{"title":"Asymptotic analysis for stationary distributions of scaled reaction networks","authors":"Linard Hoessly, Carsten Wiuf, Panqiu Xia","doi":"arxiv-2402.02276","DOIUrl":"https://doi.org/arxiv-2402.02276","url":null,"abstract":"We study stationary distributions in the context of stochastic reaction\u0000networks. In particular, we are interested in complex balanced reaction\u0000networks and reduction of such networks by assuming a set of species (called\u0000non-interacting species) are degraded fast (and therefore essentially absent in\u0000the network), implying some reaction rates are large compared to others.\u0000Technically, we assume these reaction rates are scaled by a common parameter\u0000$N$ and let $Ntoinfty$. The limiting stationary distribution as $Ntoinfty$\u0000is compared to the stationary distribution of the reduced reaction network\u0000obtained by algebraic elimination of the non-interacting species. In general,\u0000the limiting stationary distribution might differ from the stationary\u0000distribution of the reduced reaction network. We identify various sufficient\u0000conditions for when these two distributions are the same, including when the\u0000reaction network is detailed balanced and when the set of non-interacting\u0000species consists of intermediate species. In the latter case, the limiting\u0000stationary distribution essentially retains the form of the complex balanced\u0000distribution. This finding is particularly surprising given that the reduced\u0000reaction network might be non-weakly reversible and exhibit unconventional\u0000kinetics.","PeriodicalId":501325,"journal":{"name":"arXiv - QuanBio - Molecular Networks","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139758441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Test of the formal basis of Arrhenius law with heat capacities","authors":"Denis Michel","doi":"arxiv-2402.00900","DOIUrl":"https://doi.org/arxiv-2402.00900","url":null,"abstract":"The exponential factor of Arrhenius satisfactorily quantifies the energetic\u0000restriction of chemical reactions but is still awaiting a rigorous basis.\u0000Assuming that the Arrhenius equation should be based on statistical mechanics\u0000and is probabilistic in nature, two structures for this equation are compared,\u0000depending on whether the reactant energies are viewed as the mean values of\u0000specific energy distributions or as particular levels in a global energy\u0000distribution. In the first version, the Arrhenius exponential factor would be a\u0000probability that depends once on temperature, while in the second it is a ratio\u0000of probabilities that depends twice on temperature. These concurrent equations\u0000are tested using experimental data for the isomerization of 2-butene. This\u0000comparison reveals the fundamental structure of the Arrhenius law in isothermal\u0000systems and overlooked properties resulting from the introduction of reactant\u0000energies into the equation.","PeriodicalId":501325,"journal":{"name":"arXiv - QuanBio - Molecular Networks","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139772840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functional approach to the catalytic site of the sarcoplasmic reticulum Ca(2+)-ATPase: binding and hydrolysis of ATP in the absence of Ca(2+)","authors":"A Lax, F Soler, F Fernandez Belda","doi":"arxiv-2401.17382","DOIUrl":"https://doi.org/arxiv-2401.17382","url":null,"abstract":"Isolated sarcoplasmic reticulum vesicles in the presence of Mg(2+) and\u0000absence of Ca(2+) retain significant ATP hydrolytic activity that can be\u0000attributed to the Ca(2+)-ATPase protein. At neutral pH and the presence of 5 mM\u0000Mg(2+), the dependence of the hydrolysis rate on a linear ATP concentration\u0000scale can be fitted by a single hyperbolic function. MgATP hydrolysis is\u0000inhibited by either free Mg(2+) or free ATP. The rate of ATP hydrolysis is not\u0000perturbed by vanadate, whereas the rate of p-nitrophenyl phosphate hydrolysis\u0000is not altered by a nonhydrolyzable ATP analog. ATP binding affinity at neutral\u0000pH and in a Ca(2+)-free medium is increased by Mg(2+) but decreased by vanadate\u0000when Mg(2+) is present. It is suggested that MgATP hydrolysis in the absence of\u0000Ca(2+) requires some optimal adjustment of the enzyme cytoplasmic domains. The\u0000Ca(2+)-independent activity is operative at basal levels of cytoplasmic Ca(2+)\u0000or when the Ca(2+) binding transition is impeded.","PeriodicalId":501325,"journal":{"name":"arXiv - QuanBio - Molecular Networks","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139657430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dissecting the Hydrolytic Activities of Sarcoplasmic Reticulum ATPase in the Presence of Acetyl Phosphate","authors":"F Soler, MI Fortea, A Lax, F Fernandez Belda","doi":"arxiv-2401.17375","DOIUrl":"https://doi.org/arxiv-2401.17375","url":null,"abstract":"Sarcoplasmic reticulum vesicles and purified Ca$^{2+}$-ATPase hydrolyze\u0000acetyl phosphate both in the presence and absence of Ca$^{2+}$. The\u0000Ca$^{2+}$-independent activity was fully sensitive to vanadate, insensitive to\u0000thapsigargin, and proceeded without accumulation of phosphorylated enzyme.\u0000Acetyl phosphate hydrolysis in the absence of Ca$^{2+}$ was activated by\u0000dimethyl sulfoxide. The Ca$^{2+}$-dependent activity was partially sensitive to\u0000vanadate, fully sensitive to thapsigargin, and associated with steady\u0000phosphoenzyme accumulation. The Ca$^{2+}$/P(i) coupling ratio at neutral pH\u0000sustained by 10 mm acetyl phosphate was 0.57. Addition of 30% dimethyl\u0000sulfoxide completely blocked Ca$^{2+}$ transport and partially inhibited the\u0000hydrolysis rate. Uncoupling induced by dimethyl sulfoxide included the\u0000accumulation of vanadate-insensitive phosphorylated enzyme. When acetyl\u0000phosphate was the substrate, the hydrolytic pathway was dependent on\u0000experimental conditions that might or might not allow net Ca$^{2+}$ transport.\u0000The interdependence of both Ca$^{2+}$-dependent and Ca$^{2+}$-independent\u0000hydrolytic activities was demonstrated.","PeriodicalId":501325,"journal":{"name":"arXiv - QuanBio - Molecular Networks","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139657561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Temperature Compensation through Kinetic Regulation in Biochemical Oscillators","authors":"Haochen Fu, Chenyi Fei, Qi Ouyang, Yuhai Tu","doi":"arxiv-2401.13960","DOIUrl":"https://doi.org/arxiv-2401.13960","url":null,"abstract":"Nearly all circadian clocks maintain a period that is insensitive to\u0000temperature changes, a phenomenon known as temperature compensation (TC). Yet,\u0000it is unclear whether there is any common feature among different systems that\u0000exhibit TC. From a general timescale invariance, we show that TC relies on\u0000existence of certain period-lengthening reactions wherein the period of the\u0000system increases strongly with the rates in these reactions. By studying\u0000several generic oscillator models, we show that this counter-intuitive\u0000dependence is nonetheless a common feature of oscillators in the nonlinear\u0000(far-from-onset) regime where the oscillation can be separated into fast and\u0000slow phases. The increase of the period with the period-lengthening reaction\u0000rates occurs when the amplitude of the slow phase in the oscillation increases\u0000with these rates while the progression-speed in the slow phase is controlled by\u0000other rates of the system. The positive dependence of the period on the\u0000period-lengthening rates balances its inverse dependence on other kinetic rates\u0000in the system, which gives rise to robust TC in a wide range of parameters. We\u0000demonstrate the existence of such period-lengthening reactions and their\u0000relevance for TC in all four model systems we considered. Theoretical results\u0000for a model of the Kai system are supported by experimental data. A study of\u0000the energy dissipation also shows that better TC performance requires higher\u0000energy consumption. Our study unveils a general mechanism by which a\u0000biochemical oscillator achieves TC by operating at regimes far from the onset\u0000where period-lengthening reactions exist.","PeriodicalId":501325,"journal":{"name":"arXiv - QuanBio - Molecular Networks","volume":"156 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Murrugarra, Alan Veliz-Cuba, Elena Dimitrova, Claus Kadelka, Matthew Wheeler, Reinhard Laubenbacher
