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Alexey Zaikin

Publications and source records attributed to Alexey Zaikin.

13 recordsLinked to original sources

Construction and simulation of a path-valued model of dendrite development

Neurons receive information through their dendrites. During development, when synaptic connections are forming, dendrites grow, retract, and branch. The resulting dendritic tree shapes the structure of the broader neural network. Crucially, retraction and branching make it necessary to track whole dendritic paths rather than only their endpoints. While this is handled implicitly in some existing simulations, here we construct an explicitly path-valued stochastic process for dendrite growth. Combining this with a branching process, using ideas from measure-valued branching particle systems, we show that the model produces the typical tree structures of real dendrites. To complement this analytical work, we also outline several methods for numerical simulation, including time discretisations at different temporal scales and an approximation using a dynamic graph. This provides both a more rigorous mathematical framework and more structured simulation methods for modelling dendrite development.

math.PR

Ensemble-based graph representation of fMRI data for cognitive brain state classification

fMRI is a non-invasive technique for investigating brain activity, offering high-resolution insights into neural processes. Understanding and decoding cognitive brain states from fMRI depends on how functional interactions are represented. We propose an ensemble-based graph representation in which each edge weight encodes state evidence as the difference between posterior probabilities of two states, estimated by an ensemble of edge-wise probabilistic classifiers from simple pairwise time-series features. We evaluate the method on seven task-fMRI paradigms from the Human Connectome Project, performing binary classification within each paradigm. Using compact node summaries (mean incident edge weights) and logistic regression, we obtain average accuracies of 97.07-99.74 %. We further compare ensemble graphs with conventional correlation graphs using the same graph neural network classifier; ensemble graphs consistently yield higher accuracy (88.00-99.42 % vs 61.86-97.94 % across tasks). Because edge weights have a probabilistic, state-oriented interpretation, the representation supports connection- and region-level interpretability and can be extended to multiclass decoding, regression, other neuroimaging modalities, and clinical classification.

q-bio.NC

Astrocytes mediate analogous memory in a multi-layer neuron-astrocytic network

Modeling the neuronal processes underlying short-term working memory remains the focus of many theoretical studies in neuroscience. Here we propose a mathematical model of spiking neuron network (SNN) demonstrating how a piece of information can be maintained as a robust activity pattern for several seconds then completely disappear if no other stimuli come. Such short-term memory traces are preserved due to the activation of astrocytes accompanying the SNN. The astrocytes exhibit calcium transients at a time scale of seconds. These transients further modulate the efficiency of synaptic transmission and, hence, the firing rate of neighboring neurons at diverse timescales through gliotransmitter release. We show how such transients continuously encode frequencies of neuronal discharges and provide robust short-term storage of analogous information. This kind of short-term memory can keep operative information for seconds, then completely forget it to avoid overlapping with forthcoming patterns. The SNN is inter-connected with the astrocytic layer by local inter-cellular diffusive connections. The astrocytes are activated only when the neighboring neurons fire quite synchronously, e.g. when an information pattern is loaded. For illustration, we took greyscale photos of people's faces where the grey level encoded the level of applied current stimulating the neurons. The astrocyte feedback modulates (facilitates) synaptic transmission by varying the frequency of neuronal firing. We show how arbitrary patterns can be loaded, then stored for a certain interval of time, and retrieved if the appropriate clue pattern is applied to the input.

q-bio.NC

Symmetry in cancer networks identified: Proposal for multi-cancer biomarkers

One of the most challenging problems in biomedicine and genomics is the identification of disease biomarkers. In this study, proteomics data from seven major cancers were used to construct two weighted protein-protein interaction (PPI) networks i.e., one for the normal and another for the cancer conditions. We developed rigorous, yet mathematically simple, methodology based on the degeneracy at -1 eigenvalues to identify structural symmetry or motif structures in network. Utilising eigenvectors corresponding to degenerate eigenvalues in the weighted adjacency matrix, we identified structural symmetry in underlying weighted PPI networks constructed using seven cancer data. Functional assessment of proteins forming these structural symmetry exhibited the property of cancer hallmarks. Survival analysis refined further this protein list proposing BMI, MAPK11, DDIT4, CDKN2A, and FYN as putative multi-cancer biomarkers. The combined framework of networks and spectral graph theory developed here can be applied to identify symmetrical patterns in other disease networks to predict proteins as potential disease biomarkers.

