to immune cells II: dynamics and critical slowing downFeb 07 2019Near a bifurcation point, the response time of a system is expected to diverge due to the phenomenon of critical slowing down. We investigate critical slowing down in well-mixed stochastic models of biochemical feedback by exploiting a mapping to the ... More

Ensembles, Dynamics, and Cell Types: Revisiting the Statistical Mechanics Perspective on Cellular RegulationFeb 01 2019Genetic regulatory networks control ontogeny. For fifty years Boolean networks have served as models of such systems, ranging from ensembles of random Boolean networks as models for generic properties of gene regulation to working dynamical models of ... More

From genome to phenome: Predicting multiple cancer phenotypes based on somatic genomic alterations via the genomic impact transformerJan 31 2019Feb 09 2019Motivation: Cancers are mainly caused by somatic genomic alterations (SGAs) that perturb cellular signaling systems and eventually activate oncogenic processes. Therefore, understanding the functional impact of SGAs is a fundamental task in cancer biology ... More

Stochastic modelling reveals mechanisms of metabolic heterogeneityJan 29 2019Phenotypic variation is a hallmark of cellular physiology. Metabolic heterogeneity, in particular, underpins single-cell phenomena such as microbial drug tolerance and growth variability. Much research has focussed on transcriptomic and proteomic heterogeneity, ... More

Steroid Receptors and Vertebrate EvolutionJan 28 2019Considering that life on earth evolved about 3.7 billion years ago, vertebrates are young, appearing in the fossil record during the Cambrian explosion about 542 to 515 million years ago. Results from sequence analyses of genomes from bacteria, yeast, ... More

Stochastic modeling of phenotypic switching and chemoresistance in cancer cell populationsJan 24 2019Phenotypic heterogeneity in cancer cells is widely observed and is often linked to drug resistance. In several cases, such heterogeneity in drug sensitivity of tumors is driven by stochastic and reversible acquisition of a drug tolerant phenotype by individual ... More

Partial Order on the set of Boolean Regulatory FunctionsJan 22 2019Logical models have been successfully used to describe regulatory and signaling networks without requiring quantitative data. However, existing data is insufficient to adequately define a unique model, rendering the parametrization of a given model a ... More

Spatial clustering and common regulatory elements correlate with coordinated gene expressionJan 18 2019Many cellular responses to surrounding cues require temporally concerted transcriptional regulation of multiple genes. In prokaryotic cells, a single-input-module motif with one transcription factor regulating multiple target genes can generate coordinated ... More

Shared Causal Paths underlying Alzheimer's dementia and Type 2 DiabetesJan 16 2019Background: Although Alzheimer's disease (AD) is a central nervous system disease and type 2 diabetes mellitus (T2DM) is a metabolic disorder, an increasing number of genetic epidemiological studies show clear link between AD and T2DM. The current approach ... More

An extended model of wine fermentation including aromas and acidsJan 05 2019The art of viticulture and the quest for making wines has a long tradition and it just started recently that mathematicians entered this field with their main contribution of modelling alcoholic fermentation. These models consist of systems of ordinary ... More

Figure 1 Theory Meets Figure 2 Experiments in the Study of Gene ExpressionDec 30 2018It is tempting to believe that we now own the genome. The ability to read and re-write it at will has ushered in a stunning period in the history of science. Nonetheless, there is an Achilles heel exposed by all of the genomic data that has accrued: we ... More

Structural insights into characterizing binding sites in EGFR kinase mutantsDec 27 2018Over the last two decades epidermal growth factor receptor (EGFR) kinase has become an important target to treat non-small cell lung cancer (NSCLC). Currently, three generations of EGFR kinase-targeted small molecule drugs have been FDA approved. They ... More

Biochemical Szilard engines for memory-limited inferenceDec 20 2018By developing and leveraging an explicit molecular realisation of a measurement-and-feedback-powered Szilard engine, we investigate the extraction of work from complex environments by minimal machines with finite capacity for memory and decision-making. ... More

