Pyfectious: An individual-level simulator to discover optimal containment policies for epidemic diseases.

Simulating the spread of infectious diseases in human communities is critical for predicting the trajectory of an epidemic and verifying various policies to control the devastating impacts of the outbreak. Many existing simulators are based on compartment models that divide people into a few subsets and simulate the dynamics among those subsets using hypothesized differential equations. However, these models lack the requisite granularity to study the effect of intelligent policies that influence every individual in a particular way. In this work, we introduce a simulator software capable of modeling a population structure and controlling the disease's propagation at an individualistic level. In order to estimate the confidence of the conclusions drawn from the simulator, we employ a comprehensive probabilistic approach where the entire population is constructed as a hierarchical random variable. This approach makes the inferred conclusions more robust against sampling artifacts and gives confidence bounds for decisions based on the simulation results. To showcase potential applications, the simulator parameters are set based on the formal statistics of the COVID-19 pandemic, and the outcome of a wide range of control measures is investigated. Furthermore, the simulator is used as the environment of a reinforcement learning problem to find the optimal policies to control the pandemic. The obtained experimental results indicate the simulator's adaptability and capacity in making sound predictions and a successful policy derivation example based on real-world data. As an exemplary application, our results show that the proposed policy discovery method can lead to control measures that produce significantly fewer infected individuals in the population and protect the health system against saturation.

ResMiCo: Increasing the quality of metagenome-assembled genomes with deep learning.

The number of published metagenome assemblies is rapidly growing due to advances in sequencing technologies. However, sequencing errors, variable coverage, repetitive genomic regions, and other factors can produce misassemblies, which are challenging to detect for taxonomically novel genomic data. Assembly errors can affect all downstream analyses of the assemblies. Accuracy for the state of the art in reference-free misassembly prediction does not exceed an AUPRC of 0.57, and it is not clear how well these models generalize to real-world data. Here, we present the Residual neural network for Misassembled Contig identification (ResMiCo), a deep learning approach for reference-free identification of misassembled contigs. To develop ResMiCo, we first generated a training dataset of unprecedented size and complexity that can be used for further benchmarking and developments in the field. Through rigorous validation, we show that ResMiCo is substantially more accurate than the state of the art, and the model is robust to novel taxonomic diversity and varying assembly methods. ResMiCo estimated 7% misassembled contigs per metagenome across multiple real-world datasets. We demonstrate how ResMiCo can be used to optimize metagenome assembly hyperparameters to improve accuracy, instead of optimizing solely for contiguity. The accuracy, robustness, and ease-of-use of ResMiCo make the tool suitable for general quality control of metagenome assemblies and assembly methodology optimization.

Neural Importance Sampling for Rapid and Reliable Gravitational-Wave Inference.

We combine amortized neural posterior estimation with importance sampling for fast and accurate gravitational-wave inference. We first generate a rapid proposal for the Bayesian posterior using neural networks, and then attach importance weights based on the underlying likelihood and prior. This provides (1) a corrected posterior free from network inaccuracies, (2) a performance diagnostic (the sample efficiency) for assessing the proposal and identifying failure cases, and (3) an unbiased estimate of the Bayesian evidence. By establishing this independent verification and correction mechanism we address some of the most frequent criticisms against deep learning for scientific inference. We carry out a large study analyzing 42 binary black hole mergers observed by LIGO and Virgo with the SEOBNRv4PHM and IMRPhenomXPHM waveform models. This shows a median sample efficiency of ≈10% (2 orders of magnitude better than standard samplers) as well as a tenfold reduction in the statistical uncertainty in the log evidence. Given these advantages, we expect a significant impact on gravitational-wave inference, and for this approach to serve as a paradigm for harnessing deep learning methods in scientific applications.

Kernel-Based Independence Tests for Causal Structure Learning on Functional Data.

Measurements of systems taken along a continuous functional dimension, such as time or space, are ubiquitous in many fields, from the physical and biological sciences to economics and engineering. Such measurements can be viewed as realisations of an underlying smooth process sampled over the continuum. However, traditional methods for independence testing and causal learning are not directly applicable to such data, as they do not take into account the dependence along the functional dimension. By using specifically designed kernels, we introduce statistical tests for bivariate, joint, and conditional independence for functional variables. Our method not only extends the applicability to functional data of the Hilbert-Schmidt independence criterion (hsic) and its d-variate version (d-hsic), but also allows us to introduce a test for conditional independence by defining a novel statistic for the conditional permutation test (cpt) based on the Hilbert-Schmidt conditional independence criterion (hscic), with optimised regularisation strength estimated through an evaluation rejection rate. Our empirical results of the size and power of these tests on synthetic functional data show good performance, and we then exemplify their application to several constraint- and regression-based causal structure learning problems, including both synthetic examples and real socioeconomic data.

