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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
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
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
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 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
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
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
The Dynamics of Canalizing Boolean NetworksJan 31 2019Boolean networks are a popular modeling framework in computational biology to capture the dynamics of molecular networks, such as gene regulatory networks. It has been observed that many published models of such networks are defined by regulatory rules ... 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
The Thermodynamic Uncertainty Relation in Biochemical OscillationsJan 02 2019Feb 05 2019Living systems regulate many aspects of their behavior through periodic oscillations of molecular concentrations, which function as `biochemical clocks.' These clocks are intrinsically subject to thermal fluctuations, so that the duration of a full oscillation ... 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
Precise spatial scaling in the early fly embryoDec 29 2018The early fly embryo offers a relatively pure version of the problem of spatial scaling in biological pattern formation. Within three hours, a "blueprint" for the final segmented body plan of the animal is visible in striped patterns of gene expression. ... More
Negative differential response in chemical reactionsDec 28 2018Reaction currents in chemical networks usually increase when increasing their driving affinities. But far from equilibrium the opposite can also happen. We find that such negative differential response (NDR) occurs in reaction schemes of major biological ... 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
Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAsDec 22 2018Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended ... 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
Alpha7 nicotinic acetylcholine receptor signaling modulates ovine fetal brain astrocytes transcriptome in response to endotoxinDec 17 2018Apr 09 2019Neuroinflammation 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
Simulation and inference algorithms for stochastic biochemical reaction networks: from basic concepts to state-of-the-artDec 14 2018Jan 30 2019Stochasticity is a key characteristic of intracellular processes such as gene regulation and chemical signalling. Therefore, characterising stochastic effects in biochemical systems is essential to understand the complex dynamics of living things. Mathematical ... 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
Most probable dynamics of a genetic regulatory network under stable Lévy noiseDec 08 2018Numerous studies have demonstrated the important role of noise in the dynamical behaviour of a complex system. The most probable trajectories of nonlinear systems under the influence of Gaussian noise have recently been studied already. However, there ... More
Evolutionary constraints on the complexity of genetic regulatory networks allow predictions of the total number of genetic interactionsDec 04 2018Jan 21 2019Genetic regulatory networks (GRNs) have been widely studied, yet there is a lack of understanding with regards to the final size and properties of these networks, mainly due to no network currently being complete. In this study, we analyzed the distribution ... More
Statistical Model Checking based Analysis of Biological NetworksDec 03 2018We introduce a framework for analyzing ordinary differential equation (ODE) models of biological networks using statistical model checking (SMC). A key aspect of our work is the modeling of single-cell variability by assigning a probability distribution ... More
The minimal model of Hahn for the Calvin cycleDec 03 2018There are many models of the Calvin cycle of photosynthesis in the literature. When investigating the dynamics of these models one strategy is to look at the simplest possible models in order to get the most detailed insights. We investigate a minimal ... 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
Waveforms of molecular oscillations reveal circadian timekeeping mechanismsNov 26 2018Circadian clocks play a pivotal role in orchestrating numerous physiological and developmental events. Waveform shapes of the oscillations of protein abundances can be informative about the underlying biochemical processes of circadian clocks. We derive ... More
Overview of Current Type I/II Kinase InhibitorsNov 23 2018Research on kinase-targeting drugs has made great strides over the last 30 years and is attracting greater attention for the treatment of yet more kinase-related diseases. Currently, 42 kinase drugs have been approved by the FDA, most of which (39) are ... More
Critical slowing down and attractive manifold: a mechanism for dynamic robustness in yeast cell-cycle processNov 23 2018The biological processes that execute complex multiple functions, such as cell cycle, must ensure the order of sequential events and keep the dynamic robustness against various fluctuations. Here, we examine the dynamic mechanism and the fundamental structure ... 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
Networks of ribosome flow models for modeling and analyzing intracellular trafficNov 19 2018The ribosome flow model with input and output (RFMIO) is a deterministic dynamical system that has been used to study the flow of ribosomes during mRNA translation. The RFMIO and its variants encapsulate important properties that are relevant to modeling ... 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
Molecular computersNov 12 2018We propose the chemlambda artificial chemistry, whose behavior strongly suggests that real molecules which embed Interaction Nets patterns and real chemical reactions which resemble Interaction Nets graph rewrites could be a realistic path towards molecular ... More
An annotated list of bivalent chromatin regions in human ES cells: a new tool for cancer epigenetic researchNov 09 2018CpG islands (CGI) marked by bivalent chromatin in stem cells are believed to be more prone to aberrant DNA methylation in tumor cells. The robustness and genome-wide extent of this instructive program in different cancer types remain to be determined. ... More
Imprinting control regions (ICRs) are marked by mono-allelic bivalent chromatin when transcriptionally inactiveNov 09 2018Parental allele-specific expression of imprinted genes is mediated by imprinting control regions (ICRs) that are constitutively marked by DNA methylation imprints on the maternal or paternal allele. Mono-allelic DNA methylation is strictly required for ... 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
Stochastic approximation of high-molecular by bi-molecular reactionsNov 07 2018Biochemical networks, under mass-action kinetics, containing reactions with three or more reactants (called high-molecular reactions) are investigated. An algorithm for stochastically approximating the high-molecular reactions with a set of bi-molecular ... More
Path integral approach to generating functions for multistep post-transcription and post-translation processes and arbitrary initial conditionsOct 30 2018Stochastic fluctuations in the copy number of gene products have perceivable effects on the functioning of gene regulatory networks (GRN). The Master equation (ME) provides a theoretical basis for studying such effects. However, solving the ME can be ... 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
Transient hysteresis and inherent stochasticity in gene regulatory networksOct 24 2018Apr 02 2019Cell fate determination, the process through which cells commit to differentiated states is commonly mediated by gene regulatory motifs with mutually exclusive expression states. The classical deterministic picture for cell fate determination includes ... 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
Discrete Flux and Velocity Fields of Probability and Their Global Maps in Reaction SystemsOct 16 2018Stochasticity plays important roles in reaction systems. Vector fields of probability flux and velocity characterize time-varying and steady-state properties of these systems, including high probability paths, barriers, checkpoints among different stable ... More
Essentiality landscape of metabolic networksOct 16 2018Local perturbations of individual metabolic reactions may result in different levels of lethality, depending on their roles in metabolism and the size of subsequent cascades induced by their failure. Moreover, essentiality of individual metabolic reactions ... 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
Specific low frequency electromagnetic fields induce epigenetic and functional changes in U937 cellsOct 15 2018In this study, we investigated the effects of specific low frequency electromagnetic fields sequences on U937 cells, an in vitro model of human monocyte/macrophage differentiation. U937 cells were exposed to electromagnetic stimulation by means of the ... More
Joining and decomposing reaction networksOct 12 2018In systems and synthetic biology, much research has focused on the behavior and design of single pathways, while, more recently, experimental efforts have focused on how cross-talk (coupling two or more pathways) or inhibiting molecular function (isolating ... More