Antifragility of Random Boolean NetworksDec 17 2018Antifragility is a property that enhances the capability of a system in response to external perturbations. Although the concept has been applied in many areas, a practical measure of antifragility has not been developed yet. Here we propose a simply ... More

α7 nicotinic acetylcholine receptor signaling modulates ovine fetal brain astrocytes transcriptome in response to endotoxin: comparison to microglia, implications for prenatal stress and development of autism spectrum disorderDec 17 2018Dec 31 2018Neuroinflammation in utero may result in lifelong neurological disabilities. Astrocytes play a pivotal role, but the mechanisms are poorly understood. No early postnatal treatment strategies exist to enhance neuroprotective potential of astrocytes. We ... More

Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rateDec 13 2018Cell growth is determined by substrate availability and the cell's metabolic capacity to assimilate substrates into building blocks. Metabolic genes that determine growth rate may interact synergistically or antagonistically, and can accelerate or slow ... More

A finite state projection method for steady-state sensitivity analysis of stochastic reaction networksDec 11 2018Consider the standard stochastic reaction network model where the dynamics is given by a continuous-time Markov chain over a discrete lattice. For such models, estimation of parameter sensitivities is an important problem, but the existing computational ... More

Origin of Biomolecular NetworksNov 30 2018Biomolecular networks have already found great utility in characterizing complex biological systems arising from pair-wise interactions amongst biomolecules. Here, we review how graph theoretical approaches can be applied not only for a better understanding ... More

Finding Zeros of Hölder Metrically Subregular Mappings via Globally Convergent Levenberg-Marquardt MethodsNov 30 2018Dec 05 2018We present two globally convergent Levenberg-Marquardt methods for finding zeros of H\"{o}lder metrically subregular mappings that may have non-isolated zeros. The first method unifies the Levenberg- Marquardt direction and an Armijo-type line search, ... More

Identifiability from some variablesNov 20 2018Under mass-action kinetics, biochemical reaction networks give rise to polynomial autonomous dynamical systems whose parameters are often difficult to estimate. We deal in this paper with the problem of identifying the kinetic parameters of a class of ... More

A Faster DiSH: Hardware Implementation of a Discrete Cell Signaling Network SimulatorNov 19 2018Development of fast methods to conduct in silico experiments using computational models of cellular signaling is a promising approach toward advances in personalized medicine. However, software-based cellular network simulation has run-times plagued by ... More

PaccMann: Prediction of anticancer compound sensitivity with multi-modal attention-based neural networksNov 16 2018We present a novel approach for the prediction of anticancer compound sensitivity by means of multi-modal attention-based neural networks (PaccMann). In our approach, we integrate three key pillars of drug sensitivity, namely, the molecular structure ... More

Towards control of cellular decision-making networks in the epithelial-to-mesenchymal transitionNov 15 2018Jan 18 2019We present the epithelial-to-mesenchymal transition (EMT) from two perspectives: experimental/technological and theoretical. We review the state of the current understanding of the regulatory networks that underlie EMT in three physiological contexts: ... More

Controllability, Multiplexing, and Transfer Learning in Networks using Evolutionary LearningNov 14 2018Networks are fundamental building blocks for representing data, and computations. Remarkable progress in learning in structurally defined (shallow or deep) networks has recently been achieved. Here we introduce evolutionary exploratory search and learning ... More

The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant gliomaNov 09 2018The lncRNA HOTAIR has been implicated in several human cancers. Here, we evaluated the molecular alterations and upstream regulatory mechanisms of HOTAIR in glioma, the most common primary brain tumors, and its clinical relevance. HOTAIR gene expression, ... More

Coloured Noise from Stochastic Inflows in Reaction-Diffusion SystemsOct 30 2018Nov 30 2018In this paper we present a framework for investigating coloured noise in reaction-diffusion systems. We start by considering a deterministic reaction-diffusion equation and show how external forcing can cause temporally correlated or coloured noise. Here, ... More

Inherent stochasticity precludes hysteresis in gene regulatory networksOct 24 2018Dec 18 2018Cell fate determination, the process through which cells commit to differentiated states, has been shown to be mediated by gene regulatory motifs with mutually exclusive expression states. The classical picture for deterministic cell decision making includes ... More