Enhancing human learning via spaced repetition optimization.

Spaced repetition is a technique for efficient memorization which uses repeated review of content following a schedule determined by a spaced repetition algorithm to improve long-term retention. However, current spaced repetition algorithms are simple rule-based heuristics with a few hard-coded parameters. Here, we introduce a flexible representation of spaced repetition using the framework of marked temporal point processes and then address the design of spaced repetition algorithms with provable guarantees as an optimal control problem for stochastic differential equations with jumps. For two well-known human memory models, we show that, if the learner aims to maximize recall probability of the content to be learned subject to a cost on the reviewing frequency, the optimal reviewing schedule is given by the recall probability itself. As a result, we can then develop a simple, scalable online spaced repetition algorithm, MEMORIZE, to determine the optimal reviewing times. We perform a large-scale natural experiment using data from Duolingo, a popular language-learning online platform, and show that learners who follow a reviewing schedule determined by our algorithm memorize more effectively than learners who follow alternative schedules determined by several heuristics.

DeepMAsED: evaluating the quality of metagenomic assemblies.

MOTIVATION: Methodological advances in metagenome assembly are rapidly increasing in the number of published metagenome assemblies. However, identifying misassemblies is challenging due to a lack of closely related reference genomes that can act as pseudo ground truth. Existing reference-free methods are no longer maintained, can make strong assumptions that may not hold across a diversity of research projects, and have not been validated on large-scale metagenome assemblies. RESULTS: We present DeepMAsED, a deep learning approach for identifying misassembled contigs without the need for reference genomes. Moreover, we provide an in silico pipeline for generating large-scale, realistic metagenome assemblies for comprehensive model training and testing. DeepMAsED accuracy substantially exceeds the state-of-the-art when applied to large and complex metagenome assemblies. Our model estimates a 1% contig misassembly rate in two recent large-scale metagenome assembly publications. CONCLUSIONS: DeepMAsED accurately identifies misassemblies in metagenome-assembled contigs from a broad diversity of bacteria and archaea without the need for reference genomes or strong modeling assumptions. Running DeepMAsED is straight-forward, as well as is model re-training with our dataset generation pipeline. Therefore, DeepMAsED is a flexible misassembly classifier that can be applied to a wide range of metagenome assembly projects. AVAILABILITY AND IMPLEMENTATION: DeepMAsED is available from GitHub at https://github.com/leylabmpi/DeepMAsED. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Real-Time Gravitational Wave Science with Neural Posterior Estimation.

We demonstrate unprecedented accuracy for rapid gravitational wave parameter estimation with deep learning. Using neural networks as surrogates for Bayesian posterior distributions, we analyze eight gravitational wave events from the first LIGO-Virgo Gravitational-Wave Transient Catalog and find very close quantitative agreement with standard inference codes, but with inference times reduced from O(day) to 20 s per event. Our networks are trained using simulated data, including an estimate of the detector noise characteristics near the event. This encodes the signal and noise models within millions of neural-network parameters and enables inference for any observed data consistent with the training distribution, accounting for noise nonstationarity from event to event. Our algorithm-called "DINGO"-sets a new standard in fast and accurate inference of physical parameters of detected gravitational wave events, which should enable real-time data analysis without sacrificing accuracy.

A 32-channel multi-coil setup optimized for human brain shimming at 9.4T.

PURPOSE: A multi-coil shim setup is designed and optimized for human brain shimming. Here, the size and position of a set of square coils are optimized to improve the shim performance without increasing the number of local coils. Utilizing such a setup is especially beneficial at ultrahigh fields where B0 inhomogeneity in the human brain is more severe. METHODS: The optimization started with a symmetric arrangement of 32 independent coils. Three parameters per coil were optimized in parallel, including angular and axial positions on a cylinder surface and size of the coil, which were constrained by cylinder size, construction consideration, and amplifiers specifications. B0 maps were acquired at 9.4T in 8 healthy volunteers for use as training data. The global and dynamic shimming performance of the optimized multi-coil were compared in simulations and measurements to a symmetric design and to the scanner's second-order shim setup, respectively. RESULTS: The optimized multi-coil performs better by 14.7% based on standard deviation (SD) improvement with constrained global shimming in comparison to the symmetric positioning of the coils. Global shimming performance was comparable with a symmetric 65-channel multi-coil and full fifth-order spherical harmonic shim coils. On average, an SD of 48.4 and 31.9 Hz was achieved for in vivo measurements after global and dynamic slice-wise shimming, respectively. CONCLUSIONS: An optimized multi-coil shim setup was designed and constructed for human whole-brain shimming. Similar performance of the multi-coils with many channels can be achieved with a fewer number of channels when the coils are optimally arranged around the target.

easyGWAS: A Cloud-Based Platform for Comparing the Results of Genome-Wide Association Studies.

