ترغب بنشر مسار تعليمي؟ اضغط هنا

Information-theoretic analysis of multivariate single - cell signaling responses using SLEMI

135   0   0.0 ( 0 )
 نشر من قبل Michal Komorowski
 تاريخ النشر 2018
  مجال البحث علم الأحياء
والبحث باللغة English




اسأل ChatGPT حول البحث

Mathematical methods of information theory constitute essential tools to describe how stimuli are encoded in activities of signaling effectors. Exploring the information-theoretic perspective, however, remains conceptually, experimentally and computationally challenging. Specifically, existing computational tools enable efficient analysis of relatively simple systems, usually with one input and output only. Moreover, their robust and readily applicable implementations are missing. Here, we propose a novel algorithm to analyze signaling data within the framework of information theory. Our approach enables robust as well as statistically and computationally efficient analysis of signaling systems with high-dimensional outputs and a large number of input values. Analysis of the NF-kB single - cell signaling responses to TNF-a uniquely reveals that the NF-kB signaling dynamics improves discrimination of high concentrations of TNF-a with a modest impact on discrimination of low concentrations. Our readily applicable R-package, SLEMI - statistical learning based estimation of mutual information, allows the approach to be used by computational biologists with only elementary knowledge of information theory.

قيم البحث

اقرأ أيضاً

Single cell responses are shaped by the geometry of signaling kinetic trajectories carved in a multidimensional space spanned by signaling protein abundances. It is however challenging to assay large number (>3) of signaling species in live-cell imag ing which makes it difficult to probe single cell signaling kinetic trajectories in large dimensions. Flow and mass cytometry techniques can measure a large number (4 - >40) of signaling species but are unable to track single cells. Thus cytometry experiments provide detailed time stamped snapshots of single cell signaling kinetics. Is it possible to use the time stamped cytometry data to reconstruct single cell signaling trajectories? Borrowing concepts of conserved and slow variables from non-equilibrium statistical physics we develop an approach to reconstruct signaling trajectories using snapshot data by creating new variables that remain invariant or vary slowly during the signaling kinetics. We apply this approach to reconstruct trajectories using snapshot data obtained from in silico simulations and live-cell imaging measurements. The use of invariants and slow variables to reconstruct trajectories provides a radically different way to track object using snapshot data. The approach is likely to have implications for solving matching problems in a wide range of disciplines.
Sensitivity analysis is an effective tool for systematically identifying specific perturbations in parameters that have significant effects on the behavior of a given biosystem, at the scale investigated. In this work, using a two-dimensional, multis cale non-small cell lung cancer (NSCLC) model, we examine the effects of perturbations in system parameters which span both molecular and cellular levels, i.e. across scales of interest. This is achieved by first linking molecular and cellular activities and then assessing the influence of parameters at the molecular level on the tumors spatio-temporal expansion rate, which serves as the output behavior at the cellular level. Overall, the algorithm operated reliably over relatively large variations of most parameters, hence confirming the robustness of the model. However, three pathway components (proteins PKC, MEK, and ERK) and eleven reaction steps were determined to be of critical importance by employing a sensitivity coefficient as an evaluation index. Each of these sensitive parameters exhibited a similar changing pattern in that a relatively larger increase or decrease in its value resulted in a lesser influence on the systems cellular performance. This study provides a novel cross-scaled approach to analyzing sensitivities of computational model parameters and proposes its application to interdisciplinary biomarker studies.
96 - Etay Ziv 2004
Exploiting recent developments in information theory, we propose, illustrate, and validate a principled information-theoretic algorithm for module discovery and resulting measure of network modularity. This measure is an order parameter (a dimensionl ess number between 0 and 1). Comparison is made to other approaches to module-discovery and to quantifying network modularity using Monte Carlo generated Erdos-like modular networks. Finally, the Network Information Bottleneck (NIB) algorithm is applied to a number of real world networks, including the social network of coauthors at the APS March Meeting 2004.
The development of single-cell technologies provides the opportunity to identify new cellular states and reconstruct novel cell-to-cell relationships. Applications range from understanding the transcriptional and epigenetic processes involved in meta zoan development to characterizing distinct cells types in heterogeneous populations like cancers or immune cells. However, analysis of the data is impeded by its unknown intrinsic biological and technical variability together with its sparseness; these factors complicate the identification of true biological signals amidst artifact and noise. Here we show that, across technologies, roughly 95% of the eigenvalues derived from each single-cell data set can be described by universal distributions predicted by Random Matrix Theory. Interestingly, 5% of the spectrum shows deviations from these distributions and present a phenomenon known as eigenvector localization, where information tightly concentrates in groups of cells. Some of the localized eigenvectors reflect underlying biological signal, and some are simply a consequence of the sparsity of single cell data; roughly 3% is artifactual. Based on the universal distributions and a technique for detecting sparsity induced localization, we present a strategy to identify the residual 2% of directions that encode biological information and thereby denoise single-cell data. We demonstrate the effectiveness of this approach by comparing with standard single-cell data analysis techniques in a variety of examples with marked cell populations.
The broad concept of emergence is instrumental in various of the most challenging open scientific questions -- yet, few quantitative theories of what constitutes emergent phenomena have been proposed. This article introduces a formal theory of causal emergence in multivariate systems, which studies the relationship between the dynamics of parts of a system and macroscopic features of interest. Our theory provides a quantitative definition of downward causation, and introduces a complementary modality of emergent behaviour -- which we refer to as causal decoupling. Moreover, the theory allows practical criteria that can be efficiently calculated in large systems, making our framework applicable in a range of scenarios of practical interest. We illustrate our findings in a number of case studies, including Conways Game of Life, Reynolds flocking model, and neural activity as measured by electrocorticography.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا