System Biology Research Papers - Academia.edu (original) (raw)

2025, IEEE Access

Most genetic networks, such as that for the biological clock, are part of much larger modules controlling fundamental processes in the cell, such as metabolism, development, and response to environmental signals. For example, the biological clock is part of a much larger network controlling the circadian rhythms of about 2418 distinct genes in the genome (with 11 000 genes) of the model system, Neurospora crassa. Predicting and understanding the dynamics of all of these genes and their products in a genetic network describing how the clock functions is a challenge and beyond the current capability of the fastest serial computers. We have implemented a novel variable-topology supernet ensemble method using Markov chain Monte Carlo simulations to fit and discover a regulatory network of unknown topology composed of 2418 genes describing the entire clock circadian network, a network that is found in organisms ranging from bacteria to humans, by harnessing the power of the general-purpose graphics processing unit and exploiting the hierarchical structure of that genetic network. The result is the construction of a genetic network that explains mechanistically how the biological clock functions in the filamentous fungus N. crassa and is validated against over 31 000 data points from microarray experiments. Two transcription factors are identified targeting ribosome biogenesis in the clock network. INDEX TERMS Biological clock, general-purpose graphical processing unit, ensemble method, supernet, systems biology, and regulatory network topologies.

2025

This article presents a brief overview of label-free optical biosensor-based cell assay technologies. Theoretical analysis suggests that a resonant waveguide grating (RWG) biosensor detects ligand-induced dynamic mass redistribution (DMR) within the bottom portion of an adherent cell layer. Pharmacological studies suggest that the DMR signal can serve as a novel physiological readout for monitoring receptor activation, and examining ligand pharmacology. Chemical biology studies support the hypothesis that the DMR signal is an integrated response that consists of contributions from many cellular events induced by the ligand, thus providing alternative means to study cell systems biology. Orthogonal confirmations using conventional cell biology approaches have led to identifying specific cellular event(s) that dominate the DMR signals observed for three classes of receptors: epidermal growth factor receptor, Gq-coupled receptors and Gs-coupled receptors.

2025, Nature Biotechnology

Measuring precise concentrations of proteins can provide insights into biological processes. Here, we use efficient protein extraction and sample fractionation and state-of-the-art quantitative mass spectrometry techniques to generate a comprehensive, condition-dependent protein abundance map of Escherichia coli. We measure cellular protein concentrations for 55% of predicted E. coli genes (>2300 proteins) under 22 different experimental conditions and identify methylation and N-terminal protein acetylations previously not known to be prevalent in bacteria. We uncover system-wide proteome allocation, expression regulation, and post-translational adaptations. These data provide a valuable resource for the systems biology and broader E. coli research communities.

2025, Microscopy and Microanalysis

Extended abstract of a paper presented at Microscopy and Microanalysis 2008 in Albuquerque, New Mexico, USA, August 3 – August 7, 2008

2025

G protein-coupled receptors (GPCRs) are targets of many drugs, of which ∼25% are indicated for central nervous system (CNS) disorders. Drug promiscuity affects their efficacy and safety profiles. Predicting the polypharmacology profile of compounds against GPCRs can thus provide a basis for producing more precise therapeutics by considering the targets and the antitargets in that family of closely related proteins. We provide a tool for predicting the polypharmacology of compounds within prominent GPCR families in the CNS: serotonin, dopamine, histamine, muscarinic, opioid, and cannabinoid receptors. Our inhouse algorithm, "iterative stochastic elimination" (ISE), produces high-quality ligand-based models for agonism and antagonism at 31 GPCRs. The ISE models correctly predict 68% of CNS drug-GPCR interactions, while the "similarity ensemble approach" predicts only 33%. The activity models correctly predict 56% of reported activities of DrugBank molecules for these CNS receptors. We conclude that the combination of interactions and activity profiles generated by screening through our models form the basis for subsequent designing and discovering novel therapeutics, either single, multitargeting, or repurposed.

