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Evolving complexity: how tinkering shapes cells, software and ecological networksJul 12 2019A common trait of complex systems is that they can be represented by means of a network of interacting parts. It is, in fact, the network organisation (more than the parts) what largely conditions most higher-level properties, which are not reducible ... More

Theoretical Limit Of Concentration Sensing of Single Receptor Artificial BiosensorsJul 11 2019Artificially engineered biosensors are highly inefficient in accurately measuring the concentration of biomarkers, particularly, during early diagnosis of diseases. On the other hand, single cellular systems such as chemotactic bacteria can sense their ... More

Fundamental Limitations in Biomarker Based Early Disease DiagnosisJul 11 2019Clinical biosensors with low detection limit hold significant promise in the early diagnosis of debilitating diseases. Recent progress in sensor development has led to the demonstration of detection capable of detecting target molecules even down to single-molecule ... More

On Quantitative Comparison of Chemical Reaction Network ModelsJul 09 2019Chemical reaction networks (CRNs) provide a convenient language for modelling a broad variety of biological systems. These models are commonly studied with respect to the time series they generate in deterministic or stochastic simulations. Their dynamic ... More

Quantitative Immunology for PhysicistsJul 08 2019The adaptive immune system is a dynamical, self-organized multiscale system that protects vertebrates from both pathogens and internal irregularities, such as tumours. For these reason it fascinates physicists, yet the multitude of different cells, molecules ... More

Role of Toll-Like Receptors in the interplay between pathogen and damage associated molecular patternsJul 08 2019Various theoretical studies have been carried out to infer relevant protein-protein interactions among pathogens and their hosts. Such studies are generally based on preferential attachment of bacteria / virus to their human receptor homologs. We have ... More

Network analysis of synonymous codon usageJul 07 2019Most amino acids are encoded by multiple synonymous codons. For an amino acid, some of its synonymous codons are used much more rarely than others. Analyses of positions of such rare codons in protein sequences revealed that rare codons can impact co-translational ... More

A multifactorial evaluation framework for gene regulatory network reconstructionJun 28 2019In the past years, many computational methods have been developed to infer the structure of gene regulatory networks from time-series data. However, the applicability and accuracy presumptions of such algorithms remain unclear due to experimental heterogeneity. ... More

On the robust existence of piecewise quadratic Lyapunov functions for hybrid models of gene regulatory networksJun 28 2019In this work we addressed the problem of stability analysis for an uncertain piecewise affine model of a genetic regulatory network. In particular we considered polytopic parameter uncertainties on the proteins production rate functions, giving conditions ... More

Persistence of Excitation for Koopman Operator Represented Dynamical SystemsJun 25 2019The increase in complexity of engineered systems and naturally occurring systems, coupled with increasingly data-driven representations of these systems motivates the need for design of experiment frameworks for nonlinear system identification. In the ... More

Inter-residue, inter-protein and inter-family coevolution: bridging the scalesJun 24 2019Interacting proteins coevolve at multiple but interconnected scales, from the residue-residue over the protein-protein up to the family-family level. The recent accumulation of enormous amounts of sequence data allows for the development of novel, data-driven ... More

Independent channels for miRNA biosynthesis ensure efficient static and dynamic control in the regulation of the early stages of myogenesisJun 24 2019Motivated by recent experimental work, we define and study a deterministic model of the complex miRNA-based regulatory circuit that putatively controls the early stage of myogenesis in human. We aim in particular at a quantitative understanding of (i) ... More

Quantifying Side Effects in Multistate Discrete NetworksJun 22 2019Developing efficient computational methods to change the state of a cell from an undesirable condition, e.g. diseased, into a desirable, e.g. healthy, condition is an important goal of systems biology. The identification of potential interventions can ... More

A reaction network scheme which implements inference and learning for Hidden Markov ModelsJun 22 2019With a view towards molecular communication systems and molecular multi-agent systems, we propose the Chemical Baum-Welch Algorithm, a novel reaction network scheme that learns parameters for Hidden Markov Models (HMMs). Each reaction in our scheme changes ... More

Control of noise in gene expression by transcriptional reinitiationJun 21 2019Gene expression is a noisy process. That consists of several random events among which the reinitiation of transcription by RNAP is an important one. The binding event of RNAP to the active state of the gene is an probabilistic process and therefore introduces ... More