q-bio.MN

Integrated Information in the Spiking-Bursting Stochastic Model

This study presents a comprehensive analytic description in terms of the empirical "whole minus sum" version of Integrated Information in comparison to the "decoder based" version for the "spiking-bursting" discrete-time, discrete-state stochastic model, which was recently introduced to describe a specific type of dynamics in a neuron-astrocyte network. The "whole minus sum" information may change sign, and an interpretation of this transition in terms of "net synergy" is available in the literature. This motivates our particular interest to the sign of the "whole minus sum" information in our analytical consideration. The behavior of the "whole minus sum" and "decoder based" information measures are found to bear a lot of similarity, showing their mutual asymptotic convergence as time-uncorrelated activity is increased, with the sign transition of the "whole minus sum" information associated to a rapid growth in the "decoder based" information. The study aims at creating a theoretical base for using the spiking-bursting model as a well understood reference point for applying Integrated Information concepts to systems exhibiting similar bursting behavior (in particular, to neuron-astrocyte networks). The model can also be of interest as a new discrete-state test bench for different formulations of Integrated Information.

q-bio.NC

Astrocyte-induced positive integrated information in neuroglial ensembles

The Integrated Information is a quantitative measure from information theory how tightly all parts of a system are interconnected in terms of information exchange. In this study we show that astrocyte, playing an important role in regulation of information transmission between neurons, may contribute to a generation of positive Integrated Information in neuronal ensembles. Analytically and numerically we show that the presence of astrocyte may be essential for this information attribute in neuro-astrocytic ensembles. Moreover, the proposed "spiking-bursting" mechanism of generating positive Integrated Information is shown to be generic and not limited to neuroglial networks, and is given a complete analytic description.

q-bio.NC

Sensitivity of asymmetric rate-dependent critical systems to initial conditions: insights into cellular decision making

The work reported here aims to address the effects of time-dependent parameters and stochasticity on decision-making in biological systems. We achieve this by extending previous studies that resorted to simple normal forms. Yet, we focus primarily on the issue of the system's sensitivity to initial conditions in the presence of different noise distributions. In addition, we assess the impact of two-way sweeping through the critical region of a canonical Pitchfork bifurcation with a constant external asymmetry. The parallel with decision-making in bio-circuits is performed on this simple system since it is equivalent in its available states and dynamics to more complex genetic circuits. Overall, we verify that rate-dependent effects are specific to particular initial conditions. Information processing for each starting state is affected by the balance between sweeping speed through critical regions, and the type of fluctuations added. For a heavy-tail noise, forward-reverse dynamic bifurcations are more efficient in processing the information contained in external signals, when compared to the system relying on escape dynamics, if it starts at an attractor not favoured by the asymmetry and, in conjunction, if the sweeping amplitude is large.

q-bio.QM

Parenclitic network analysis of methylation data for cancer identification

We make use of ideas from the theory of complex networks to implement a machine learning classification of human DNA methylation data, that carry signatures of cancer development. The data were obtained from patients with various kinds of cancers and represented as parenclictic networks, wherein nodes correspond to genes, and edges are weighted according to pairwise variation from control group subjects. We demonstrate that for the $10$ types of cancer under study, it is possible to obtain a high performance of binary classification between cancer-positive and negative samples based on network measures. Remarkably, an accuracy as high as $93-99\%$ is achieved with only $12$ network topology indices, in a dramatic reduction of complexity from the original $15295$ gene methylation levels. Moreover, it was found that the parenclictic networks are scale-free in cancer-negative subjects, and deviate from the power-law node degree distribution in cancer. The node centrality ranking and arising modular structure could provide insights into the systems biology of cancer.

