REMR: Identification of RNA Editing-mediated MiRNA Regulation in Cancers.

Dysregulation of adenosine-to-inosine (A-to-I) RNA editing has been implicated in cancer progression. However, a comprehensive understanding of how A-to-I RNA editing is incorporated into miRNA regulation to modulate gene expression in cancer remains unclear, given the lack of effective identification methods. To this end, we introduced an information theory-based algorithm named REMR to systematically identify 12,006 A-to-I RNA editing-mediated miRNA regulatory triplets (RNA editing sites, miRNAs, and genes) across ten major cancer types based on multi-omics profiling data from The Cancer Genome Atlas (TCGA). Through analyses of functional enrichment, transcriptional regulatory networks, and protein-protein interaction (PPI) networks, we showed that RNA editing-mediated miRNA regulation potentially affects critical cancer-related functions, such as apoptosis, cell cycle, drug resistance, and immunity. Furthermore, triplets can serve as biomarkers for classifying cancer subtypes with distinct prognoses or drug responses, highlighting the clinical relevance of such regulation. In addition, an online resource (http://www.jianglab.cn/REMR/) was constructed to support the convenient retrieval of our findings. In summary, our study systematically dissected the RNA editing-mediated miRNA regulations, thereby providing a valuable resource for understanding the mechanism of RNA editing as an epitranscriptomic regulator in cancer.

Gate-set evaluation metrics for closed-loop optimal control on nitrogen-vacancy center ensembles in diamond.

A recurring challenge in quantum science and technology is the precise control of their underlying dynamics that lead to the desired quantum operations, often described by a set of quantum gates. These gates can be subject to application-specific errors, leading to a dependence of their controls on the chosen circuit, the quality measure and the gate-set itself. A natural solution would be to apply quantum optimal control in an application-oriented fashion. In turn, this requires the definition of a meaningful measure of the contextual gate-set performance. Therefore, we explore and compare the applicability of quantum process tomography, linear inversion gate-set tomography, randomized linear gate-set tomography, and randomized benchmarking as measures for closed-loop quantum optimal control experiments, using a macroscopic ensemble of nitrogen-vacancy centers in diamond as a test-bed. Our work demonstrates the relative trade-offs between those measures and how to significantly enhance the gate-set performance, leading to an improvement across all investigated methods.

Limits on inferring T cell specificity from partial information.

A key challenge in molecular biology is to decipher the mapping of protein sequence to function. To perform this mapping requires the identification of sequence features most informative about function. Here, we quantify the amount of information (in bits) that T cell receptor (TCR) sequence features provide about antigen specificity. We identify informative features by their degree of conservation among antigen-specific receptors relative to null expectations. We find that TCR specificity synergistically depends on the hypervariable regions of both receptor chains, with a degree of synergy that strongly depends on the ligand. Using a coincidence-based approach to measuring information enables us to directly bound the accuracy with which TCR specificity can be predicted from partial matches to reference sequences. We anticipate that our statistical framework will be of use for developing machine learning models for TCR specificity prediction and for optimizing TCRs for cell therapies. The proposed coincidence-based information measures might find further applications in bounding the performance of pairwise classifiers in other fields.

Automated single-cell omics end-to-end framework with data-driven batch inference.

To facilitate single-cell multi-omics analysis and improve reproducibility, we present single-cell pipeline for end-to-end data integration (SPEEDI), a fully automated end-to-end framework for batch inference, data integration, and cell-type labeling. SPEEDI introduces data-driven batch inference and transforms the often heterogeneous data matrices obtained from different samples into a uniformly annotated and integrated dataset. Without requiring user input, it automatically selects parameters and executes pre-processing, sample integration, and cell-type mapping. It can also perform downstream analyses of differential signals between treatment conditions and gene functional modules. SPEEDI's data-driven batch-inference method works with widely used integration and cell-typing tools. By developing data-driven batch inference, providing full end-to-end automation, and eliminating parameter selection, SPEEDI improves reproducibility and lowers the barrier to obtaining biological insight from these valuable single-cell datasets. The SPEEDI interactive web application can be accessed at https://speedi.princeton.edu/. A record of this paper's transparent peer review process is included in the supplemental information.