Universal properties of concentration sensing in large ligand-receptor networksJun 20 2019Cells estimate concentrations of chemical ligands in their environment using a limited set of receptors. Recent work has shown that the temporal sequence of binding and unbinding events on just a single receptor can be used to estimate the concentrations ... More

Endotactic Networks and Toric Differential InclusionsJun 19 2019An important dynamical property of biological interaction networks is persistence, which intuitively means that "no species goes extinct". It has been conjectured that dynamical system models of weakly reversible networks (i.e., networks for which each ... More

Hunchback promoters can readout morphogenetic positional information in less than a minuteJun 19 2019Jun 21 2019The first cell fate decisions in the developing fly embryo are made very rapidly : hunchback genes decide in a few minutes whether a given nucleus follows the anterior or the posterior developmental blueprint by reading out the positional information ... More

Hunchback promoters can readout morphogenetic positional information in less than a minuteJun 19 2019The first cell fate decisions in the developing fly embryo are made very rapidly : hunchback genes decide in a few minutes whether a given nucleus follows the anterior or the posterior developmental blueprint by reading out the positional information ... More

rna2rna: Predicting lncRNA-microRNA-mRNA Interactions from Sequence with Integration of Interactome and Biological Annotation DataJun 17 2019Long non-coding RNA, microRNA, and messenger RNA enable key regulations of various biological processes through a variety of diverse interaction mechanisms. Identifying the interactions and cross-talk between these heterogeneous RNA classes is essential ... More

Conditional Monte Carlo for Reaction NetworksJun 12 2019Reaction networks are often used to model interacting species in fields such as biochemistry and ecology. When the counts of the species are sufficiently large, the dynamics of their concentrations are typically modeled via a system of differential equations. ... More

Steady State Invariants and Multistationarity for Families of Toric Reaction NetworksJun 10 2019We study families of chemical reaction networks, with toric steady states. Larger family members are constructed algorithmically from a smallest network and we show that many results about the entire family can be obtained by studying the small family ... More

Dynamic metabolic resource allocation based on the maximum entropy principleJun 10 2019Jun 24 2019This paper introduces a dynamic metabolic modelling framework that is a synthesis of recent ideas on resource allocation and the powerful optimal control formulation of Ramkrishna and colleagues. In particular, their work is extended based on the hypothesis ... More

Dynamic metabolic resource allocation based on the maximum entropy principleJun 10 2019This paper introduces a dynamic metabolic modelling framework that is a synthesis of recent ideas on resource allocation and the powerful optimal control formulation of Ramkrishna and colleagues. In particular, their work is extended based on the hypothesis ... More

Wasserstein Weisfeiler-Lehman Graph KernelsJun 04 2019Graph kernels are an instance of the class of $\mathcal{R}$-Convolution kernels, which measure the similarity of objects by comparing their substructures. Despite their empirical success, most graph kernels use a naive aggregation of the final set of ... More

Optimal reporter placement in sparsely measured genetic networks using the Koopman operatorJun 03 2019Optimal sensor placement is an important yet unsolved problem in control theory. In this paper, we make use of the Koopman observability gramian to develop an algorithm for optimal sensor placement of discrete time autonomous nonlinear dynamical systems. ... More

Concurrency in Boolean networksMay 31 2019Boolean networks (BNs) are widely used to model the qualitative dynamics of biological systems. Besides the logical rules determining the evolution of each component with respect to the state of its regulators, the scheduling of component updates can ... More

MolecularRNN: Generating realistic molecular graphs with optimized propertiesMay 31 2019Designing new molecules with a set of predefined properties is a core problem in modern drug discovery and development. There is a growing need for de-novo design methods that would address this problem. We present MolecularRNN, the graph recurrent generative ... More

Physically-Plausible Modelling of Biomolecular Systems: A Simplified, Energy-Based Model of the Mitochondrial Electron Transport ChainMay 30 2019Systems biology and whole-cell modelling are demanding increasingly comprehensive mathematical models of cellular biochemistry. These models require the development of simplified models of specific processes which capture essential biophysical features ... More

Error-speed correlations in biopolymer synthesisMay 30 2019Synthesis of biopolymers such as DNA, RNA, and proteins are biophysical processes aided by enzymes. Performance of these enzymes is usually characterized in terms of their average error rate and speed. However, because of thermal fluctuations in these ... More

