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Biology subjects

Dutta, P. S.

Publications and source records attributed to Dutta, P. S..

10 recordsLinked to original sources

Early detection of sudden transitions in Notch signalling

Identifying sudden transitions during phenotypic decision-making of complex biological systems can be crucial for our ability to control a cellular state. Yet, prior determination of these sudden transitions or tipping points remains challenging, as biological systems often exhibit only subtle early changes, which are often masked by inherent noise or rapid transition dynamics. Using Notch signaling as a model, we systematically analyze dynamical transitions in Notch-Delta (ND), Notch-Delta-Jagged (NDJ), and Fringe-mediated NDJ systems for both one and two-cell contexts. In the one-cell ND system, critical slowing down (CSD)-based early warning signals (EWSs) reliably capture transitions between sender (S) and receiver (R) states and remain robust to variation in forcing rate. We further find that flickering is a precursor to transitions in one-cell NDJ system. In contrast, flickering does not occur in the two-cell Notch model due to the presence of a supercritical bifurcation. Our analysis also offers insight into how NICD (Notch Intracellular Domain)-driven and Fringe-mediated asymmetries, along with the strength of external signals, control the emergence of flickering. Overall, this study identifies sudden transitions in Notch signaling under demographic noise and can be extended to other noisy biological systems, with potential applications in drug development and targeted therapeutic interventions.

systems biology↗

Efficacy of dynamic eigenvalue in anticipating and distinguishing tipping points

The presence of tipping points in several natural systems necessitates having improved early warning indicators to provide accurate signals of an impending transition to a contrasting state while also detecting the type of transition. Various early warning signals (EWSs) have been devised to forecast the occurrence of tipping points, also called critical transitions. Dynamic eigenvalue (DEV) is a recently proposed EWS that can not only predict the occurrence of a transition but also certain types of accompanying bifurcations. Here, we study the effectiveness and limitations of DEV as an EWS for diverse kinds of critical phenomena. We demonstrate that DEV is a powerful EWS that shows promising results in anticipating catastrophic (first-order or discontinuous) and non-catastrophic (second-order or continuous) transitions in discrete and continuous dynamical systems. However, it falls short in the case of piecewise smooth systems. Further, the ability of DEV to forecast the type of transition is limited, as it cannot differentiate saddle-node bifurcation from transcritical and pitchfork bifurcations. Despite these limitations, we show that DEV can work as a robust indicator for varying rates at which the transition is approached and with systems involving colored noise.

ecology↗

Early warning signals are hampered by a lack of critical transitions in empirical lake data

Quantifying the potential for abrupt non-linear changes in ecological communities is a key managerial goal, leading to a significant body of research aimed at identifying indicators of approaching regime shifts. Most of this work has built on the theory of bifurcations, with the assumption that critical transitions are a common feature of complex ecological systems. This has led to the development of a suite of often inaccurate early warning signals (EWSs), with more recent techniques seeking to overcome their limitations by analysing multivariate time series or applying machine learning. However, it remains unclear whether regime shifts and/or critical transitions are common occurrences in natural systems, and - if they are present - whether classic and second-generation EWS methods predict rapid community change. Here, using multitrophic data on nine lakes from around the world, we both identify the type of transition a lake is exhibiting, and the reliability of classic and second generation EWSs methods to predict whole ecosystem change. We find few instances of critical transitions in our lake dataset, with different trophic levels often expressing different forms of abrupt change. The ability to predict this change is highly technique dependant, with multivariate EWSs generally classifying correctly, classical rolling window univariate EWSs performing not better than chance, and recently developed machine learning techniques performing poorly. Our results suggest that predictive ecology should start to move away from the concept of critical transitions and develop methods suitable for predicting change in the absence of the strict bounds of bifurcation theory.

ecology↗

Noise-induced symmetry breaking in a network of excitable ecological systems

Noise-induced symmetry breaking has barely been unveiled on the ecological grounds, though its occurrence may elucidate mechanisms responsible for maintaining biodiversity and ecosystem stability. Here, for a network of excitable consumer-resource systems, we show that the interplay of network structure and noise intensity manifests a transition from homogeneous steady state to inhomogeneous steady states, resulting in noise-induced symmetry breaking. On further increasing the noise intensity, there exist asynchronous oscillations, leading to heterogeneity crucial for maintaining a systems adaptive capacity. The observed collective dynamics can be understood analytically in the framework of linear stability analysis of the corresponding deterministic system.