2025, Clinical Rheumatology

Introduction Interleukin-1 receptor-associated kinases (IRAKs) are serine-threonine kinases involved in toll-like receptor and interleukin-1 signaling pathways. They play a key role in inflammation and innate immunity. IRAKs have been previously incriminated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis and inhibition of IRAKs has been recently regarded as a potential therapeutic strategy for SLE. Objectives The aim of the present study was to test the association between IRAK2 rs708035 and rs3844283 with SLE. Material and methods IRAK2 rs708035 and rs3844283 were genotyped by mutagenically separated polymerase chain reaction (MS-PCR) in 142 SLE patients and 149 age-and gender-matched controls. Results The hyperfunctional IRAK2 rs708035 A allele was more frequent among SLE patients than controls (62.9% versus 54.7%, p = 0.046). IRAK2 rs3844283 C allele was present in 66.5% of patients and 75.5% of controls. The CC genotype was the most frequently exhibited genotype. It was carried by 45.1% of patients with SLE and 57.7% of controls. The G allele was associated with an increased risk of SLE (OR = 1.54, 95%, CI = 1.07-2.22, p = 0.017). IRAK2 rs708035 and IRAK2 rs3844283 were in linkage disequilibrium (D′ = 0.64). The AG haplotype was more frequently observed in SLE patients than in controls (0.292 versus 0.194, p = 0.008). Conclusion This study for the first time ever reveals the association of IRAK2 rs708035 and IRAK2 rs3844283 and the corresponding haplotypes with SLE. Our findings give additional rationale to target IRAKs in the treatment of SLE. • IRAK2 rs708035 A allele is more frequent in SLE patients than in controls and IRAK2 rs3844283 G allele is associated with SLE susceptibility. • These two alleles are in linkage disequilibrium. • The AG haplotype is associated with SLE.

2025, Brain Research Bulletin

2025, Optimization Methods and Software

A recent breakthrough in application of experimental methods to biomedicine not only has already resulted in accumulation of massive amounts of data, but also created new challenges in the field of data mining. This paper addresses the issue by combining advanced data mining techniques with the novel application of systems biology t o study axonal regeneration and neurogenesis. To obtain the data for analysis, a series of biological experiments are conducted, in which the rat pheochromocytoma cell PC-12 was used as an appropriate model for neuronal differentiation. The resulting DNA microarray data set is studied using a combination of methods -a statistical procedure for feature selection together with a dimensionality reduction technique. First, we apply feature selection, which can be based either on the Wilcoxon rank-sum test, or on the two-sample t-test, depending on the statistical properties of the data. Next, we utilized an efficient dimensionality reduction procedure called correspondence analysis to obtain a two-dimensional projection of the data, which allows us to perform a visual exploration of the patterns as well as to select the features corresponding to the top down-regulated and up-regulated genes.

2025, American Journal of Respiratory Cell and Molecular Biology

The prevalence and morbidity of asthma, a chronic inflammatory airway disease, is increasing. Animal models provide a meaningful but limited view of the mechanisms of asthma in humans. A systemslevel view of asthma that integrates multiple levels of molecular and functional information is needed. For this, we compiled a gene expression compendium from five publicly available mouse microarray datasets and a gene knowledge base of 4,305 gene annotation sets. Using this collection we generated a high-level map of the functional themes that characterize animal models of asthma, dominated by innate and adaptive immune response. We used Module Networks analysis to identify co-regulated gene modules. The resulting modules reflect four distinct responses to treatment, including early response, general induction, repression, and IL-13-dependent response. One module with a persistent induction in response to treatment is mainly composed of genes with suggested roles in asthma, suggesting a similar role for other module members. Analysis of IL-13-dependent response using protein interaction networks highlights a role for TGF-b1 as a key regulator of asthma. Our analysis demonstrates the discovery potential of systems-level approaches and provides a framework for applying such approaches to asthma.

2025, TDX (Tesis Doctorals en Xarxa)

Pentose phosphate pathway Tricarboxilic acid gDCW Grams of dry cell weight AOX Alcohol oxidase Fab Antibody fragment NMR Nuclear magnetic resonance MFA Metabolic flux analysis HPLC High performance liquid chromatography LC-MS Liquid chromatography coupled with mass spectrometry GC-MS Gas chromatography coupled with mass spectrometry MAR Organic acids Glucose Unknown compound