Cooperativity transitions driven by higher-order oligomer formations in ligand-induced receptor dimerizationMay 27 2019While cooperativity in ligand-induced receptor dimerization (e.g., EGF receptors) have been linked with receptor-receptor couplings via state-vector representations of physical observables, effects arising from higher-order oligomer formations of unobserved ... More

Stochastic modeling of gene expression: application of ensembles of trajectoriesMay 25 2019It is well established that gene expression can be modeled as a Markovian stochastic process and hence proper observables might be subjected to large fluctuations and rare events. Since dynamics is often more than statics, one can work with ensembles ... More

Semi-Quantitative Abstraction and Analysis of Chemical Reaction NetworksMay 23 2019Analysis of large continuous-time stochastic systems is a computationally intensive task. In this work we focus on population models arising from chemical reaction networks (CRNs), which play a fundamental role in analysis and design of biochemical systems. ... More

Tikhonov-Fenichel reduction for parameterized critical manifolds with applications to chemical reaction networksMay 20 2019We derive a reduction formula for singularly perturbed ordinary differential equations (in the sense of Tikhonov and Fenichel) with a known parameterization of the critical manifold. No a priori assumptions concerning separation of slow and fast variables ... More

On the existence of Hopf bifurcations in the sequential and distributive double phosphorylation cycleMay 20 2019Protein phosphorylation cycles are important mechanisms of the post translational modification of a protein and as such an integral part of intracellular signaling and control. We consider the sequential phosphorylation and dephosphorylation of a protein ... More

Universal thermodynamic bounds on nonequilibrium response with biochemical applicationsMay 17 2019One of the basic characteristics of any physical system is its response to small perturbations. For instance, response is used to quantify material properties--such as conductivity and viscoelasticity--the sensing capability of cells, and the accuracy ... More

An interdisciplinary survey of network similarity methodsMay 15 2019Comparative graph and network analysis play an important role in both systems biology and pattern recognition, but existing surveys on the topic have historically ignored or underserved one or the other of these fields. We present an integrative introduction ... More

The Energetics of Molecular Adaptation in Transcriptional RegulationMay 15 2019Mutation is a critical mechanism by which evolution explores the functional landscape of proteins. Despite our ability to experimentally inflict mutations at will, it remains difficult to link sequence-level perturbations to systems-level responses. Here, ... More

Tunability of the Dual Feedback Genetic Oscillator Modeled by the Asymmetry in Transcription and TranslationMay 15 2019Oscillatory gene circuits are ubiquitous to biology and are involved in fundamental processes of cell cycle, circadian rhythms and developmental systems. The synthesis of small, non-natural oscillatory genetic circuits have been increasingly used to test ... More

Principles of Information Storage in Small-Molecule MixturesMay 06 2019Molecular data systems have the potential to store information at dramatically higher density than existing electronic media. Some of the first experimental demonstrations of this idea have used DNA, but nature also uses a wide diversity of smaller non-polymeric ... More

Mathematical Models of Gene ExpressionMay 06 2019In this paper we give an overview on the equilibrium properties of a large class of stochastic processes describing the fundamental biological process within cells, {\em the production process of proteins}. Stochastic models classically used in this context ... More

Mathematical Models of Gene ExpressionMay 06 2019May 13 2019In this paper we analyze the equilibrium properties of a large class of stochastic processes describing the fundamental biological process within bacterial cells, {\em the production process of proteins}. Stochastic models classically used in this context ... More

Moment-based analysis of biochemical feedback circuits in a population of chemically interacting cellsMay 06 2019Cells utilize chemical communication to exchange information and coordinate their behavior in noisy environments. Depending on the scenario, communication can reduce variability and shape a collective response, or amplify variability to generate distinct ... More

Control Variates for Stochastic Simulation of Chemical Reaction NetworksMay 02 2019Jun 12 2019Stochastic simulation is a widely used method for estimating quantities in models of chemical reaction networks where uncertainty plays a crucial role. However, reducing the statistical uncertainty of the corresponding estimators requires the generation ... More

Control Variates for Stochastic Simulation of Chemical Reaction NetworksMay 02 2019Stochastic simulation is a widely used method for estimating quantities in models of chemical reaction networks where uncertainty plays a crucial role. However, reducing the statistical uncertainty of the corresponding estimators requires the generation ... More

Optimizing enzymatic catalysts for rapid turnover of substrates with low enzyme sequestrationMay 02 2019We analyse the mechanism of enzyme-substrate catalysis from the perspective of minimizing the load on the enzymes through sequestration, whilst maintaining at least a minimum reaction flux. In particular, we ask: which binding free energies of the enzyme-substrate ... More

