Prediction of Time Series Gene Expression and Structural Analysis of Gene Regulatory Networks Using Recurrent Neural Networks

Methods for time series prediction and classification of gene regulatory networks (GRNs) from gene expression data have been treated separately so far. The recent emergence of attention-based recurrent neural network (RNN) models boosted the interpretability of RNN parameters, making them appealing for the understanding of gene interactions. In this work, we generated synthetic time series gene expression data from a range of archetypal GRNs and we relied on a dual attention RNN to predict the gene temporal dynamics. We show that the prediction is extremely accurate for GRNs with different architectures. Next, we focused on the attention mechanism of the RNN and, using tools from graph theory, we found that its graph properties allow one to hierarchically distinguish different architectures of the GRN. We show that the GRN responded differently to the addition of noise in the prediction by the RNN and we related the noise response to the analysis of the attention mechanism. In conclusion, this work provides a way to understand and exploit the attention mechanism of RNNs and it paves the way to RNN-based methods for time series prediction and inference of GRNs from gene expression data.     

Information Flow in Biological Networks for Color Vision

Biological neural networks for color vision (also known as color appearance models) consist of a cascade of linear + nonlinear layers that modify the linear measurements at the retinal photo-receptors leading to an internal (nonlinear) representation of color that correlates with psychophysical experience. The basic layers of these networks include: (1) chromatic adaptation (normalization of the mean and covariance of the color manifold); (2) change to opponent color channels (PCA-like rotation in the color space); and (3) saturating nonlinearities to obtain perceptually Euclidean color representations (similar to dimension-wise equalization). The Efficient Coding Hypothesis argues that these transforms should emerge from information-theoretic goals. In case this hypothesis holds in color vision, the question is what is the coding gain due to the different layers of the color appearance networks? In this work, a representative family of color appearance models is analyzed in terms of how the redundancy among the chromatic components is modified along the network and how much information is transferred from the input data to the noisy response. The proposed analysis is performed using data and methods that were not available before: (1) new colorimetrically calibrated scenes in different CIE illuminations for the proper evaluation of chromatic adaptation; and (2) new statistical tools to estimate (multivariate) information-theoretic quantities between multidimensional sets based on Gaussianization. The results confirm that the efficient coding hypothesis holds for current color vision models, and identify the psychophysical mechanisms critically responsible for gains in information transference: opponent channels and their nonlinear nature are more important than chromatic adaptation at the retina.     

A Family of Fitness Landscapes Modeled through Gene Regulatory Networks

Fitness landscapes are a powerful metaphor for understanding the evolution of biological systems. These landscapes describe how genotypes are connected to each other through mutation and related through fitness. Empirical studies of fitness landscapes have increasingly revealed conserved topographical features across diverse taxa, e.g., the accessibility of genotypes and “ruggedness”. As a result, theoretical studies are needed to investigate how evolution proceeds on fitness landscapes with such conserved features. Here, we develop and study a model of evolution on fitness landscapes using the lens of Gene Regulatory Networks (GRNs), where the regulatory products are computed from multiple genes and collectively treated as phenotypes. With the assumption that regulation is a binary process, we prove the existence of empirically observed, topographical features such as accessibility and connectivity. We further show that these results hold across arbitrary fitness functions and that a trade-off between accessibility and ruggedness need not exist. Then, using graph theory and a coarse-graining approach, we deduce a mesoscopic structure underlying GRN fitness landscapes where the information necessary to predict a population’s evolutionary trajectory is retained with minimal complexity. Using this coarse-graining, we develop a bottom-up algorithm to construct such mesoscopic backbones, which does not require computing the genotype network and is therefore far more efficient than brute-force approaches. Altogether, this work provides mathematical results of high-dimensional fitness landscapes and a path toward connecting theory to empirical studies.     

Multiscale Information Propagation in Emergent Functional Networks

Complex biological systems consist of large numbers of interconnected units, characterized by emergent properties such as collective computation. In spite of all the progress in the last decade, we still lack a deep understanding of how these properties arise from the coupling between the structure and dynamics. Here, we introduce the multiscale emergent functional state, which can be represented as a network where links encode the flow exchange between the nodes, calculated using diffusion processes on top of the network. We analyze the emergent functional state to study the distribution of the flow among components of 92 fungal networks, identifying their functional modules at different scales and, more importantly, demonstrating the importance of functional modules for the information content of networks, quantified in terms of network spectral entropy. Our results suggest that the topological complexity of fungal networks guarantees the existence of functional modules at different scales keeping the information entropy, and functional diversity, high.     