{"title":"Modular Control of Biological Networks","authors":"David Murrugarra, Alan Veliz-Cuba, Elena Dimitrova, Claus Kadelka, Matthew Wheeler, Reinhard Laubenbacher","doi":"arxiv-2401.12477","DOIUrl":"https://doi.org/arxiv-2401.12477","url":null,"abstract":"The concept of control is central to understanding and applications of\u0000biological network models. Some of their key structural features relate to\u0000control functions, through gene regulation, signaling, or metabolic mechanisms,\u0000and computational models need to encode these. Applications of models often\u0000focus on model-based control, such as in biomedicine or metabolic engineering.\u0000This paper presents an approach to model-based control that exploits two common\u0000features of biological networks, namely their modular structure and canalizing\u0000features of their regulatory mechanisms. The paper focuses on intracellular\u0000regulatory networks, represented by Boolean network models. A main result of\u0000this paper is that control strategies can be identified by focusing on one\u0000module at a time. This paper also presents a criterion based on canalizing\u0000features of the regulatory rules to identify modules that do not contribute to\u0000network control and can be excluded. For even moderately sized networks,\u0000finding global control inputs is computationally very challenging. The modular\u0000approach presented here leads to a highly efficient approach to solving this\u0000problem. This approach is applied to a published Boolean network model of blood\u0000cancer large granular lymphocyte (T-LGL) leukemia to identify a minimal control\u0000set that achieves a desired control objective.","PeriodicalId":501325,"journal":{"name":"arXiv - QuanBio - Molecular Networks","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139558884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chuanbo Liu, Yu Fu, Lu Lin, Elliot L. Elson, Jin Wang
{"title":"Understanding Cellular Noise with Optical Perturbation and Deep Learning","authors":"Chuanbo Liu, Yu Fu, Lu Lin, Elliot L. Elson, Jin Wang","doi":"arxiv-2401.12498","DOIUrl":"https://doi.org/arxiv-2401.12498","url":null,"abstract":"Noise plays a crucial role in the regulation of cellular and organismal\u0000function and behavior. Exploring noise's impact is key to understanding fundamental biological\u0000processes, such as gene expression, signal transduction, and the mechanisms of\u0000development and evolution. Currently, a comprehensive method to quantify dynamical behavior of cellular\u0000noise within these biochemical systems is lacking. In this study, we introduce an optically-controlled perturbation system\u0000utilizing the light-sensitive Phytochrome B (PhyB) from textit{Arabidopsis\u0000thaliana}, which enables precise noise modulation with high spatial-temporal\u0000resolution. Our system exhibits exceptional sensitivity to light, reacting consistently\u0000to pulsed light signals, distinguishing it from other photoreceptor-based\u0000promoter systems that respond to a single light wavelength. To characterize our system, we developed a stochastic model for phytochromes\u0000that accounts for photoactivation/deactivation, thermal reversion, and the\u0000dynamics of the light-activated gene promoter system. To precisely control our system, we determined the rate constants for this\u0000model using an omniscient deep neural network that can directly map rate\u0000constant combinations to time-dependent state joint distributions. By adjusting the activation rates through light intensity and degradation\u0000rates via N-terminal mutagenesis, we illustrate that out optical-controlled\u0000perturbation can effectively modulate molecular expression level as well as\u0000noise. Our results highlight the potential of employing an optically-controlled gene\u0000perturbation system as a noise-controlled stimulus source. This approach, when combined with the analytical capabilities of a\u0000sophisticated deep neural network, enables the accurate estimation of rate\u0000constants from observational data in a broad range of biochemical reaction\u0000networks.","PeriodicalId":501325,"journal":{"name":"arXiv - QuanBio - Molecular Networks","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139558881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikolaos Ntetsikas, Styliana Kyriakoudi, Antonis Kirmizis, Bige Deniz Unluturk, Andreas Pitsillides, Ian F. Akyildiz, Marios Lestas