2025

and Dave Kotterman presented "Artificial Closed Ecosystems for Human Habitation of Space" at the Rotary club of Lafayette on October 11. We received the second lighting array from Orbitec at the end of September. At that time the issue of light uniformity changing with increasing number of engines energized was addressed when the chip containing the software controlling driver function was upgraded with better software coding. This eliminated the problems encountered during preliminary testing of the first system. The first lighting system was upgraded to be identical to the performance of the second system at the time the second system was received. Trial 6 of the first system was ended prematurely due to mistakes with CO2 programming of the growth chamber, which led to uninterpretable results. Construction of a new mounting system to suspend the updated lightsicles (with eight that are 7" longer than the other eight to allow closer, staggered spacing) is underway. The new intracanopy mounting schematic will feature two Y-arrangements in the middle of the tub, and the remaining 10 lightsicles will be dispersed around the perimeter. Mounts have been constructed and mounting is underway. Following installation, new hardware calibration analyses will be performed and a side-by-side study with cowpea stands growing either with intracanopy or overhead LED lights will be conducted. 'Norland' potato explants are being cultivated for the second side-by-side IC vs. OH LED lighting experiment. Experiments with strawberry and sweetpotato are ongoing in the greenhouse. Strawberry fruit are harvested from the greenhouse and saved for antioxidant studies. Strawberry fruit from the temperature studies in the growth chambers are being harvested and eaten, and fruit are rated for flavor and quality. Ten types of carrots of varying color have been planted in tubs in the greenhouse. These will be used for antioxidant studies by Lisa Mauer's students. Preparations for testing of the pH control system are underway. A computer is being set up to log data of the control and monitoring system. Side-by-side tubs of Waldmann's green lettuce will be grown hydroponically in a walk-in growth chamber. One tub will be continuously adjusted for pH at intervals of 5 minutes automatically, with the duration (which can be converted to volume) of added solution (acid or base) logged. The second hydroponic system will be manually adjusted for pH every 48 hours. ESM for both procedures (power, crewtime) will be calculated and edible lettuce biomass produced will be compared after 30 days of growth.

2025

conducted a tour of the facilities and answered questions for an elementary school class researching advanced life support on December 1 st . Yang Yang, Gioia Massa, and Cary Mitchell met with Jerry Shephard in the Central Machine shop to discuss plans for the development of the cropcanopy gas-exchange cuvette system, Minitron III. In addition, discussions were pursued with Al Heber and Connie Li to determine what, if any, gas contaminants may be produced by the LED lighting system. Plans are underway to capture and analyze the cooling air passing through the lightsicles. Following an analysis of light output and current levels for both LED lighting systems, a side-by-side cowpea experiment was planted December 20 th in the growth chamber comparing intracanopy and overhead LED lighting. In addition, this experiment will be part of a collaboration with systems analyst Jim Russell to examine transpirational burdens under different lighting conditions. The conditions set for this experiment are 30 plants per growth area (0.23 m 2 ) with light levels set to approximately 300 µmols/m 2 /s at 2.5 cm from the light engines. Plants are being grown for 32 days, with pH and conductivity adjusted every other day. The treatments will be harvested January 20th. Lettuce plants were planted Dec. 21 st in a side-by-side comparison of manual versus automated hydroponic pH adjustment. This will be the first test with plants of the automated pH control system developed by Moeed Muhktar in George Chiu's lab. Harvests of experiments occurred November 29 th and December 15 th for carrot and December 7th for sweetpotato. Harvested biomass was sent to Lisa Mauer in Food Science for use in antioxidant studies. A second batch of carrots and sweetpotatoes has been replanted for replication. Final dry weight of paired basil/wheat straw residues composted with P. ostreatus 'Grey Dove' was taken and data analyzed. Samples were prepared for analyses of residual lignin content, cellulose and hemicellulose following 80-90 days of fungal colonization. In continuation of our collaborative work with the Food Safety team at AAMU, growth and maintenance of radish and lettuce using a nutrient film technique is on-going. Water samples from the nutrient film including leaf samples are being examined for waterborne food pathogens.

2025

Progress of each ALS-NSCORT project given by each project lead. 9 pages.

2025, Comparative and Functional Genomics

The genome of tomato (Solanum lycopersicum) is being sequenced by an international consortium of 10 countries (Korea, China, the United Kingdom, India, The Netherlands, France, Japan, Spain, Italy and the United States) as part of a larger initiative called the ‘International Solanaceae Genome Project (SOL): Systems Approach to Diversity and Adaptation’. The goal of this grassroots initiative, launched in November 2003, is to establish a network of information, resources and scientists to ultimately tackle two of the most significant questions in plant biology and agriculture: (1) How can a common set of genes/proteins give rise to a wide range of morphologically and ecologically distinct organisms that occupy our planet? (2) How can a deeper understanding of the genetic basis of plant diversity be harnessed to better meet the needs of society in an environmentally friendly and sustainable manner? The Solanaceae and closely related species such as coffee, which are included in the s...