q-bio.GN

Detection of Epigenomic Network Community Oncomarkers

In this paper we propose network methodology to infer prognostic cancer biomarkers based on the epigenetic pattern DNA methylation. Epigenetic processes such as DNA methylation reflect environmental risk factors, and are increasingly recognised for their fundamental role in diseases such as cancer. DNA methylation is a gene-regulatory pattern, and hence provides a means by which to assess genomic regulatory interactions. Network models are a natural way to represent and analyse groups of such interactions. The utility of network models also increases as the quantity of data and number of variables increase, making them increasingly relevant to large-scale genomic studies. We propose methodology to infer prognostic genomic networks from a DNA methylation-based measure of genomic interaction and association. We then show how to identify prognostic biomarkers from such networks, which we term `network community oncomarkers'. We illustrate the power of our proposed methodology in the context of a large publicly available breast cancer dataset.

stat.AP

An iterative importance sampler for Bayesian parameter estimation in stochastic models of multicellular clocks

We investigate a stochastic version of the synthetic multicellular clock model proposed by Garcia-Ojalvo, Elowitz and Strogatz. By introducing dynamical noise in the model and assuming that the partial observations of the system can be contaminated by additive noise, we enable a principled mechanism to represent experimental uncertainties in the synthesis of the multicellular system and pave the way for the design of probabilistic methods for the estimation of any unknowns in the model. Within this setup, we investigate the use of an iterative importance sampling scheme, termed nonlinear population Monte Carlo (NPMC), for the Bayesian estimation of the model parameters. The algorithm yields a stochastic approximation of the posterior probability distribution of the unknown parameters given the available data (partial and possibly noisy observations). We prove a new theoretical result for this algorithm, which indicates that the approximations converge almost surely to the actual distributions, even when the weights in the importance sampling scheme cannot be computed exactly. We also provide a detailed numerical assessment of the stochastic multicellular model and the accuracy of the proposed NPMC algorithm, including a comparison with the popular particle Metropolis-Hastings algorithm of Andrieu {\em et al.}, 2010, applied to the same model and an approximate Bayesian computation sequential Monte Carlo method introduced by Mariño {\em et al.}, 2013.

stat.CO

Effect of noise in intelligent cellular decision making

Similar to intelligent multicellular neural networks controlling human brains, even single cells surprisingly are able to make intelligent decisions to classify several external stimuli or to associate them. This happens because of the fact that gene regulatory networks can perform as perceptrons, simple intelligent schemes known from studies on Artificial Intelligence. We study the role of genetic noise in intelligent decision making at the genetic level and show that noise can play a constructive role helping cells to make a proper decision. We show this using the example of a simple genetic classifier able to classify two external stimuli.

q-bio.MN

Multi-input distributed classifiers for synthetic genetic circuits

For practical construction of complex synthetic genetic networks able to perform elaborate functions it is important to have a pool of relatively simple "bio-bricks" with different functionality which can be compounded together. To complement engineering of very different existing synthetic genetic devices such as switches, oscillators or logical gates, we propose and develop here a design of synthetic multiple input distributed classifier with learning ability. Proposed classifier will be able to separate multi-input data, which are inseparable for single input classifiers. Additionally, the data classes could potentially occupy the area of any shape in the space of inputs. We study two approaches to classification, including hard and soft classification and confirm the schemes of genetic networks by analytical and numerical results.

q-bio.MN

Towards quantitative prediction of proteasomal digestion patterns of proteins

We discuss the problem of proteasomal degradation of proteins. Though proteasomes are important for all aspects of the cellular metabolism, some details of the physical mechanism of the process remain unknown. We introduce a stochastic model of the proteasomal degradation of proteins, which accounts for the protein translocation and the topology of the positioning of cleavage centers of a proteasome from first principles. For this model we develop the mathematical description based on a master-equation and techniques for reconstruction of the cleavage specificity inherent to proteins and the proteasomal translocation rates, which are a property of the proteasome specie, from mass spectroscopy data on digestion patterns. With these properties determined, one can quantitatively predict digestion patterns for new experimental set-ups. Additionally we design an experimental set-up for a synthetic polypeptide with a periodic sequence of amino acids, which enables especially reliable determination of translocation rates.

q-bio.SC