The Multi-Scale Impact of the Alzheimer's Disease in the Topology Diversity of Astrocytes Molecular Communications NanonetworksOct 22 2018The Internet of Bio-Nano-Things is a new paradigm that can bring novel remotely controlled actuation and sensing techniques inside the human body. Towards precise bionano sensing techniques in the brain, we investigate the challenges of modelling spatial ... More

Multistationarity in the space of total concentrations for systems that admit a monomial parametrizationOct 18 2018We apply tools from real algebraic geometry to the problem of multistationarity of chemical reaction networks. A particular focus is on the case of reaction networks whose steady states admit a monomial parametrization. For such systems we show that in ... More

Seemingly stable chemical kinetics can be stable, marginally stable, or unstableOct 15 2018We present three examples of chemical reaction networks whose ordinary differential equation scaling limit are almost identical and in all cases stable. Nevertheless, the Markov jump processes associated to these reaction networks display the full range ... More

Translocatome: a novel resource for the analysis of protein translocation between cellular organellesOct 15 2018Jan 15 2019Here we present Translocatome, the first dedicated database of human translocating proteins. The core of the Translocatome database is the manually curated data set of 213 human translocating proteins listing the source of their experimental validation, ... More

Context in Synthetic Biology: Memory Effects of Environments with Mono-molecular ReactionsSep 25 2018Jan 11 2019Synthetic biology aims at designing modular genetic circuits that can be assembled according to the desired function. When embedded in a cell, a circuit module becomes a small subnetwork within a larger environmental network, and its dynamics is therefore ... More

Seeing the wood for the trees: a forest of methods for optimisation and omic-network integration in metabolic modellingSep 21 2018Metabolic modelling has entered a mature phase with dozens of methods and software implementations available to the practitioner and the theoretician. It is not easy for a modeller to be able to see the wood (or the forest) for the trees. Driven by this ... More

Discrepancies between extinction events and boundary equilibria in reaction networksSep 12 2018Reaction networks are mathematical models of interacting chemical species that are primarily used in biochemistry. There are two modeling regimes that are typically used, one of which is deterministic and one that is stochastic. In particular, the deterministic ... More

Emergence of oscillations in a mixed-mechanism phosphorylation systemSep 08 2018Feb 01 2019This work investigates the emergence of oscillations in one of the simplest cellular signaling networks exhibiting oscillations, namely, the dual-site phosphorylation and dephosphorylation network (futile cycle), in which the mechanism for phosphorylation ... More

Tier structure of strongly endotactic reaction networksAug 16 2018Reaction networks are mainly used to model the time-evolution of molecules of interacting chemical species. Stochastic models are typically used when the counts of the molecules are low, whereas deterministic models are used when the counts are in high ... More

Revisiting a synthetic intracellular regulatory network that exhibits oscillationsAug 01 2018Dec 31 2018In 2000, Elowitz and Leibler introduced the repressilator--a synthetic gene circuit with three genes that cyclically repress transcription of the next gene--as well as a corresponding mathematical model. Experimental data and model simulations exhibited ... More

Profiling of FSHR Negative Allosteric Modulators on LH/CGR Reveals Biased Antagonism with Implications in SteroidogenesisAug 01 2018Biased signaling has recently emerged as an interesting mean to modulate the function of many G protein-coupled receptors (GPCRs). Previous studies reported two negative allosteric modulators (NAMs) of follicle-stimulating hormone receptor (FSHR), ADX68692 ... More

Advances in computational modeling approaches in pituitary gonadotropin signalingAug 01 2018Pituitary gonadotropins play an essential and pivotal role in the control of human and animal reproduction within the hypothalamic-pituitary-gonadal (HPG) axis. The computational modeling of pituitary gonadotropin signaling encompasses phenomena of different ... More