2025, BMC Plant Biology

The natural environment for plants is composed of a complex set of abiotic stresses and biotic stresses. Plant responses to these stresses are equally complex. Systems biology approaches facilitate a multi-targeted approach by allowing one to identify regulatory hubs in complex networks. Systems biology takes the molecular parts (transcripts, proteins and metabolites) of an organism and attempts to fit them into functional networks or models designed to describe and predict the dynamic activities of that organism in different environments. In this review, research progress in plant responses to abiotic stresses is summarized from the physiological level to the molecular level. New insights obtained from the integration of omics datasets are highlighted. Gaps in our knowledge are identified, providing additional focus areas for crop improvement research in the future.

2025, Journal of Proteome Research

In the "Experimental Procedures" section of the paper, we mistakenly stated the peptide sequence used to generate antibodies specific for PP1β as 298-SEKKAKYGYGGLNG-312. The correct sequence we used was in fact 298-SEKKAKYQYGGLNSG-312. Although this error has no impact on any of the results or conclusions presented in the manuscript, we sincerely apologize for any inconvenience or confusion this might have caused.

2025, Physical Review E

The collective migration of cells in tissue pervades many important biological processes, such as wound healing, organism development, and cancer metastasis. Recent experiments on wound healing show that the collective migratory behavior of cells can be quite complex, including transient vortices and long-range correlations. Here, we explore cellular flows in epithelial tissues using a model that considers the force distribution and polarity of a single cell along with cell-cell adhesion. We show that the dipole nature of a crawling cell's force distribution destabilizes steady cellular motion. We determine the values of the physical parameters that are necessary to produce these complex motions and use numerical simulation to verify the linear analysis and to demonstrate the complex flows. We find that the tendency for cells to align is the dominant physical parameter that determines the stability of steady flows in the epithelium.

2025, Proceedings / ... International Conference on Intelligent Systems for Molecular Biology ; ISMB. International Conference on Intelligent Systems for Molecular Biology

The present methods for representing metabolic pathways are limited in their ability to handle complex systems, incorporate new information, and to provide for drawing qualitative conclusions from the structure of pathways. The theory of Petri nets is introduced as a tool for computer-implementable representation of pathways. Petri nets have the potential to overcome the present limitations, and through a multitude of properties, enable the preliminary qualitative analysis of pathways.

2025, Molecular Systems Biology

The interpretation of morphogen gradients is a pivotal concept in developmental biology, and several mechanisms have been proposed to explain how gene regulatory networks (GRNs) achieve concentration-dependent responses. However, the number of different mechanisms that may exist for cells to interpret morphogens, and the importance of design features such as feedback or local cell-cell communication, is unclear. A complete understanding of such systems will require going beyond a case-by-case analysis of real morphogen interpretation mechanisms and mapping out a complete GRN 'design space.' Here, we generate a first atlas of design space for GRNs capable of patterning a homogeneous field of cells into discrete gene expression domains by interpreting a fixed morphogen gradient. We uncover multiple very distinct mechanisms distributed discretely across the atlas, thereby expanding the repertoire of morphogen interpretation network motifs. Analyzing this diverse collection of mechanisms also allows us to predict that local cell-cell communication will rarely be responsible for the basic dose-dependent response of morphogen interpretation networks.

2025, Computational Systems Bioinformatics. CSB2003. Proceedings of the 2003 IEEE Bioinformatics Conference. CSB2003

Study of protein interaction networks is crucial to post-genomic systems biology. Aided by highthroughput screening technologies, biologists are rapidly accumulating protein-protein interaction data. Using a random yeast two-hybrid (R2H) process, we have performed large-scale yeast two-hybrid searches with approximately fifty thousand random human brain cDNA bait fragments against a human brain cDNA prey fragment library. From these searches, we have identified 13,656 unique protein-protein interaction pairs involving 4,473 distinct known human loci. In this paper, we have performed our initial characterization of the protein interaction network in human brain tissue. We have classified and characterized all identified interactions based on Gene Ontology (GO) annotation of interacting loci. We have also described the "scale-free" topological structure of the network.

2025, International Journal of Agent Technologies and Systems

Multi-scale modeling of complex biological systems remains a central challenge in the systems biology community. A method of dynamic knowledge representation known as agent-based modeling enables the study of higher level behavior emerging from discrete events performed by individual components. With the advancement of computer technology, agent-based modeling has emerged as an innovative technique to model the complexities of systems biology. In this work, the authors describe SPARK (Simple Platform for Agent-based Representation of Knowledge), a framework for agent-based modeling specifically designed for systems-level biomedical model development. SPARK is a stand-alone application written in Java. It provides a user-friendly interface, and a simple programming language for developing Agent-Based Models (ABMs). SPARK has the following features specialized for modeling biomedical systems: 1) continuous space that can simulate real physical space; 2) flexible agent size and shape that can represent the relative proportions of various cell types; 3) multiple spaces that can concurrently simulate and visualize multiple scales in biomedical models; 4) a convenient graphical user interface. Existing ABMs of diabetic foot ulcers and acute inflammation were implemented in SPARK. Models of identical complexity were run in both NetLogo and SPARK; the SPARK-based models ran two to three times faster.