ecology↗

Tipping points in spatial ecosystems driven by correlated noise

Complex spatial systems can experience critical transitions or tippings on crossing a threshold value in their response to stochastic perturbations. Whilst previous studies have well-characterized the impact of white noise on tipping, the effect of correlated noise in spatial ecosystems remains largely unexplored. Here, we investigate the effect of both multiplicative and additive Ornstein-Uhlenbeck (OU) correlated noise on the occurrence of critical transitions in spatial ecosystems. We find that decreasing the noise correlation aggravates the chance of critical transitions - opposite to what is observed previously in temporal systems in the presence of OU-noise with fixed lag-1 correlation. Our results hold good and are supported by the analysis of three well-studied spatial ecological models of varying nonlinearity. We also compute spatial early warning indicators (e.g., spatial variance, spatial skewness, and spatial correlation) to determine their reliability in anticipating tipping points with variations in noise correlation. The indicators of critical transitions exhibit mixed success in forewarning the occurrence of a tipping point, as indicated by the distribution of Kendalls rank correlation.

ecology↗

Rising Temperature Drives Tipping Points in Mutualistic Networks

The effect of climate warming on species physiological parameters, including growth rate, mortality rate, and handling time, is well established from empirical data. However, with an alarming rise in global temperature more than ever, predicting the interactive influence of these changes on mutualistic communities remains uncertain. Using 139 real plant-pollinator networks sampled across the globe and a modelling approach, we study the impact of species individual thermal responses on mutualistic communities. We show that at low mutualistic strength plant-pollinator networks are at potential risk of rapid transitions at higher temperatures. Evidently, generalist species plays a critical role in guiding tipping points in mutualistic networks. Further, we derive stability criteria for the networks in a range of temperatures using a two-dimensional reduced model. We identify network structures that can ascertain the delay of a community collapse. Until the end of this century, many real mutualistic networks can be under the threat of sudden collapse, and we frame strategies to mitigate them. Together, our results indicate that knowing individual species thermal responses and network structure can improve predictions for communities facing rapid transitions.

ecology↗

Machine learning methods trained on simple models can predict critical transitions in complex natural systems

1. Sudden transitions from one stable state to a contrasting state occur in complex systems ranging from the collapse of ecological populations to climatic change, with much recent work seeking to develop methods to predict these unexpected transitions from signals in time series data. However, previously developed methods vary widely in their reliability, and fail to classify whether an approaching collapse might be catastrophic (and hard to reverse) or non-catastrophic (easier to reverse) with significant implications for how such systems are managed. 2. Here we develop a novel detection method, using simulated outcomes from a range of simple mathematical models with varying nonlinearity to train a deep neural network to detect critical transitions - the Early Warning Signal Network (EWSNet). 3. We demonstrate that this neural network (EWSNet), trained on simulated data with minimal assumptions about the underlying structure of the system, can predict with high reliability observed real-world transitions in ecological and climatological data. Importantly, our model appears to capture latent properties in time series missed by previous warning signals approaches, allowing us to not only detect if a transition is approaching but critically whether the collapse will be catastrophic or non-catastrophic. 4. The EWSNet can flag a critical transition with unprecedented accuracy, overcoming some of the major limitations of traditional methods based on phenomena such as Critical Slowing Down. These novel properties mean EWSNet has the potential to serve as a universal indicator of transitions across a broad spectrum of complex systems, without requiring information on the structure of the system being monitored. Our work highlights the practicality of deep learning for addressing further questions pertaining to ecosystem collapse and have much broader management implications.

ecology↗

Persistence and stability of interacting species in response to climate warming: The role of trophic structure

Over the past century, the Earth has experienced roughly 0.4-0.8{degrees}C rise in the average temperature and which is projected to increase between 1.4-5.8{degrees}C by the year 2100. The increase in the Earths temperature directly influences physiological traits of individual species in ecosystems. However, the effect of these changes in community dynamics, so far, remains relatively unknown. Here we show that the consequences of warming (i.e., increase in the global mean temperature) on the interacting species persistence or extinction are correlated with their trophic complexity and community structure. In particular, we investigate different nonlinear bioenergetic tri-trophic food web modules, commonly observed in nature, in the order of increasing trophic complexity; a food chain, a diamond food web and an omnivorous interaction. We find that at low temperatures, warming can destabilize the species dynamics in the food chain as well as the diamond food web, but it has no such effect on the trophic structure that involves omnivory. In the diamond food web, our results indicate that warming does not support top-down control induced co-existence of intermediate species. However, in all the trophic structures warming can destabilize species up to a threshold temperature. Beyond the threshold temperature, warming stabilizes species dynamics at the cost of the extinction of higher trophic species. We demonstrate the robustness of our results when a few system parameters are varied together with the temperature. Overall, our study suggests that variations in the trophic complexity of simple food web modules can influence the effects of climate warming on species dynamics.