Antagonistic Phenomena in Network DynamicsAug 01 2018Recent research on the network modeling of complex systems has led to a convenient representation of numerous natural, social, and engineered systems that are now recognized as networks of interacting parts. Such systems can exhibit a wealth of phenomena ... More

Workflow description to dynamically model β-arrestin signaling networksJul 31 2018Dynamic models of signaling networks allow the formulation of hypotheses on the topology and kinetic rate laws characterizing a given molecular network, in-depth exploration and confrontation with kinetic biological data. Despite its standardization, ... More

Follicle-stimulating hormone receptor: Advances and remaining challengesJul 31 2018Follicle-stimulating hormone (FSH) is produced in the pituitary and is essential for reproduction. It specifically binds to a membrane receptor (FSHR) expressed in somatic cells of the gonads. The FSH/FSHR system presents many peculiarities compared to ... More

Human Luteinizing Hormone and Chorionic Gonadotropin Display Biased Agonism at the LH and LH/CG ReceptorsJul 31 2018Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) have been considered biologically equivalent because of their structural similarities and their binding to the same receptor; the LH/CGR. However, accumulating evidence suggest that LH/CGR ... More

Computational modeling approaches in gonadotropin signalingJul 31 2018Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play essential roles in animal reproduction. They exert their function through binding to their cognate receptors, which belong to the large family of G protein-coupled receptors (GPCRs). ... More

On the scale-free nature of RNA secondary structure networksJun 30 2018A network is scale-free if its connectivity density function is proportional to a power-law distribution. Scale-free networks may provide an explanation for the robustness observed in certain physical and biological phenomena, since the presence of a ... More

Nonnegative linear elimination for chemical reaction networksJun 29 2018We consider linear elimination of variables in steady state equations of a chemical reaction network. Particular subsets of variables corresponding to sets of so-called reactant-noninteracting species, are introduced. The steady state equations for the ... More

Biochemical Coupling Through Emergent Conservation LawsJun 28 2018Bazhin has analyzed ATP coupling in terms of quasiequilibrium states where fast reactions have reached an approximate steady state while slow reactions have not yet reached equilibrium. After an expository introduction to the relevant aspects of reaction ... More

Sequential Experimental Design for Optimal Structural Intervention in Gene Regulatory Networks Based on the Mean Objective Cost of UncertaintyMay 30 2018Scientists are attempting to use models of ever increasing complexity, especially in medicine, where gene-based diseases such as cancer require better modeling of cell regulation. Complex models suffer from uncertainty and experiments are needed to reduce ... More

The combined effects of Feller diffusion and transcriptional/translational bursting in simple gene networksMay 30 2018Jul 18 2018We study a stochastic model of biosynthesis of proteins in generic bacterial operons. The stochasticity arises from two different processes, namely from `bursting' production of either mRNA and/or protein (in the transcription/translation process) and ... More

Network Enhancement: a general method to denoise weighted biological networksMay 09 2018Jun 01 2018Networks are ubiquitous in biology where they encode connectivity patterns at all scales of organization, from molecular to the biome. However, biological networks are noisy due to the limitations of measurement technology and inherent natural variation, ... More

FASK with Interventional Knowledge Recovers Edges from the Sachs ModelMay 06 2018We report a procedure that, in one step from continuous data with minimal preparation, recovers the graph found by Sachs et al. \cite{sachs2005causal}, with only a few edges different. The algorithm, Fast Adjacency Skewness (FASK), relies on a mixture ... More

Mechanism Deduction from Noisy Chemical Reaction NetworksMar 25 2018Dec 19 2018We introduce KiNetX, a fully automated meta-algorithm for the kinetic analysis of complex chemical reaction networks derived from semi-accurate but efficient electronic structure calculations. It is designed to (i) accelerate the automated exploration ... More

Analysis of Triplet Motifs in Biological Signed Oriented Graphs Suggests a Relationship Between Fine Topology and FunctionMar 17 2018Mar 20 2018Background: Networks in different domains are characterized by similar global characteristics while differing in local structures. To further extend this concept, we investigated network regularities on a fine scale in order to examine the functional ... More