An Information-Geometric Formulation of Pattern Separation and Evaluation of Existing Indices.

Pattern separation is a computational process by which dissimilar neural patterns are generated from similar input patterns. We present an information-geometric formulation of pattern separation, where a pattern separator is modeled as a family of statistical distributions on a manifold. Such a manifold maps an input (i.e., coordinates) to a probability distribution that generates firing patterns. Pattern separation occurs when small coordinate changes result in large distances between samples from the corresponding distributions. Under this formulation, we implement a two-neuron system whose probability law forms a three-dimensional manifold with mutually orthogonal coordinates representing the neurons' marginal and correlational firing rates. We use this highly controlled system to examine the behavior of spike train similarity indices commonly used in pattern separation research. We find that all indices (except scaling factor) are sensitive to relative differences in marginal firing rates, but no index adequately captures differences in spike trains that result from altering the correlation in activity between the two neurons. That is, existing pattern separation metrics appear (A) sensitive to patterns that are encoded by different neurons but (B) insensitive to patterns that differ only in relative spike timing (e.g., synchrony between neurons in the ensemble).

Inferring Dealer Networks in the Foreign Exchange Market Using Conditional Transfer Entropy: Analysis of a Central Bank Announcement.

The foreign exchange (FX) market has evolved into a complex system where locally generated information percolates through the dealer network via high-frequency interactions. Information related to major events, such as economic announcements, spreads rapidly through this network, potentially inducing volatility, liquidity disruptions, and contagion effects across financial markets. Yet, research on the mechanics of information flows in the FX market is limited. In this paper, we introduce a novel approach employing conditional transfer entropy to construct networks of information flows. Leveraging a unique, high-resolution dataset of bid and ask prices, we investigate the impact of an announcement by the European Central Bank on the information transfer within the market. During the announcement, we identify key dealers as information sources, conduits, and sinks, and, through comparison to a baseline, uncover shifts in the network topology.

Two Levels of Integrated Information Theory: From Autonomous Systems to Conscious Life.

Integrated Information Theory (IIT) is one of the most prominent candidates for a theory of consciousness, although it has received much criticism for trying to live up to expectations. Based on the relevance of three issues generalized from the developments of IITs, we have summarized the main ideas of IIT into two levels. At the second level, IIT claims to be strictly anchoring consciousness, but the first level on which it is based is more about autonomous systems or systems that have reached some other critical complexity. In this paper, we argue that the clear gap between the two levels of explanation of IIT has led to these criticisms and that its panpsychist tendency plays a crucial role in this. We suggest that the problems of IIT are far from being "pseudoscience", and by adding more necessary elements, when the first level is combined with the second level, IIT can genuinely move toward an appropriate theory of consciousness that can provide necessary and sufficient interpretations.

Bidirectional Decoupled Distillation for Heterogeneous Federated Learning.

Federated learning enables multiple devices to collaboratively train a high-performance model on the central server while keeping their data on the devices themselves. However, due to the significant variability in data distribution across devices, the aggregated global model's optimization direction may differ from that of the local models, making the clients lose their personality. To address this challenge, we propose a Bidirectional Decoupled Distillation For Heterogeneous Federated Learning (BDD-HFL) approach, which incorporates an additional private model within each local client. This design enables mutual knowledge exchange between the private and local models in a bidirectional manner. Specifically, previous one-way federated distillation methods mainly focused on learning features from the target class, which limits their ability to distill features from non-target classes and hinders the convergence of local models. To solve this limitation, we decompose the network output into target and non-target class logits and distill them separately using a joint optimization of cross-entropy and decoupled relative-entropy loss. We evaluate the effectiveness of BDD-HFL through extensive experiments on three benchmarks under IID, Non-IID, and unbalanced data distribution scenarios. Our results show that BDD-HFL outperforms state-of-the-art federated distillation methods across five baselines, achieving at most 3% improvement in average classification accuracy on the CIFAR-10, CIFAR-100, and MNIST datasets. The experiments demonstrate the superiority and generalization capability of BDD-HFL in addressing personalization challenges in federated learning.