Effective computational methods for hybrid stochastic gene networksMay 01 2019At the scale of the individual cell, protein production is a stochastic process with multiple time scales, combining quick and slow random steps with discontinuous and smooth variation. Hybrid stochastic processes, in particular piecewise-deterministic ... More

Parameter regions that give rise to 2[n/2]+1 positive steady states in the n-site phosphorylation systemApr 26 2019The distributive sequential n-site phosphorylation/dephosphorylation system is an important building block in networks of chemical reactions arising in molecular biology, which has been intensively studied. In the nice paper of Wang and Sontag (2008) ... More

Time-dependent product-form Poisson distributions for reaction networks with higher order complexesApr 25 2019It is well known that stochastically modeled reaction networks that are complex balanced admit a stationary distribution that is a product of Poisson distributions. In this paper, we consider the following related question: supposing that the initial ... More

Stochastically modeled weakly reversible reaction networks with a single linkage classApr 18 2019It has been known for nearly a decade that deterministically modeled reaction networks that are weakly reversible and consist of a single linkage class have bounded, persistent trajectories (i.e., for each trajectory $x(t)\in \R^d_{\ge 0}$, the expression ... More

Exactly solvable model of gene expression in proliferating bacterial cell population with stochastic protein bursts and protein partitioningApr 17 2019Many of the existing stochastic models of gene expression contain the first-order decay reaction term that may describe active protein degradation or dilution. If the model variable is interpreted as the molecule number, and not concentration, the decay ... More

Molecular Diversity and Network Complexity in Growing ProtocellsApr 17 2019A great variety of molecular components is encapsulated in cells. Each of these components is replicated for cell reproduction. To address an essential role of the huge diversity of cellular components, we study a model of protocells that convert resources ... More

Quantifying cancer epithelial-mesenchymal plasticity and its association with stemness and immune responseApr 16 2019Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial-mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively ... More

Disease gene prioritization using network topological analysis from a sequence based human functional linkage networkApr 15 2019Sequencing large number of candidate disease genes which cause diseases in order to identify the relationship between them is an expensive and time-consuming task. To handle these challenges, different computational approaches have been developed. Based ... More

Robust information transmission in noisy biochemical reactionsApr 14 2019The fluctuation of intracellular biochemical reactions (intrinsic noise) reduces the information transmitted from an extracellular input to a cellular response. On the other hand, recent studies demonstrated that the transmitted information hardly decreases ... More

Shedding light on the dark matter of the biomolecular structural universe: Progress in RNA 3D structure predictionApr 13 2019Structured RNA plays many functionally relevant roles in molecular life. Structural information, while required to understand the functional cycles in detail, is challenging to gather. Computational methods promise to complement experimental efforts by ... More

The EntOptLayout Cytoscape plug-in for the efficient visualization of major protein complexes in protein-protein interaction and signalling networksApr 08 2019Motivation: Network visualizations of complex biological datasets usually result in 'hairball' images, which do not discriminate network modules. Results: We present the EntOptLayout Cytoscape plug-in based on a recently developed network representation ... More

A proof of unlimited multistability for phosphorylation cyclesApr 05 2019The multiple futile cycle is a phosphorylation system in which a molecular substrate might be phosphorylated sequentially n times by means of an enzymatic mechanism. The system has been studied mathematically using reaction network theory and ordinary ... More

Path mutual information for a class of biochemical reaction networksApr 03 2019Living cells encode and transmit information in the temporal dynamics of biochemical components. Gaining a detailed understanding of the input-output relationship in biological systems therefore requires quantitative measures that capture the interdependence ... More

Strand displacement: a fundamental mechanism in RNA biology?Mar 28 2019DNA and RNA are generally regarded as central molecules in molecular biology. Recent advancements in the field of DNA/RNA nanotechnology successfully used DNA/RNA as programmable molecules to construct molecular machines and nanostructures with predefined ... More

Interlinked GTPase cascades provide a motif for both robust switches and oscillatorsMar 26 2019Jul 08 2019GTPases regulate a wide range of cellular processes, such as intracellular vesicular transport, signal transduction, and protein translation. These hydrolase enzymes operate as biochemical switches by toggling between an active guanosine triphosphate ... More