2025

This poster presents first steps towards using symbolic models of signaling pathways in combination with statistical methods to analyze gene expression data. As a case study, data from 51 breast cancer cell lines is used.

2025, Journal of Theoretical Biology

Models for systems biology commonly adopt Differential Equations or Agent-Based modeling approaches for simulating the processes as a whole. Models based on differential equations presuppose phenomenological intracellular behavioral mechanisms, while models based on Multi-Agent approach often use directly translated, and quantitatively less precise if-then logical rule constructs. We propose an extendible systems model based on a hybrid agent-based approach where biological cells are modeled as individuals (agents) while molecules are represented by quantities. This hybridization in entity representation entails a combined modeling strategy with agent-based behavioral rules and differential equations, thereby balancing the requirements of extendible model granularity with computational tractability. We demonstrate the efficacy of this approach with models of chemotaxis involving an assay of 10 3 cells and 1.2 Â 10 6 molecules. The model produces cell migration patterns that are comparable to laboratory observations.

2025, BMC Systems Biology

Background: The metabolic transformation that changes Weddell seal pups born on land into aquatic animals is not only interesting for the study of general biology, but it also provides a model for the acquired and congenital muscle disorders which are associated with oxygen metabolism in skeletal muscle. However, the analysis of gene expression in seals is hampered by the lack of specific microarrays and the very limited annotation of known Weddell seal (Leptonychotes weddellii) genes. Results: Muscle samples from newborn, juvenile, and adult Weddell seals were collected during an Antarctic expedition. Extracted RNA was hybridized on Affymetrix Human Expression chips. Preliminary studies showed a detectable signal from at least 7000 probe sets present in all samples and replicates. Relative expression levels for these genes was used for further analysis of the biological pathways implicated in the metabolism transformation which occurs in the transition from newborn, to juvenile, to adult seals. Cytoskeletal remodeling, WNT signaling, FAK signaling, hypoxia-induced HIF1 activation, and insulin regulation were identified as being among the most important biological pathways involved in transformation. In spite of certain losses in specificity and sensitivity, the cross-species application of gene expression microarrays is capable of solving challenging puzzles in biology. A Systems Biology approach based on gene interaction patterns can compensate adequately for the lack of species-specific genomics information.

2025

This paper describes the use of a mixture of abduction and induction for the problem of identifying the effects of toxins in metabolic networks. Background knowledge is used which describes network topology and functional classes of enzymes. This background knowledge, which represents the present state of understanding, is incomplete. In order to overcome this incompleteness hypotheses are entertained which consist of a mixture of specific inhibitions of enzymes (ground facts) together with general rules which predict classes of enzymes likely to be inhibited by the toxin (nonground). The foreground examples were derived from in vivo experiments involving NMR analysis of time-varying metabolite concentrations in rat urine following injections of toxin. Hypotheses about inhibition are built using Progol5.0 and predictive accuracy is assessed for both the ground and the non-ground cases.

2025, BMC Neuroscience

Dynamic modeling and simulation of signal transduction pathways is an important topic in systems biology and is obtaining growing attention from researchers with experimental or theoretical background. Here we review attempts to analyze and model specific signaling systems. We review the structure of recurrent building blocks of signaling pathways and their integration into more comprehensive models, which enables the understanding of complex cellular processes. The variety of mechanisms found and modeling techniques used are illustrated with models of different signaling pathways. Focusing on the close interplay between experimental investigation of pathways and the mathematical representations of cellular dynamics, we discuss challenges and perspectives that emerge in studies of signaling systems. <p>Problems and tools in the systems biology of the neuronal cell</p> Sergio Nasi, Ivan Arisi, Antonino Cattaneo, Marta Cascante Reviews

2025, 2007 European Control Conference (ECC)

In this paper, we focus on discrete-time continuous-space Piecewise Affine (PWA) systems, and study properties of their trajectories expressed as temporal and logical statements over polyhedral regions. Specifically, given a PWA system and a Linear Temporal Logic (LTL) formula over linear predicates in its state variables, we attempt to find the largest region of initial states from which all trajectories of the system satisfy the formula. Our method is based on a classical algorithm for the iterative computation of simulation quotients augmented with model checking. We show that the determinism inherent in the problem and the particular linear structure of the invariants and of the dynamics can be exploited in a computationally attractive algorithm. We illustrate the application of our method to the computation of basins of attraction for the two equilibria of a PWA model of a two-gene network.