The hypotensive effect of activated apelin receptor is correlated with \b{eta}-arrestin recruitmentMar 12 2018Mar 14 2018The apelinergic system is an important player in the regulation of both vascular tone and cardiovascular function, making this physiological system an attractive target for drug development for hypertension, heart failure and ischemic heart disease. Indeed, ... More

The signaling signature of the neurotensin type 1 receptor with endogenous ligandsMar 12 2018Mar 14 2018The human neurotensin 1 receptor (hNTS1) is a G protein-coupled receptor involved in many physiological functions, including analgesia, hypothermia, and hypotension. To gain a better understanding of which signaling pathways or combination of pathways ... More

CANA: A python package for quantifying control and canalization in Boolean NetworksMar 09 2018May 09 2018Logical models offer a simple but powerful means to understand the complex dynamics of biochemical regulation, without the need to estimate kinetic parameters. However, even simple automata components can lead to collective dynamics that are computationally ... More

Tensorial and bipartite block models for link prediction in layered networks and temporal networksMar 05 2018Many real-world complex systems are well represented as multilayer networks; predicting interactions in those systems is one of the most pressing problems in predictive network science. To address this challenge, we introduce two stochastic block models ... More

Algorithmic Complexity and Reprogrammability of Chemical Structure NetworksFeb 16 2018Mar 18 2018Here we address the challenge of profiling causal properties and tracking the transformation of chemical compounds from an algorithmic perspective. We explore the potential of applying a computational interventional calculus based on the principles of ... More

Molecular Computing for Markov ChainsFeb 14 2018In this paper, it is presented a methodology for implementing arbitrarily constructed time-homogenous Markov chains with biochemical systems. Not only discrete but also continuous-time Markov chains are allowed to be computed. By employing chemical reaction ... More

Molecular Regulation of Histamine SynthesisFeb 07 2018Histamine is a critical mediator of IgE/ cell-mediated anaphylaxis, a neurotransmitter and a regulator of gastric acid secretion. Histamine is a monoamine synthesized from the amino acid histidine through a reaction catalyzed by the enzyme histidine decarboxylase ... More

Comparing multiple networks using the Co-expression Differential Network Analysis (CoDiNA)Feb 02 2018Sep 28 2018Biomedical sciences are increasingly recognising the relevance of gene co-expression-networks for analysing complex-systems, phenotypes or diseases. When the goal is investigating complex-phenotypes under varying conditions, it comes naturally to employ ... More

$S$-Leaping: An adaptive, accelerated stochastic simulation algorithm, bridging $τ$-leaping and $R$-leapingFeb 01 2018Jun 29 2018We propose the $S$-leaping algorithm for the acceleration of Gillespie's stochastic simulation algorithm that combines the advantages of the two main accelerated methods; the $\tau$-leaping and $R$-leaping algorithms. These algorithms are known to be ... More

Generalizing Gillespie's direct method to enable network-free simulationsJan 30 2018Gillespie's direct method for stochastic simulation of chemical kinetics is a staple of computational systems biology research. However, the algorithm requires explicit enumeration of all reactions and all chemical species that may arise in the system. ... More

The exit time finite state projection scheme: bounding exit distributions and occupation measures of continuous-time Markov chainsJan 29 2018Jan 25 2019We introduce the exit time finite state projection (ETFSP) scheme, a truncation-based method that yields approximations to the exit distribution and occupation measure associated with the time of exit from a domain (i.e., the time of first passage to ... More

Inter-cellular Interactions and Patterns: Vertebrate Development and Embryonic Stem CellsJan 27 2018Development from egg to embryo to adult is a fascinating instance of biological self-organization for which genetics has supplied us with a parts list. It remains to find the principles organizing the assembly of those parts. In the last decade embryonic ... More

The Stretch to Stray on Time: Resonant Length of Random Walks in a TransientJan 16 2018First-passage times in random walks have a vast number of diverse applications in physics, chemistry, biology, and finance. In general, environmental conditions for a stochastic process are not constant on the time scale of the average first-passage time, ... More