Algorithmic Information Distortions in Node-Aligned and Node-Unaligned Multidimensional Networks

In this article, we investigate limitations of importing methods based on algorithmic information theory from monoplex networks into multidimensional networks (such as multilayer networks) that have a large number of extra dimensions (i.e., aspects). In the worst-case scenario, it has been previously shown that node-aligned multidimensional networks with non-uniform multidimensional spaces can display exponentially larger algorithmic information (or lossless compressibility) distortions with respect to their isomorphic monoplex networks, so that these distortions grow at least linearly with the number of extra dimensions. In the present article, we demonstrate that node-unaligned multidimensional networks, either with uniform or non-uniform multidimensional spaces, can also display exponentially larger algorithmic information distortions with respect to their isomorphic monoplex networks. However, unlike the node-aligned non-uniform case studied in previous work, these distortions in the node-unaligned case grow at least exponentially with the number of extra dimensions. On the other hand, for node-aligned multidimensional networks with uniform multidimensional spaces, we demonstrate that any distortion can only grow up to a logarithmic order of the number of extra dimensions. Thus, these results establish that isomorphisms between finite multidimensional networks and finite monoplex networks do not preserve algorithmic information in general and highlight that the algorithmic information of the multidimensional space itself needs to be taken into account in multidimensional network complexity analysis.     

Fluctuation Resonance of Feed Forward Loops in Gene Regulatory Networks

应用化学主方程和线性涨落近似方法,重点研究了前馈环路(FFL)对外界输入弱信号的响应,特别考察了它的涨落共振现象．研究发现Z基因的FR行为很大程度上依赖于FFL的协同性：协同FFL中Z的FR曲线呈明显的单峰,而非协同FFL中该曲线出现明显双峰．由于振荡信号常常在实际应用中用来探测网络的调控结构,因此可以利用涨落共振曲线的定性差别来区分FFL网络的性能．     

Stability of Gene Regulatory Networks Modeled by Generalized Proportional Caputo Fractional Differential Equations

A model of gene regulatory networks with generalized proportional Caputo fractional derivatives is set up, and stability properties are studied. Initially, some properties of absolute value Lyapunov functions and quadratic Lyapunov functions are discussed, and also, their application to fractional order systems and the advantage of quadratic functions are pointed out. The equilibrium of the generalized proportional Caputo fractional model and its generalized exponential stability are defined, and sufficient conditions for the generalized exponential stability and asymptotic stability of the equilibrium are obtained. As a special case, the stability of the equilibrium of the Caputo fractional model is discussed. Several examples are provided to illustrate our theoretical results and the influence of the type of fractional derivative on the stability behavior of the equilibrium.     

Information Fragmentation,Encryption and Information Flow in Complex Biological Networks

Assessing where and how information is stored in biological networks (such as neuronal and genetic networks) is a central task both in neuroscience and in molecular genetics, but most available tools focus on the network’s structure as opposed to its function. Here, we introduce a new information-theoretic tool—information fragmentation analysis—that, given full phenotypic data, allows us to localize information in complex networks, determine how fragmented (across multiple nodes of the network) the information is, and assess the level of encryption of that information. Using information fragmentation matrices we can also create information flow graphs that illustrate how information propagates through these networks. We illustrate the use of this tool by analyzing how artificial brains that evolved in silico solve particular tasks, and show how information fragmentation analysis provides deeper insights into how these brains process information and “think”. The measures of information fragmentation and encryption that result from our methods also quantify complexity of information processing in these networks and how this processing complexity differs between primary exposure to sensory data (early in the lifetime) and later routine processing.     

Evaluating the Learning Procedure of CNNs through a Sequence of Prognostic Tests Utilising Information Theoretical Measures

Deep learning has proven to be an important element of modern data processing technology, which has found its application in many areas such as multimodal sensor data processing and understanding, data generation and anomaly detection. While the use of deep learning is booming in many real-world tasks, the internal processes of how it draws results is still uncertain. Understanding the data processing pathways within a deep neural network is important for transparency and better resource utilisation. In this paper, a method utilising information theoretic measures is used to reveal the typical learning patterns of convolutional neural networks, which are commonly used for image processing tasks. For this purpose, training samples, true labels and estimated labels are considered to be random variables. The mutual information and conditional entropy between these variables are then studied using information theoretical measures. This paper shows that more convolutional layers in the network improve its learning and unnecessarily higher numbers of convolutional layers do not improve the learning any further. The number of convolutional layers that need to be added to a neural network to gain the desired learning level can be determined with the help of theoretic information quantities including entropy, inequality and mutual information among the inputs to the network. The kernel size of convolutional layers only affects the learning speed of the network. This study also shows that where the dropout layer is applied to has no significant effects on the learning of networks with a lower dropout rate, and it is better placed immediately after the last convolutional layer with higher dropout rates.     