2025

Background: Bioremediation may offer the only feasible strategy for the nearly intractable problem of metal and radionuclide contamination of soil and groundwater. To understand bioremediation in contaminated environments, it is critical to determine the organisms present in these environments, analyze their responses to stress conditions, and elucidate functional position in the environment. Methods: We used multiple molecular techniques on both sediment and groundwater to develop a better understanding of the functional capability and stress level within the microbial community in relationship to over one hundred geochemical parameters. Due to the low pH (3.5-4.5) and high contaminant levels (e.g., uranium) microbial densities and activities were low. We used a phage polymerase amplification system to construct large and small insert DNA libraries, performed metagenome sequencing, constructed clonal libraries of select functional genes (SSU rRNA gene, nirK, nirS, amoA, pmoA, and dsrAB), used a SSU rDNA Phylochip microarray (9,000 taxa), and a functional gene array (23K genes). A complete comparison for community differences and similarities between the different techniques was assessed using several bioinformatics techniques. Results: SSU rDNA analysis revealed the presence of distinct bacterial phyla, including proteobacteria, acidobacteria, and planctomycetes along the contaminant gradient. Metagenome analysis identified many of the same organisms, and diversity was lower in water than sediment. Analysis with functional gene arrays, phylochip, and specific probes for genes and organisms involved in biogeochemical cycling of C, N, and S, metal resistance, stress response, and contaminant degradation suggested that the dominant species could be biostimulated during in situ uranium reduction. Several other findings of difference and similarities between methods are presented. Conclusion: These systems biology field studies could be enabling for strategies to attenuate nletal and radionuclide contamination.

2025, Elsevier eBooks

Most physiological processes are subjected to molecular regulation by growth factors, which are secreted proteins that activate chemical signal transduction pathways through binding of specific cell-surface receptors. One particular growth factor system involved in the in vivo regulation of blood vessel growth is called the vascular endothelial growth factor (VEGF) system. Computational and numerical techniques are well-suited to handle the molecular complexity (the number of binding partners involved, including ligands, receptors, and inert binding sites) and multi-scale nature (intra-tissue vs. inter-tissue transport and local vs. systemic effects within an organism) involved in modeling growth factor system interactions and effects. This paper introduces a variety of in silico models that seek to recapitulate different aspects of VEGF system biology at various spatial and temporal scales: molecular-level kinetic models focus on VEGF ligand-receptor interactions at and near the endothelial cell surface; meso-scale single-tissue 3D models can simulate the effects of multi-cellular tissue architecture on the spatial variation in VEGF ligand production and receptor activation; compartmental modeling allows efficient prediction of average interstitial VEGF concentrations and cell-surface VEGF signaling intensities across multiple large tissue volumes, permitting the investigation of whole-body inter-tissue transport (e.g., vascular permeability and lymphatic drainage). The given examples will demonstrate the utility of computational models in aiding both basic science and clinical research on VEGF systems biology.

2025

We present GKIN, a simulator and a comprehensive graphical interface where one can draw the model specification of reactions between hypothesized molecular participants in a gene regulatory and biochemical reaction network (or genetic network for short). The solver is written in C++ in a nearly platform independent manner to simulate large ensembles of models, which can run on PCs, Macintoshes, and UNIX machines, and its graphical user interface is written in Java which can run as a standalone or WebStart application. The drawing capability for rendering a network significantly enhances the ease of use of other reaction network simulators, such as KINSOLVER and enforces a correct semantic specification of the network. In a usability study with novice users, drawing the network with GKIN was preferred and faster in comparison with entry with a dialog-box guided interface in COPASI with no difference in error rates between GKIN and COPASI in specifying the network. GKIN is freely available at .