The ever-growing availability of high-quality genotypes for a multitude of species has enabled researchers to explore the underlying genetic architecture of complex phenotypes at an unprecedented level of detail using genome-wide association studies (GWAS). The systematic comparison of results obtained from GWAS of different traits opens up new possibilities, including the analysis of pleiotropic effects. Other advantages that result from the integration of multiple GWAS are the ability to replicate GWAS signals and to increase statistical power to detect such signals through meta-analyses. In order to facilitate the simple comparison of GWAS results, we present easyGWAS, a powerful, species-independent online resource for computing, storing, sharing, annotating, and comparing GWAS. The easyGWAS tool supports multiple species, the uploading of private genotype data and summary statistics of existing GWAS, as well as advanced methods for comparing GWAS results across different experiments and data sets in an interactive and user-friendly interface. easyGWAS is also a public data repository for GWAS data and summary statistics and already includes published data and results from several major GWAS. We demonstrate the potential of easyGWAS with a case study of the model organism Arabidopsis thaliana, using flowering and growth-related traits.

Spread-spectrum magnetic resonance imaging.

PURPOSE: A novel method for the acceleration of MRI acquisition is proposed that relies on the local modulation of magnetic fields. These local modulations provide additional spatial information for image reconstruction that is used to accelerate image acquisition. METHODS: In experiments and simulations, eight local coils connected to current amplifiers were used for rapid local magnetic field variation. Acquired and simulated data were reconstructed to quantify reconstruction errors as a function of the acceleration factor and applied modulation frequency and strength. RESULTS: Experimental results demonstrate a possible acceleration factor of 2 to 4. Simulations demonstrate the challenges and limits of this method in terms of required magnetic field modulation strengths and frequencies. A normalized mean squared error of below 10% can be achieved for acceleration factors of up to 8 using modulation field strengths comparable to the readout gradient strength at modulation frequencies in the range of 5 to 20 kHz. CONCLUSION: Spread-spectrum MRI represents a new approach to accelerate image acquisition, and it can be independently combined with traditional parallel imaging techniques based on local receive coil sensitivities.

Modeling confounding by half-sibling regression.

We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as "half-sibling regression," is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application.

Shifts of Gamma Phase across Primary Visual Cortical Sites Reflect Dynamic Stimulus-Modulated Information Transfer.

Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50-80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections.

Identification of causal relations in neuroimaging data with latent confounders: An instrumental variable approach.

We consider the task of inferring causal relations in brain imaging data with latent confounders. Using a priori knowledge that randomized experimental conditions cannot be effects of brain activity, we derive statistical conditions that are sufficient for establishing a causal relation between two neural processes, even in the presence of latent confounders. We provide an algorithm to test these conditions on empirical data, and illustrate its performance on simulated as well as on experimentally recorded EEG data.

Causal interpretation rules for encoding and decoding models in neuroimaging.

Causal terminology is often introduced in the interpretation of encoding and decoding models trained on neuroimaging data. In this article, we investigate which causal statements are warranted and which ones are not supported by empirical evidence. We argue that the distinction between encoding and decoding models is not sufficient for this purpose: relevant features in encoding and decoding models carry a different meaning in stimulus- and in response-based experimental paradigms.We show that only encoding models in the stimulus-based setting support unambiguous causal interpretations. By combining encoding and decoding models trained on the same data, however, we obtain insights into causal relations beyond those that are implied by each individual model type. We illustrate the empirical relevance of our theoretical findings on EEG data recorded during a visuo-motor learning task.

Blind multirigid retrospective motion correction of MR images.

PURPOSE: Physiological nonrigid motion is inevitable when imaging, e.g., abdominal viscera, and can lead to serious deterioration of the image quality. Prospective techniques for motion correction can handle only special types of nonrigid motion, as they only allow global correction. Retrospective methods developed so far need guidance from navigator sequences or external sensors. We propose a fully retrospective nonrigid motion correction scheme that only needs raw data as an input. METHODS: Our method is based on a forward model that describes the effects of nonrigid motion by partitioning the image into patches with locally rigid motion. Using this forward model, we construct an objective function that we can optimize with respect to both unknown motion parameters per patch and the underlying sharp image. RESULTS: We evaluate our method on both synthetic and real data in 2D and 3D. In vivo data was acquired using standard imaging sequences. The correction algorithm significantly improves the image quality. Our compute unified device architecture (CUDA)-enabled graphic processing unit implementation ensures feasible computation times. CONCLUSION: The presented technique is the first computationally feasible retrospective method that uses the raw data of standard imaging sequences, and allows to correct for nonrigid motion without guidance from external motion sensors.