Predictive Systems ToxicologyJan 15 2018In this review we address to what extent computational techniques can augment our ability to predict toxicity. The first section provides a brief history of empirical observations on toxicity dating back to the dawn of Sumerian civilization. Interestingly, ... More

Gene regulatory network inference: an introductory surveyJan 12 2018Gene regulatory networks are powerful abstractions of biological systems. Since the advent of high-throughput measurement technologies in biology in the late 90s, reconstructing the structure of such networks has been a central computational problem in ... More

Scale-free networks are rareJan 09 2018A central claim in modern network science is that real-world networks are typically "scale free," meaning that the fraction of nodes with degree $k$ follows a power law, decaying like $k^{-\alpha}$, often with $2 < \alpha < 3$. However, empirical evidence ... More

A comprehensive statistical study of metabolic and protein-protein interaction network propertiesDec 20 2017Understanding the mathematical properties of graphs underling biological systems could give hints on the evolutionary mechanisms behind these structures. In this article we perform a complete statistical analysis over thousands of graphs representing ... More

Gene regulatory and signalling networks exhibit distinct topological distributions of motifsDec 19 2017Apr 12 2018The biological processes of cellular decision making and differentiation involve a plethora of signalling pathways and gene regulatory circuits. These networks, in their turn, exhibit a multitude of motifs playing crucial parts in regulating network activity. ... More

Node Balanced Steady States: Unifying and Generalizing Complex and Detailed Balanced Steady StatesNov 19 2017We introduce a unifying and generalizing framework for complex and detailed balanced steady states in chemical reaction network theory. To this end, we generalize the graph commonly used to represent a reaction network. Specifically, we introduce a graph, ... More

A Sequence-Based Mesh Classifier for the Prediction of Protein-Protein InteractionsNov 12 2017The worldwide surge of multiresistant microbial strains has propelled the search for alternative treatment options. The study of Protein-Protein Interactions (PPIs) has been a cornerstone in the clarification of complex physiological and pathogenic processes, ... More

On the geometry of chemical reaction networks: Lyapunov function and large deviationsOct 19 2017Apr 17 2018In an earlier paper, we proved the validity of large deviations theory for the particle approximation of quite general chemical reaction networks (CRNs). In this paper, we extend its scope and present a more geometric insight into the mechanism of that ... More

Graphically balanced equilibria and stationary measures of reaction networksOct 16 2017May 17 2018The graph-related symmetries of a reaction network give rise to certain special equilibria (such as complex balanced equilibria) in deterministic models of dynamics of the reaction network. Correspondingly, in the stochastic setting, when modeled as a ... More

Analysis of biochemical mechanisms provoking differential spatial expression in Hh target genesSep 28 2017This work analyses the transcriptional effects of some biochemical mechanisms proposed in previous literature which attempts to explain the differential spatial expression of Hedgehog target genes involved in Drosophila development. Specifically, the ... More

Large scale evaluation of differences between network-based and pairwise sequence-alignment-based methods of dendrogram reconstructionSep 26 2017Dendrograms are a way to represent evolutionary relationships between organisms. Nowadays, these are inferred based on the comparison of genes or protein sequences by taking into account their differences and similarities. The genetic material of choice ... More

Blood-based metabolic signatures in Alzheimer's diseaseSep 21 2017Introduction: Identification of blood-based metabolic changes might provide early and easy-to-obtain biomarkers. Methods: We included 127 AD patients and 121 controls with CSF-biomarker-confirmed diagnosis (cut-off tau/A$\beta_{42}$: 0.52). Mass spectrometry ... More

Complexity of Model Testing for Dynamical Systems with Toric Steady StatesJul 24 2017Dec 14 2018In this paper we investigate the complexity of model selection and model testing for dynamical systems with toric steady states. Such systems frequently arise in the study of chemical reaction networks. We do this by formulating these tasks as a constrained ... More

Biological implications of $\mathfrak{so}(2,1)$ symmetry in exact solutions for a self-repressing geneJul 14 2017We chemically characterize the symmetries underlying the exact solutions of a stochastic negatively self-regulating gene. The breaking of symmetry at low molecular number causes three effects. Average protein number differs from the deterministically ... More