GTPase cascades provide a motif for both robust switches and oscillatorsMar 26 2019GTPases regulate a wide range of cellular processes, such as intracellular vesicular transport, signal transduction, and protein translation. These hydrolase enzymes operate as biochemical switches by toggling between an active guanosine triphosphate ... More

Angiotensin II cyclic analogs as tools to investigate AT1R biased signaling mechanismsMar 26 2019G protein coupled receptors (GPCRs) produce pleiotropic effects by their capacity to engage numerous signaling pathways once activated. Functional selectivity (also called biased signaling), where specific compounds can bring GPCRs to adopt conformations ... More

Label-free cell signaling pathway deconvolution of Angiotensin type 1 receptor reveals time-resolved G-protein activity and distinct AngII and AngIII\IV responsesMar 26 2019Angiotensin II (AngII) type 1 receptor (AT1R) is a G protein-coupled receptor known for its role in numerous physiological processes and its implication in many vascular diseases. Its functions are mediated through G protein dependent and independent ... More

Influence of photic perturbations on circadian rhythmsMar 25 2019The circadian clock is the molecular mechanism responsible for the adaptation to daily rhythms in living organisms. Oscillations and fluctuations in environmental conditions regulate the circadian clock through signaling pathways. We study the response ... More

Forest structure in epigenetic landscapesMar 22 2019Morphogenesis is the biological process that causes the emergence and changes of patterns (tissues and organs) in living organisms. It is a robust, self-organising mechanism, governed by Genetic Regulatory Networks (GRN), that hasn't been thoroughly understood. ... More

Scaling methods for accelerating kinetic Monte Carlo simulations of chemical reaction networksMar 20 2019Various kinetic Monte Carlo algorithms become inefficient when some of the population sizes in a system are large, which gives rise to a large number of reaction events per unit time. Here, we present a new acceleration algorithm based on adaptive and ... More

Scaling methods for accelerating kinetic Monte Carlo simulations of chemical reaction networksMar 20 2019May 10 2019Various kinetic Monte Carlo algorithms become inefficient when some of the population sizes in a system are large, which gives rise to a large number of reaction events per unit time. Here, we present a new acceleration algorithm based on adaptive and ... More

The self-tuned sensitivity of circadian clocksMar 17 2019Living organisms need to be sensitive to a changing environment while also ignoring uninformative environmental fluctuations. Here, we show that the circadian clock in \textit{Synechococcus elongatus} can naturally tune its environmental sensitivity, ... More

Molecular Polar Belief Propagation Decoder and Successive Cancellation DecoderMar 16 2019By constructing chemical reaction networks (CRNs), this paper proposes a method of synthesizing polar decoder using belief propagation (BP) algorithm and successive cancellation (SC) algorithm, respectively. Theoretical analysis and simulation results ... More

Comparison of Tumor and Normal Cells Protein-Protein Interaction Network ParametersMar 15 2019In this paper, we compared cancerous and normal cell according to their protein-protein interaction network. Cancer is one of the complicated diseases and experimental investigations have been showed that protein interactions have an important role in ... More

On the multistationarity of chemical reaction networksMar 15 2019We present a new conjecture about a necessary condition that a (bio)chemical network has to satisfy for it to exhibit multistationarity. According to a Theorem of Feliu and Wiuf [27, 12], the conjecture is known for strictly monotonic kinetics. We give ... More

Exploiting product molecule number to consider reaction rate fluctuation in elementary reactionsMar 15 2019Mar 18 2019In many chemical reactions, reaction rate fluctuation is inevitable. Reaction rates are different whenever chemical reaction occurs due to their dependence on the number of reaction events or the product number. As such, understanding the impact of rate ... More

Product number counting statistics from stochastic bursting birth-death processesMar 15 2019Mar 21 2019Bursting and non-renewal processes are common phenomena in birth-death process, yet no theory can quantitatively describe a non-renewal birth process with bursting. Here, we present a theoretical model that yields the product number counting statistics ... More

Network Medicine in the age of biomedical big dataMar 13 2019Network medicine is an emerging area of research dealing with molecular and genetic interactions, network biomarkers of disease, and therapeutic target discovery. Large-scale biomedical data generation offers a unique opportunity to assess the effect ... More

Stochastic resonances in a distributed genetic broadcasting system: the NF\k{appa}B/I\k{appa}B paradigmMar 08 2019Gene regulatory networks must relay information from extracellular signals to downstream genes in an efficient, timely and coherent manner. Many complex functional tasks such as the immune response require system-wide broadcasting of information not to ... More