Neural Estimator of Information for Time-Series Data with Dependency

Novel approaches to estimate information measures using neural networks are well-celebrated in recent years both in the information theory and machine learning communities. These neural-based estimators are shown to converge to the true values when estimating mutual information and conditional mutual information using independent samples. However, if the samples in the dataset are not independent, the consistency of these estimators requires further investigation. This is of particular interest for a more complex measure such as the directed information, which is pivotal in characterizing causality and is meaningful over time-dependent variables. The extension of the convergence proof for such cases is not trivial and demands further assumptions on the data. In this paper, we show that our neural estimator for conditional mutual information is consistent when the dataset is generated with samples of a stationary and ergodic source. In other words, we show that our information estimator using neural networks converges asymptotically to the true value with probability one. Besides universal functional approximation of neural networks, a core lemma to show the convergence is Birkhoff’s ergodic theorem. Additionally, we use the technique to estimate directed information and demonstrate the effectiveness of our approach in simulations.     

基于BP神经网络的多传感器信息融合研究

BP网络是应用最广的一种人工神经网络,将BP神经网络应用到压力检测领域的温度等非线性补偿,具有重要的实用价值,对压力检测精度的改进效果显著。从传感器信息融合的角度看,神经网络就是一个融合系统。通过对神经网络基本理论的阐述,针对研究对象将BP神经网络原理与多传感器信息融合技术有机集合起来,提出了基于BP神经网络的二传感器信息融合模型及改进算法,建立了BP神经网络训练标准样本库,并对该网络模型进行主要技术指标的测试和仿真工作,测试结果表明构建的模型及其改进算法能很好地满足了高精度压力检测仪的指标要求。     

Critical Comparison of MaxCal and Other Stochastic Modeling Approaches in Analysis of Gene Networks

Learning the underlying details of a gene network with feedback is critical in designing new synthetic circuits. Yet, quantitative characterization of these circuits remains limited. This is due to the fact that experiments can only measure partial information from which the details of the circuit must be inferred. One potentially useful avenue is to harness hidden information from single-cell stochastic gene expression time trajectories measured for long periods of time—recorded at frequent intervals—over multiple cells. This raises the feasibility vs. accuracy dilemma while deciding between different models of mining these stochastic trajectories. We demonstrate that inference based on the Maximum Caliber (MaxCal) principle is the method of choice by critically evaluating its computational efficiency and accuracy against two other typical modeling approaches: (i) a detailed model (DM) with explicit consideration of multiple molecules including protein-promoter interaction, and (ii) a coarse-grain model (CGM) using Hill type functions to model feedback. MaxCal provides a reasonably accurate model while being significantly more computationally efficient than DM and CGM. Furthermore, MaxCal requires minimal assumptions since it is a top-down approach and allows systematic model improvement by including constraints of higher order, in contrast to traditional bottom-up approaches that require more parameters or ad hoc assumptions. Thus, based on efficiency, accuracy, and ability to build minimal models, we propose MaxCal as a superior alternative to traditional approaches (DM, CGM) when inferring underlying details of gene circuits with feedback from limited data.     

Clarifying How Degree Entropies and Degree-Degree Correlations Relate to Network Robustness

It is often claimed that the entropy of a network’s degree distribution is a proxy for its robustness. Here, we clarify the link between degree distribution entropy and giant component robustness to node removal by showing that the former merely sets a lower bound to the latter for randomly configured networks when no other network characteristics are specified. Furthermore, we show that, for networks of fixed expected degree that follow degree distributions of the same form, the degree distribution entropy is not indicative of robustness. By contrast, we show that the remaining degree entropy and robustness have a positive monotonic relationship and give an analytic expression for the remaining degree entropy of the log-normal distribution. We also show that degree-degree correlations are not by themselves indicative of a network’s robustness for real networks. We propose an adjustment to how mutual information is measured which better encapsulates structural properties related to robustness.     