2025, HAL (Le Centre pour la Communication Scientifique Directe)

Rule-based modelling languages, such as Kappa, allow for the description of very detailed mechanistic models. Yet, as the rules become more and more numerous, there is a need for formal methods to enhance the level of confidence in the models that are described with these languages. We develop abstract interpretation tools to capture invariants about the biochemical structure of the biomolecular species that may occur in a given model. In previous works, we have focused on the relationships between the states of the sites that belong to the same instance of a protein. This comes down to detect for a specific set of patterns, which ones may be reachable during the execution of the model. In this paper, we generalise this approach to a broader family of abstract domains that we call orthogonal sets of patterns. More precisely, an orthogonal set of patterns is obtained by refining recursively the information about some patterns containing a given protein, so as to partition the set of occurrences of this protein in any mixture. We show that orthogonal sets of patterns offer a convenient choice to design scalable and accurate static analyses. As an example, we use them to infer properties in models with transport of molecules (more precisely, we show that each pair of proteins that are connected, always belong to the same compartment), and models involving double bindings (we show that whenever a protein of type A is bound twice to proteins of type B, then the protein A is necessarily bound twice to the same instance of the protein B).

2025, HAL (Le Centre pour la Communication Scientifique Directe)

Ce sont maintenant, chaque année, 180 millions d'hectares de variétés génétiquement modifiées qui sont cultivés par plus de 18 millions d'agriculteurs de 28 pays. Concernant l'alimentation, la réglementation européenne est la plus contraignante, et malgré les millions d'euros dépensés et les milliers de publications scientifiques qui attestent de leur innocuité, les tests requis pour l'évaluation des risques représentent encore des sommes que seules d'importantes firmes sont en mesure de payer. De récentes méthodes précises et ciblées permettent maintenant d'introduire des mutations dans le génome des plantes, sans y ajouter le moindre ADN étranger. Aux États-Unis, ces plantes ne sont pas soumises à la réglementation sur les organismes génétiquement modifiés (OGM). S'il ne devait pas en être ainsi chez nous, la biotechnologie végétale serait condamnée à demeurer inaccessible aux plus modestes semenciers et cultivateurs et, au mieux, nous importerions… Mots-clés : Organismes génétiquement modifiés (OGM) -plantes transgéniquessécurité alimentaire -évaluation du risque -édition/correction des génomes.

2025, Experimental Gerontology

Aging is a highly complex, multifactorial process. We use the yeast Saccharomyces cerevisiae as a model to study the mechanisms of cellular aging in multicellular eukaryotes. To address the inherent complexity of aging from a systems perspective and to build an integrative model of aging process, we investigated the effect of calorie restriction (CR), a low-calorie dietary regimen, on the metabolic history of chronologically aging yeast. We examined how CR influences the age-related dynamics of changes in the intracellular levels of numerous proteins and metabolites, carbohydrate and lipid metabolism, interorganellar metabolic flow, concentration of reactive oxygen species, mitochondrial morphology, essential oxidation-reduction processes in mitochondria, mitochondrial proteome, cardiolipin in the inner mitochondrial membrane, frequency of mitochondrial DNA mutations, dynamics of mitochondrial nucleoid, susceptibility to mitochondria-controlled apoptosis, and stress resistance. Based on the comparison of the metabolic histories of long-lived CR yeast and short-lived non-CR yeast, we propose that yeast define their long-term viability by designing a diet-specific pattern of metabolism and organelle dynamics prior to reproductive maturation. Thus, our data suggest that longevity in chronologically aging yeast is programmed by the level of metabolic capacity and organelle organization they developed, in a diet-specific fashion, prior to entry into a non-proliferative state.

2025, Progress in Biophysics and Molecular Biology

Symmetries play a major role in physics, in particular since the work by E. Noether and H. Weyl in the first half of last century. Herein, we briefly review their role by recalling how symmetry changes allow to conceptually move from classical to relativistic and quantum physics. We then introduce our ongoing theoretical analysis in biology and show that symmetries play a radically different role in this discipline, when compared to those in current physics. By this comparison, we stress that symmetries must be understood in relation to conservation and stability properties, as represented in the theories. We posit that the dynamics of biological organisms, in their various levels of organization, are not "just" processes, but permanent (extended, in our terminology) critical transitions and, thus, symmetry changes. Within the limits of a relative structural stability (or interval of viability), variability is at the core of these transitions.

2025

Average concentrations of glycolytic intermediates involved in the tryptophan (TRP) synthesis are of major importance in regulating and modulating the TRP synthesis. It is well known that oscillations of glycolytic intermediates often occur in living cells, according to the environment conditions and characteristics of the ATPrecovery system. As the TRP synthesis is connected to glycolysis through the PEP (phosphoenolpyruvate) node, the study of the major role played by the PEP glycolytic intermediate for the tryptophan (TRP) oscillatory metabolic synthesis is of high interest in industrial biosynthesis. Based on a reduced kinetic model for TRP synthesis from literature, this paper performs an in-silico analysis of the way by which the PEP level involved in the oscillatory glycolysis influences the TRP synthesis in E. coli bacteria. The analysis allows further TRP synthesis optimization.