Probing Asymmetric Interactions with Time-Separated Mutual Information: A Case Study Using Golden Shiners.

Leader-follower modalities and other asymmetric interactions that drive the collective motion of organisms are often quantified using information theory metrics like transfer or causation entropy. These metrics are difficult to accurately evaluate without a much larger number of data than is typically available from a time series of animal trajectories collected in the field or from experiments. In this paper, we use a generalized leader-follower model to argue that the time-separated mutual information between two organism positions can serve as an alternative metric for capturing asymmetric correlations that is much less data intensive and more accurately estimated by popular k-nearest neighbor algorithms than transfer entropy. Our model predicts a local maximum of this mutual information at a time separation value corresponding to the fundamental reaction timescale of the follower organism. We confirm this prediction by analyzing time series trajectories recorded for a pair of golden shiner fish circling an annular tank.

Assessing the Operational Characteristics of the Individual Causal Association as a Metric of Surrogacy in the Binary Continuous Setting.

In a causal inference framework, a new metric has been proposed to quantify surrogacy for a continuous putative surrogate and a binary true endpoint, based on information theory. The proposed metric, termed the individual causal association (ICA), was quantified using a joint causal inference model for the corresponding potential outcomes. Due to the non-identifiability inherent in this type of models, a sensitivity analysis was introduced to study the behavior of the ICA as a function of the non-identifiable parameters characterizing the aforementioned model. In this scenario, to reduce uncertainty, several plausible yet untestable assumptions like monotonicity, independence, conditional independence or homogeneous variance-covariance, are often incorporated into the analysis. We assess the robustness of the methodology regarding these simplifying assumptions via simulation. The practical implications of the findings are demonstrated in the analysis of a randomized clinical trial evaluating an inactivated quadrivalent influenza vaccine.

Dynamic predictability and activity-location contexts in human mobility.

Human travelling behaviours are markedly regular, to a large extent predictable, and mostly driven by biological necessities and social constructs. Not surprisingly, such predictability is influenced by an array of factors ranging in scale from individual preferences and choices, through social groups and households, all the way to the global scale, such as mobility restrictions in response to external shocks such as pandemics. In this work, we explore how temporal, activity and location variations in individual-level mobility-referred to as predictability states-carry a large degree of information regarding the nature of mobility regularities at the population level. Our findings indicate the existence of contextual and activity signatures in predictability states, suggesting the potential for a more nuanced approach to estimating both short-term and higher-order mobility predictions. The existence of location contexts, in particular, serves as a parsimonious estimator for predictability patterns even in the case of low resolution and missing data.

Assigning credit where it is due: an information content score to capture the clinical value of multiplexed assays of variant effect.

BACKGROUND: A variant can be pathogenic or benign with relation to a human disease. Current classification categories from benign to pathogenic reflect a probabilistic summary of the current understanding. A primary metric of clinical utility for multiplexed assays of variant effect (MAVE) is the number of variants that can be reclassified from uncertain significance (VUS). However, a gap in this measure of utility is that it underrepresents the information gained from MAVEs. The aim of this study was to develop an improved quantification metric for MAVE utility. We propose adopting an information content approach that includes data that does not reclassify variants will better reflect true information gain. We adopted an information content approach to evaluate the information gain, in bits, for MAVEs of BRCA1, PTEN, and TP53. Here, one bit represents the amount of information required to completely classify a single variant starting from no information. RESULTS: BRCA1 MAVEs produced a total of 831.2 bits of information, 6.58% of the total missense information in BRCA1 and a 22-fold increase over the information that only contributed to VUS reclassification. PTEN MAVEs produced 2059.6 bits of information which represents 32.8% of the total missense information in PTEN and an 85-fold increase over the information that contributed to VUS reclassification. TP53 MAVEs produced 277.8 bits of information which represents 6.22% of the total missense information in TP53 and a 3.5-fold increase over the information that contributed to VUS reclassification. CONCLUSIONS: An information content approach will more accurately portray information gained through MAVE mapping efforts than by counting the number of variants reclassified. This information content approach may also help define the impact of guideline changes that modify the information definitions used to classify groups of variants.