{"title":"Engineering Yeast Cells to Facilitate Information Exchange","authors":"Nikolaos Ntetsikas, Styliana Kyriakoudi, Antonis Kirmizis, Bige Deniz Unluturk, Andreas Pitsillides, Ian F. Akyildiz, Marios Lestas","doi":"arxiv-2401.13712","DOIUrl":"https://doi.org/arxiv-2401.13712","url":null,"abstract":"Although continuous advances in theoretical modelling of Molecular\u0000Communications (MC) are observed, there is still an insuperable gap between\u0000theory and experimental testbeds, especially at the microscale. In this paper,\u0000the development of the first testbed incorporating engineered yeast cells is\u0000reported. Different from the existing literature, eukaryotic yeast cells are\u0000considered for both the sender and the receiver, with {alpha}-factor molecules\u0000facilitating the information transfer. The use of such cells is motivated\u0000mainly by the well understood biological mechanism of yeast mating, together\u0000with their genetic amenability. In addition, recent advances in yeast\u0000biosensing establish yeast as a suitable detector and a neat interface to\u0000in-body sensor networks. The system under consideration is presented first, and\u0000the mathematical models of the underlying biological processes leading to an\u0000end-to-end (E2E) system are given. The experimental setup is then described and\u0000used to obtain experimental results which validate the developed mathematical\u0000models. Beyond that, the ability of the system to effectively generate output\u0000pulses in response to repeated stimuli is demonstrated, reporting one event per\u0000two hours. However, fast RNA fluctuations indicate cell responses in less than\u0000three minutes, demonstrating the potential for much higher rates in the future.","PeriodicalId":501325,"journal":{"name":"arXiv - QuanBio - Molecular Networks","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sebastian Lobentanzer, Pablo Rodriguez-Mier, Stefan Bauer, Julio Saez-Rodriguez
{"title":"Molecular causality in the advent of foundation models","authors":"Sebastian Lobentanzer, Pablo Rodriguez-Mier, Stefan Bauer, Julio Saez-Rodriguez","doi":"arxiv-2401.09558","DOIUrl":"https://doi.org/arxiv-2401.09558","url":null,"abstract":"Correlation is not causation. As simple as this widely agreed-upon statement\u0000may seem, scientifically defining causality and using it to drive our modern\u0000biomedical research is immensely challenging. In this perspective, we attempt\u0000to synergise the partly disparate fields of systems biology, causal reasoning,\u0000and machine learning, to inform future approaches in the field of systems\u0000biology and molecular networks.","PeriodicalId":501325,"journal":{"name":"arXiv - QuanBio - Molecular Networks","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139497392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ting-He Zhang, Sumin Jo, Michelle Zhang, Kai Wang, Shou-Jiang Gao, Yufei Huang
{"title":"Understanding YTHDF2-mediated mRNA Degradation By m6A-BERT-Deg","authors":"Ting-He Zhang, Sumin Jo, Michelle Zhang, Kai Wang, Shou-Jiang Gao, Yufei Huang","doi":"arxiv-2401.08004","DOIUrl":"https://doi.org/arxiv-2401.08004","url":null,"abstract":"N6-methyladenosine (m6A) is the most abundant mRNA modification within\u0000mammalian cells, holding pivotal significance in the regulation of mRNA\u0000stability, translation, and splicing. Furthermore, it plays a critical role in\u0000the regulation of RNA degradation by primarily recruiting the YTHDF2 reader\u0000protein. However, the selective regulation of mRNA decay of the m6A-methylated\u0000mRNA through YTHDF2 binding is poorly understood. To improve our understanding,\u0000we developed m6A-BERT-Deg, a BERT model adapted for predicting YTHDF2-mediated\u0000degradation of m6A-methylated mRNAs. We meticulously assembled a high-quality\u0000training dataset by integrating multiple data sources for the HeLa cell line.\u0000To overcome the limitation of small training samples, we employed a\u0000pre-training-fine-tuning strategy by first performing a self-supervised\u0000pre-training of the model on 427,760 unlabeled m6A site sequences. The test\u0000results demonstrated the importance of this pre-training strategy in enabling\u0000m6A-BERT-Deg to outperform other benchmark models. We further conducted a\u0000comprehensive model interpretation and revealed a surprising finding that the\u0000presence of co-factors in proximity to m6A sites may disrupt YTHDF2-mediated\u0000mRNA degradation, subsequently enhancing mRNA stability. We also extended our\u0000analyses to the HEK293 cell line, shedding light on the context-dependent\u0000YTHDF2-mediated mRNA degradation.","PeriodicalId":501325,"journal":{"name":"arXiv - QuanBio - Molecular Networks","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139481746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}