Causal discovery via reproducing kernel Hilbert space embeddings.

Causal discovery via the asymmetry between the cause and the effect has proved to be a promising way to infer the causal direction from observations. The basic idea is to assume that the mechanism generating the cause distribution p(x) and that generating the conditional distribution p(y|x) correspond to two independent natural processes and thus p(x) and p(y|x) fulfill some sort of independence condition. However, in many situations, the independence condition does not hold for the anticausal direction; if we consider p(x, y) as generated via p(y)p(x|y), then there are usually some contrived mutual adjustments between p(y) and p(x|y). This kind of asymmetry can be exploited to identify the causal direction. Based on this postulate, in this letter, we define an uncorrelatedness criterion between p(x) and p(y|x) and, based on this uncorrelatedness, show asymmetry between the cause and the effect in terms that a certain complexity metric on p(x) and p(y|x) is less than the complexity metric on p(y) and p(x|y). We propose a Hilbert space embedding-based method EMD (an abbreviation for EMbeDding) to calculate the complexity metric and show that this method preserves the relative magnitude of the complexity metric. Based on the complexity metric, we propose an efficient kernel-based algorithm for causal discovery. The contribution of this letter is threefold. It allows a general transformation from the cause to the effect involving the noise effect and is applicable to both one-dimensional and high-dimensional data. Furthermore it can be used to infer the causal ordering for multiple variables. Extensive experiments on simulated and real-world data are conducted to show the effectiveness of the proposed method.

Learning strategies in table tennis using inverse reinforcement learning.

Learning a complex task such as table tennis is a challenging problem for both robots and humans. Even after acquiring the necessary motor skills, a strategy is needed to choose where and how to return the ball to the opponent's court in order to win the game. The data-driven identification of basic strategies in interactive tasks, such as table tennis, is a largely unexplored problem. In this paper, we suggest a computational model for representing and inferring strategies, based on a Markov decision problem, where the reward function models the goal of the task as well as the strategic information. We show how this reward function can be discovered from demonstrations of table tennis matches using model-free inverse reinforcement learning. The resulting framework allows to identify basic elements on which the selection of striking movements is based. We tested our approach on data collected from players with different playing styles and under different playing conditions. The estimated reward function was able to capture expert-specific strategic information that sufficed to distinguish the expert among players with different skill levels as well as different playing styles.

Predicting motor learning performance from Electroencephalographic data.

BACKGROUND: Research on the neurophysiological correlates of visuomotor integration and learning (VMIL) has largely focused on identifying learning-induced activity changes in cortical areas during motor execution. While such studies have generated valuable insights into the neural basis of VMIL, little is known about the processes that represent the current state of VMIL independently of motor execution. Here, we present empirical evidence that a subject's performance in a 3D reaching task can be predicted on a trial-to-trial basis from pre-trial electroencephalographic (EEG) data. This evidence provides novel insights into the brain states that support successful VMIL. METHODS: Six healthy subjects, attached to a seven degrees-of-freedom (DoF) robot with their right arm, practiced 3D reaching movements in a virtual space, while an EEG recorded their brain's electromagnetic field. A random forest ensemble classifier was used to predict the next trial's performance, as measured by the time needed to reach the goal, from pre-trial data using a leave-one-subject-out cross-validation procedure. RESULTS: The learned models successfully generalized to novel subjects. An analysis of the brain regions, on which the models based their predictions, revealed areas matching prevalent motor learning models. In these brain areas, the α/µ frequency band (8-14 Hz) was found to be most relevant for performance prediction. CONCLUSIONS: VMIL induces changes in cortical processes that extend beyond motor execution, indicating a more complex role of these processes than previously assumed. Our results further suggest that the capability of subjects to modulate their α/µ bandpower in brain regions associated with motor learning may be related to performance in VMIL. Accordingly, training subjects in α/µ-modulation, e.g., by means of a brain-computer interface (BCI), may have a beneficial impact on VMIL.

A gene expression map of Arabidopsis thaliana development.

Regulatory regions of plant genes tend to be more compact than those of animal genes, but the complement of transcription factors encoded in plant genomes is as large or larger than that found in those of animals. Plants therefore provide an opportunity to study how transcriptional programs control multicellular development. We analyzed global gene expression during development of the reference plant Arabidopsis thaliana in samples covering many stages, from embryogenesis to senescence, and diverse organs. Here, we provide a first analysis of this data set, which is part of the AtGenExpress expression atlas. We observed that the expression levels of transcription factor genes and signal transduction components are similar to those of metabolic genes. Examining the expression patterns of large gene families, we found that they are often more similar than would be expected by chance, indicating that many gene families have been co-opted for specific developmental processes.