Flows, scaling, and the control of moment hierarchies for stochastic chemical reaction networksJun 23 2017Stochastic chemical reaction networks (CRNs) are complex systems which combine the features of concurrent transformation of multiple variables in each elementary reaction event, and nonlinear relations between states and their rates of change. Most general ... More

Methods to Expand Cell Signaling Models using Automated Reading and Model CheckingJun 15 2017Biomedical research results are being published at a high rate, and with existing search engines, the vast amount of published work is usually easily accessible. However, reproducing published results, either experimental data or observations is often ... More

HiDi: An efficient reverse engineering schema for large scale dynamic regulatory network reconstruction using adaptive differentiationJun 05 2017Jun 08 2017The use of differential equations (ODE) is one of the most promising approaches to network inference. The success of ODE-based approaches has, however, been limited, due to the difficulty in estimating parameters and by their lack of scalability. Here ... More

Dynamics of post-translational modification systems: recent progress and future directionsMay 31 2017Oct 24 2017Post-translational modification (PTM) of proteins plays a key role in signal transduction, and hence significant effort has gone toward understanding how PTM networks process information. This involves, on the theory side, analyzing the dynamical systems ... More

Parallel replica dynamics method for bistable stochastic reaction networks: simulation and sensitivity analysisMay 18 2017Stochastic reaction networks that exhibit bistability are common in many fields such as systems biology and materials science. Sampling of the stationary distribution is crucial for understanding and characterizing the long term dynamics of bistable stochastic ... More

DiSH Simulator: Capturing Dynamics of Cellular Signaling with Heterogeneous KnowledgeMay 07 2017We present DiSH-Sim, a simulator for large discrete models of biological signal transduction pathways, capable of simulating networks with multi-valued elements in both deterministic and stochastic manner. We focus on order of update and thus incorporate ... More

Minimal Controllability of Conjunctive Boolean Networks is NP-CompleteApr 21 2017Given a conjunctive Boolean network (CBN) with $n$ state-variables, we consider the problem of finding a minimal set of state-variables to directly affect with an input so that the resulting conjunctive Boolean control network (CBCN) is controllable. ... More

From homogeneous to heterogeneous network alignment via colored graphletsApr 04 2017Mar 28 2018Network alignment (NA) compares networks with the goal of finding a node mapping that uncovers highly similar (conserved) network regions. Existing NA methods are homogeneous, i.e., they can deal only with networks containing nodes and edges of one type. ... More

Biological timekeeping in the presence of stochasticityMar 28 2017Causal ordering of key events in the cell cycle is essential for proper functioning of an organism. Yet, it remains a mystery how a specific temporal program of events is maintained despite ineluctable stochasticity in the biochemical dynamics which dictate ... More

A circuit-preserving mapping from multilevel to Boolean dynamicsMar 27 2017May 08 2017Many discrete models of biological networks rely exclusively on Boolean variables and many tools and theorems are available for analysis of strictly Boolean models. However, multilevel variables are often required to account for threshold effects, in ... More

Local convergence of Levenberg-Marquardt methods under Hölder metric subregularityMar 21 2017Aug 07 2018We describe and analyse Levenberg-Marquardt methods for solving systems of nonlinear equations. More specifically, we propose an adaptive formula for the Levenberg-Marquardt parameter and analyse the local convergence of the method under H\"{o}lder metric ... More

Statistical mechanics for metabolic networks during steady-state growthMar 06 2017Which properties of metabolic networks can be derived solely from stoichiometric information about the network's constituent reactions? Predictive results have been obtained by Flux Balance Analysis (FBA), by postulating that cells set metabolic fluxes ... More

Control of Gene Regulatory Networks with Noisy Measurements and Uncertain InputsFeb 24 2017This paper is concerned with the problem of stochastic control of gene regulatory networks (GRNs) observed indirectly through noisy measurements and with uncertainty in the intervention inputs. The partial observability of the gene states and uncertainty ... More