Research on Division of Labor Decision and System Stability of Swarm Robots Based on Mutual Information.

In rational decision-making processes, the information interaction among individual robots is a critical factor influencing system stability. We establish a game-theoretic model based on mutual information to address division of labor decision-making and stability issues arising from differential information interaction among swarm robots. Firstly, a mutual information model is employed to measure the information interaction among robots and analyze its influence on the behavior of individual robots. Secondly, employing the Cournot model and the Stackelberg model, we model the diverse decision-making behaviors of swarm robots influenced by discrepancies in mutual information. The intricate decision dynamics exhibited by the system under the disparity mutual information values during the game process, along with the stability of Nash equilibrium points, are analyzed. Finally, dynamic complexity simulations of the game models are simulated under the disparity mutual information values: (1) When ν1 of the game model varies within a certain range, the Nash equilibrium point loses stability and enters a chaotic state. (2) As I(X;Y) increases, the decision-making pattern of robots transitions gradually from the Cournot game to the Stackelberg game. Concurrently, the sensitivity of swarm robotics systems to changes in decision parameter decreases, reducing the likelihood of the system entering a chaotic state.

Inferring the roles of individuals in collective systems using information-theoretic measures of influence.

In collective systems, influence of individuals can permeate an entire group through indirect interactionscom-plicating any scheme to understand individual roles from observations. A typical approach to understand an individuals influence on another involves consideration of confounding factors, for example, by conditioning on other individuals outside of the pair. This becomes unfeasible in many cases as the number of individuals increases. In this article, we review some of the unforeseen problems that arise in understanding individual influence in a collective such as single cells, as well as some of the recent works which address these issues using tools from information theory.

An Attacker-Defender Game Model with Constrained Strategies.

Recently, research interest in the field of infrastructure attack and defense scenarios has increased. Numerous methods have been proposed for studying strategy interactions that combine complex network theory and game theory. However, the unavoidable effect of constrained strategies in complex situations has not been considered in previous studies. This study introduces a novel approach to analyzing these interactions by including the effects of constrained strategies, a factor often neglected in traditional analyses. First, we introduce the rule of constraints on strategies, which depends on the average distance between selected nodes. As the average distance increases, the probability of choosing the corresponding strategy decreases. Second, we establish an attacker-defender game model with constrained strategies based on the above rule and using information theory to evaluate the uncertainty of these strategies. Finally, we present a method for solving this problem and conduct experiments based on a target network. The results highlight the unique characteristics of the Nash equilibrium when setting constraints, as these constraints influence decision makers' Nash equilibria. When considering the constrained strategies, both the attacker and the defender tend to select strategies with lower average distances. The effect of the constraints on their strategies becomes less apparent as the number of attackable or defendable nodes increases. This research advances the field by introducing a novel framework for examining strategic interactions in infrastructure defense and attack scenarios. By incorporating strategy constraints, our work offers a new perspective on the critical area of infrastructure security.

Understanding Higher-Order Interactions in Information Space.

Methods used in topological data analysis naturally capture higher-order interactions in point cloud data embedded in a metric space. This methodology was recently extended to data living in an information space, by which we mean a space measured with an information theoretical distance. One such setting is a finite collection of discrete probability distributions embedded in the probability simplex measured with the relative entropy (Kullback-Leibler divergence). More generally, one can work with a Bregman divergence parameterized by a different notion of entropy. While theoretical algorithms exist for this setup, there is a paucity of implementations for exploring and comparing geometric-topological properties of various information spaces. The interest of this work is therefore twofold. First, we propose the first robust algorithms and software for geometric and topological data analysis in information space. Perhaps surprisingly, despite working with Bregman divergences, our design reuses robust libraries for the Euclidean case. Second, using the new software, we take the first steps towards understanding the geometric-topological structure of these spaces. In particular, we compare them with the more familiar spaces equipped with the Euclidean and Fisher metrics.

Contrast Information Dynamics: A Novel Information Measure for Cognitive Modelling.