Oscillations and bistability in a model of ERK regulationMar 06 2019This work concerns the question of how two important dynamical properties, oscillations and bistability, emerge in an important biological signaling network. Specifically, we consider a model for dual-site phosphorylation and dephosphorylation of extracellular ... More

Multiscale Dynamics of an Adaptive Catalytic NetworkFeb 28 2019We study the multiscale structure of the Jain-Krishna adaptive network model. This model describes the co-evolution of a set of continuous-time autocatalytic ordinary differential equations and its underlying discrete-time graph structure. The graph dynamics ... More

A Multilayer Structure Facilitates the Production of Antifragile Systems in Boolean Network ModelsFeb 28 2019Antifragility is a property to not only resist stress and but also to benefit from it. Even though antifragile dynamics are found in various real-world complex systems where multiple subsystems interact with each other, the attribute has not been quantitatively ... More

A physical mechanism of heterogeneity in stem cell, cancer and cancer stem cellFeb 27 2019Heterogeneity is ubiquitous in stem cells (SC), cancer cells (CS), and cancer stem cells (CSC). SC and CSC heterogeneity is manifested as diverse sub-populations with self-renewing and unique regeneration capacity. Moreover, the CSC progeny possesses ... More

Network-based methods for disease-gene predictionFeb 26 2019We predict disease-genes relations on the Human Interactome network using a methodology that jointly learns functional and connectivity patterns surrounding proteins. Contrary to other data structures, the Interactome is characterized by high incompleteness ... More

Moment Closure Stability Analysis of Stochastic Reaction Networks with Oscillatory DynamicsFeb 25 2019Biochemical reactions with oscillatory behavior play an essential role in synthetic biology at the microscopic scale. Although a robust stability theory for deterministic chemical oscillators in the macroscopic limit exists, the dynamical stability of ... More

Theory for the optimal detection of time-varying signals in cellular sensing systemsFeb 25 2019Living cells often need to measure chemical concentrations that vary in time. To this end, they deploy many resources, e.g. receptors, downstream signaling molecules, time and energy. Here, we present a theory for the optimal design of a large class of ... More

Rapid Circadian Entrainment in Models of Clock Gene TranscriptionFeb 25 2019Circadian rhythm is usually represented by the 24-hour biological cycles which are mainly driven by the daily light-dark cycle on earth. Light stimulus is widely used as the control input of the circadian system entrainment. In this paper, we study the ... More

Rapid Circadian Entrainment in Models of Circadian Genes RegulationFeb 25 2019Mar 09 2019The light-based minimum-time circadian entrainment problem for mammals, Neurospora, and Drosophila is studied based on the mathematical models of their circadian gene regulation. These models contain high order nonlinear differential equations. Two model ... More

ABM of osteoblast's mechanotransduction pathway: time patterns of critical eventsFeb 23 2019Background: Mechanotransduction in bone cells plays a pivotal role in osteoblast differentiation and bone remodelling. Mechanotransduction provides the link between modulation of the extracellular matrix and intracellular actions. By controlling the balance ... More

A Nonparametric Multi-view Model for Estimating Cell Type-Specific Gene Regulatory NetworksFeb 21 2019We present a Bayesian hierarchical multi-view mixture model termed Symphony that simultaneously learns clusters of cells representing cell types and their underlying gene regulatory networks by integrating data from two views: single-cell gene expression ... More

Robustness of a Biomolecular Oscillator to Pulse PerturbationsFeb 20 2019Biomolecular oscillators can function robustly in the presence of environmental perturbations, which can either be static or dynamic. While the effect of different circuit parameters and mechanisms on the robustness to steady perturbations has been investigated, ... More

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

AligNet: Alignment of Protein-Protein Interaction NetworksFeb 19 2019One of the most difficult problems difficult problem in systems biology is to discover protein-protein interactions as well as their associated functions. The analysis and alignment of protein-protein interaction networks (PPIN), which are the standard ... More

Formation of native shortcut networks and two-state protein foldingFeb 17 2019Mar 19 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

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

Fast consensus clustering in complex networksFeb 11 2019Apr 20 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

Data-driven network alignmentFeb 08 2019Mar 26 2019Biological network alignment (NA) aims to find a node mapping between species' molecular networks that uncovers similar network regions, thus allowing for transfer of functional knowledge between the aligned nodes. However, current NA methods do not end ... 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