2025, Advanced Nonlinear Studies

Let V be a finite-dimensional representation of a compact connected Lie group G and let ϕ : where ∇ v ϕ is the gradient of ϕ with respect to the first coordinate. Denote by V i a direct sum of eigenspaces of the isomorphism ∇ 2 v ϕ(0, λ i ) corresponding to positive eigenvalues, i = 1, 2. We have proved that We have proved that a global bifurcation and symmetrybreaking of solutions phenomenon occurs simultaneously for elliptic differential equations considered by Smoller and Wasserman in , which improves results of .

2025, BMC Systems Biology

Background: Smallpox is a lethal disease that was endemic in many parts of the world until eradicated by massive immunization. Due to its lethality, there are serious concerns about its use as a bioweapon. Here we analyze publicly available microarray data to further understand survival of smallpox infected macaques, using systems biology approaches. Our goal is to improve the knowledge about the progression of this disease. We used KEGG pathways annotations to define groups of genes (or modules), and subsequently compared them to macaque survival times. This technique provided additional insights about the host response to this disease, such as increased expression of the cytokines and ECM receptors in the individuals with higher survival times. These results could indicate that these gene groups could influence an effective response from the host to smallpox. Macaques with higher survival times clearly express some specific pathways previously unidentified using regular gene-by-gene approaches. Our work also shows how third party analysis of public datasets can be important to support new hypotheses to relevant biological problems.

2025, Biosystems

Understanding the relationship between the structural organization of intracellular decision networks and the observable phenotypes they control is one of the exigent problems of modern systems biology. Here we perform a systems analysis of a prototypic quorum sensing network whose operation allows bacterial populations to activate certain patterns of gene expression cooperatively. We apply structural perturbations to the model and analyze the resulting changes in the network behavior with the aim to identify the contribution of individual network elements to the functional fitness of the whole network. Specifically, we demonstrate the importance of the dimerization of the transcription factor and the presence of the auxiliary positive feedback loop on the switch-like behavior of the network and the stability of its "on" and "off" states under the influence of molecular noise.

2025

This paper explores the concept of form and structure in complex systems, focusing on their role in understanding the organization, evolution, and design of biological and physical systems. Drawing on methodologies from topology, morphology, and graph theory, we examine how the shape and connectivity of systems influence their behavior and development. The interplay between form, function, and evolution is discussed, with particular emphasis on how these principles inform modern technologies in artificial intelligence (AI), robotics, and synthetic biology. Through historical case studies and contemporary examples, we demonstrate how form and structure have shaped scientific theories and technological innovations. By bridging theoretical frameworks with practical applications, this paper highlights the relevance of data-driven design in addressing real-world challenges, particularly in the design of AI, robotics, and synthetic biology. Ultimately, we argue that understanding the relationship between form, structure, and function is crucial for advancing both scientific knowledge and the development of adaptive, resilient technologies.

2025

2025, arXiv (Cornell University)

2025, Progress in Biophysics and Molecular Biology

2025, Nucleic Acids Research

The Human Metabolome Database (HMDB, ) is a richly annotated resource that is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, nutritionists and members of the metabolomics community. Since its first release in 2007, the HMDB has been used to facilitate the research for nearly 100 published studies in metabolomics, clinical biochemistry and systems biology. The most recent release of HMDB (version 2.0) has been significantly expanded and enhanced over the previous release (version 1.0). In particular, the number of fully annotated metabolite entries has grown from 2180 to more than 6800 (a 300% increase), while the number of metabolites with biofluid or tissue concentration data has grown by a factor of five (from 883 to 4413). Similarly, the number of purified compounds with reference to NMR, LC-MS and GC-MS spectra has more than doubled (from 380 to more than 790 compounds). In addition to this significant expansion in database size, many new database searching tools and new data content has been added or enhanced. These include better algorithms for spectral searching and matching, more powerful chemical substructure searches, faster text searching software, as well as dedicated pathway searching tools and customized, clickable metabolic maps. Changes to the user-interface have also been implemented to accommodate future expansion and to make database navigation much easier. These improvements should make the HMDB much more useful to a much wider community of users.