We present contrast information, a novel application of some specific cases of relative entropy, designed to be useful for the cognitive modelling of the sequential perception of continuous signals. We explain the relevance of entropy in the cognitive modelling of sequential phenomena such as music and language. Then, as a first step to demonstrating the utility of constrast information for this purpose, we empirically show that its discrete case correlates well with existing successful cognitive models in the literature. We explain some interesting properties of constrast information. Finally, we propose future work toward a cognitive architecture that uses it.

Conscious Causality, Observer-Observed Simultaneity, and the Problem of Time for Integrated Information Theory.

Without proven causal power, consciousness cannot be integrated with physics except as an epiphenomenon, hence the term 'hard problem'. Integrated Information Theory (IIT) side-steps the issue by stating that subjective experience must be identical to informational physical structures whose cause-and-effect power is greater than the sum of their parts. But the focus on spatially oriented structures rather than events in time introduces a deep conceptual flaw throughout its entire structure, including the measure of integrated information, known as Φ (phi). However, the problem can be corrected by incorporating the temporal feature of consciousness responsible for the hard problem, which can ultimately resolve it, namely, that experiencer and experienced are not separated in time but exist simultaneously. Simultaneous causation is not possible in physics, hence the hard problem, and yet it can be proven deductively that consciousness does have causal power because of this phenomenological simultaneity. Experiencing presence makes some facts logically possible that would otherwise be illogical. Bypassing the hard problem has caused much of the criticism that IIT has attracted, but by returning to its roots in complexity theory, it can repurpose its model to measure causal connections that are temporally rather than spatially related.

Response inhibition in premotor cortex corresponds to a complex reshuffle of the mesoscopic information network.

Recent studies have explored functional and effective neural networks in animal models; however, the dynamics of information propagation among functional modules under cognitive control remain largely unknown. Here, we addressed the issue using transfer entropy and graph theory methods on mesoscopic neural activities recorded in the dorsal premotor cortex of rhesus monkeys. We focused our study on the decision time of a Stop-signal task, looking for patterns in the network configuration that could influence motor plan maturation when the Stop signal is provided. When comparing trials with successful inhibition to those with generated movement, the nodes of the network resulted organized into four clusters, hierarchically arranged, and distinctly involved in information transfer. Interestingly, the hierarchies and the strength of information transmission between clusters varied throughout the task, distinguishing between generated movements and canceled ones and corresponding to measurable levels of network complexity. Our results suggest a putative mechanism for motor inhibition in premotor cortex: a topological reshuffle of the information exchanged among ensembles of neurons.

In this study, we investigated the dynamics of information transfer among functionally identified neural modules during cognitive motor control. Our focus was on mesoscopic neural activities in the dorsal premotor cortex of rhesus monkeys engaged in a Stop-signal task. Leveraging multivariate transfer entropy and graph theory, we uncovered insights on how behavioral control shapes the topology of information transmission in a local brain network. Task phases modulated the strength and hierarchy of information exchange between modules, revealing the nuanced interplay between neural populations during generated and canceled movements. Notably, during successful inhibition, the network displayed a distinctive configuration, unveiling a novel mechanism for motor inhibition in the premotor cortex: a topological reshuffle of information among neuronal ensembles.

Thompson Sampling for Stochastic Bandits with Noisy Contexts: An Information-Theoretic Regret Analysis.

We study stochastic linear contextual bandits (CB) where the agent observes a noisy version of the true context through a noise channel with unknown channel parameters. Our objective is to design an action policy that can "approximate" that of a Bayesian oracle that has access to the reward model and the noise channel parameter. We introduce a modified Thompson sampling algorithm and analyze its Bayesian cumulative regret with respect to the oracle action policy via information-theoretic tools. For Gaussian bandits with Gaussian context noise, our information-theoretic analysis shows that under certain conditions on the prior variance, the Bayesian cumulative regret scales as O˜(mT), where m is the dimension of the feature vector and T is the time horizon. We also consider the problem setting where the agent observes the true context with some delay after receiving the reward, and show that delayed true contexts lead to lower regret. Finally, we empirically demonstrate the performance of the proposed algorithms against baselines.