ecology↗

Anticipating critical transitions in epithelial-hybrid-mesenchymal cell-fate determination

In the vicinity of a tipping point, critical transitions occur when small changes in an input condition causes sudden, large and often irreversible changes in the state of a system. Many natural systems ranging from ecosystems to molecular biosystems are known to exhibit critical transitions in their response to stochastic perturbations. In diseases, an early prediction of upcoming critical transitions from a healthy to a disease state by using early warning signals is of prime interest due to potential application in forecasting disease onset. Here, we analyze cell-fate transitions between different phenotypes (epithelial, hybrid epithelial/mesenchymal (E/M) and mesenchymal states) that are implicated in cancer metastasis and chemoresistance. These transitions are mediated by a mutually inhibitory feedback loop microRNA-200/ZEB driven by the levels of transcription factor SNAIL. We find that the proximity to tipping points enabling these transitions among different phenotypes can be captured by critical slowing down based early warning signals, calculated from the trajectory of ZEB mRNA level. Further, the basin stability analysis reveals the unexpectedly large basin of attraction for a hybrid E/M phenotype. Finally, we identified mechanisms that can potentially elude the transition to a hybrid E/M phenotype. Overall, our results unravel the early warning signals that can be used to anticipate upcoming epithelial-hybrid-mesenchymal transitions. With the emerging evidence about the hybrid E/M phenotype being a key driver of metastasis, drug resistance, and tumor relapse; our results suggest ways to potentially evade these transitions, reducing the fitness of cancer cells and restricting tumor aggressiveness.\n\nSignificance StatementEpithelial-hybrid-mesenchymal transitions play critical roles in cancer metastasis, drug resistance, and tumor relapse. Recent studies have proposed that cells in a hybrid epithelial/mesenchymal phenotype may be more aggressive than those on either end of the spectrum. However, no biomarker to predict upcoming transitions has been identified. Here, we show that critical slowing down based early warning signals can detect sudden transitions among epithelial, hybrid E/M, and mesenchymal phenotypes. Importantly, our results highlight how stable a hybrid E/M phenotype can be, and how can a transition to this state be avoided. Thus, our study provides valuable insights into restricting cellular plasticity en route metastasis.

systems biology↗

Robustness of early warning signals for catastrophic and non-catastrophic transitions

Early warning signals (EWS) are statistical indicators that a rapid regime shift may be forthcoming. Their development has given ecologists hope of predicting rapid regime shifts before they occur. Accurate predictions, however, rely on the signals being appropriate to the system in question. Most of the EWS commonly applied in ecology have been studied in the context of one specific type of regime shift (the type brought on by a saddle-node bifurcation, at which one stable equilibrium point collides with an unstable equilibrium and disappears) under one particular perturbation scheme (temporally uncorrelated noise that perturbs the net population growth rate in a density independent way). Whether and when these EWS can be applied to other ecological situations remains relatively unknown, and certainly underappreciated. We study a range of models with different types of dynamical transitions (including rapid regime shifts) and several perturbation schemes (density-dependent uncorrelated or temporally-correlated noise) and test the ability of EWS to warn of an approaching transition. We also test the sensitivity of our results to the amount of available pre-transition data and various decisions that must be made in the analysis (i.e. the rolling window size and smoothing bandwidth used to compute the EWS). We find that EWS generally work well to signal an impending saddle-node bifurcation, regardless of the autocorrelation or intensity of the noise. However, EWS do not reliably appear as expected for other types of transition. EWS were often very sensitive to the length of the pre-transition time series analyzed, and usually less sensitive to other decisions. We conclude that the EWS perform well for saddle-node bifurcation in a range of noise environments, but different methods should be used to predict other types of regime shifts. As a consequence, knowledge of the mechanism behind a possible regime shift is needed before EWS can be used to predict it.

ecology↗