Identifying Influential Nodes in Complex Networks Based on Multiple Local Attributes and Information Entropy

Identifying influential nodes in complex networks has attracted the attention of many researchers in recent years. However, due to the high time complexity, methods based on global attributes have become unsuitable for large-scale complex networks. In addition, compared with methods considering only a single attribute, considering multiple attributes can enhance the performance of the method used. Therefore, this paper proposes a new multiple local attributes-weighted centrality (LWC) based on information entropy, combining degree and clustering coefficient; both one-step and two-step neighborhood information are considered for evaluating the influence of nodes and identifying influential nodes in complex networks. Firstly, the influence of a node in a complex network is divided into direct influence and indirect influence. The degree and clustering coefficient are selected as direct influence measures. Secondly, based on the two direct influence measures, we define two indirect influence measures: two-hop degree and two-hop clustering coefficient. Then, the information entropy is used to weight the above four influence measures, and the LWC of each node is obtained by calculating the weighted sum of these measures. Finally, all the nodes are ranked based on the value of the LWC, and the influential nodes can be identified. The proposed LWC method is applied to identify influential nodes in four real-world networks and is compared with five well-known methods. The experimental results demonstrate the good performance of the proposed method on discrimination capability and accuracy.     

增长及非增长无标度网络的成因解析

分析两类无标度网络的形成原因,提出一个无标度网络演化模型并进行一系列数值实验.基于分析和实验得到推论:只要保持足够低的网络密度,通过基于度的偏好连接就可形成长期稳定的无标度网络.规模增长和点边增删既是客观存在,又起到了控制网络密度的作用,足够低的网络密度和基于度的偏好连接是所有无标度网络共同的必要条件.推论可同时解释增长和非增长无标度网络的形成原因.研究结果有助于理解各种真实无标度网络和建立相应的模型.     

Information Theory for Agents in Artificial Intelligence,Psychology, and Economics

This review looks at some of the central relationships between artificial intelligence, psychology, and economics through the lens of information theory, specifically focusing on formal models of decision-theory. In doing so we look at a particular approach that each field has adopted and how information theory has informed the development of the ideas of each field. A key theme is expected utility theory, its connection to information theory, the Bayesian approach to decision-making and forms of (bounded) rationality. What emerges from this review is a broadly unified formal perspective derived from three very different starting points that reflect the unique principles of each field. Each of the three approaches reviewed can, in principle at least, be implemented in a computational model in such a way that, with sufficient computational power, they could be compared with human abilities in complex tasks. However, a central critique that can be applied to all three approaches was first put forward by Savage in The Foundations of Statistics and recently brought to the fore by the economist Binmore: Bayesian approaches to decision-making work in what Savage called ‘small worlds’ but cannot work in ‘large worlds’. This point, in various different guises, is central to some of the current debates about the power of artificial intelligence and its relationship to human-like learning and decision-making. Recent work on artificial intelligence has gone some way to bridging this gap but significant questions remain to be answered in all three fields in order to make progress in producing realistic models of human decision-making in the real world in which we live in.     

Thermodynamics of Vacancies and Impurities at Grain Boundaries

The thermodynamics of vacancy and impurity adsorption at interfaces and grain boundaries (GBs) in solids is considered. Theoretical expressions are derived for the GB/interface free energy change caused by various levels of vacancy or impurity adsorption. This information is used to predict the behavior of vacancies at interfaces and GBs in a stress gradient and to forecast the effect of impurities on GB fracture strength. The latter predictions provide an interpretation of intergranular fracture behavior in terms of impurity adsorption and GB structural parameters such as GB width and value.     

Mutual Information and Relative Entropy of Sequential Effect Algebras

In this paper, we introduce and investigate the mutual information and relative entropy on the sequential effect algebra, we also give a comparison of these mutual information and relative entropy with the classical ones by the venn diagrams. Finally, a nice example shows that the entropies of sequential effect algebra depend extremely on the order of its sequential product.     

Use of Average Mutual Information and Derived Measures to Find Coding Regions

One of the important steps in the annotation of genomes is the identification of regions in the genome which code for proteins. One of the tools used by most annotation approaches is the use of signals extracted from genomic regions that can be used to identify whether the region is a protein coding region. Motivated by the fact that these regions are information bearing structures we propose signals based on measures motivated by the average mutual information for use in this task. We show that these signals can be used to identify coding and noncoding sequences with high accuracy. We also show that these signals are robust across species, phyla, and kingdom and can, therefore, be used in species agnostic genome annotation algorithms for identifying protein coding regions. These in turn could be used for gene identification.     

Mutual Information and Relative Entropy of Sequential Effect Algebras

In this paper, we introduce and investigate the mutual information and relative entropy on the sequential effect algebra, we also give a comparison of these mutual information and relative entropy with the classical ones by the venn diagrams. Finally, a nice example shows that the entropies of sequential effect algebra depend extremely on the order of its sequential product.