q-Diffusion leverages the full dimensionality of gene coexpression in single-cell transcriptomics.

Unlocking the full dimensionality of single-cell RNA sequencing data (scRNAseq) is the next frontier to a richer, fuller understanding of cell biology. We introduce q-diffusion, a framework for capturing the coexpression structure of an entire library of genes, improving on state-of-the-art analysis tools. The method is demonstrated via three case studies. In the first, q-diffusion helps gain statistical significance for differential effects on patient outcomes when analyzing the CALGB/SWOG 80405 randomized phase III clinical trial, suggesting precision guidance for the treatment of metastatic colorectal cancer. Secondly, q-diffusion is benchmarked against existing scRNAseq classification methods using an in vitro PBMC dataset, in which the proposed method discriminates IFN-γ stimulation more accurately. The same case study demonstrates improvements in unsupervised cell clustering with the recent Tabula Sapiens human atlas. Finally, a local distributional segmentation approach for spatial scRNAseq, driven by q-diffusion, yields interpretable structures of human cortical tissue.

Effect of CSN3 Gene Polymorphism on the Formation of Milk Gels Induced by Physical, Chemical, and Biotechnological Factors.

During the last decade, research into genetic markers in the casein gene cluster has been actively introduced in cattle breeding programs. A special interest has been paid to the polymorphism of the CSN3 gene, responsible for the expression of the k-casein, playing a key role in protein coagulation, interaction with whey proteins, stabilization, and aggregation of casein micelles. This paper aimed to determine the effect of CSN3 genetic polymorphism on acid; rennet; acid-rennet; heat- and acid-induced as well as heat- and calcium-induced coagulation in skimmed milk; and protein-standardized milk systems (UF, NF, RO, VE). The influence of polymorphic variants of the CSN3 gene on the coagulation ability of milk proteins was assessed by the particle size of casein micelles, protein retention factor in the clot, and coagulation ability (duration of induction period, mass coagulation period, dynamic viscosity in gel point). The correlation between CSN3 gene polymorphism and protein coagulation was revealed. Milk systems obtained from CSN3 BB milk were found to have the shortest duration of coagulation, formation of better gel strength values, and increased yield compared to CSN3 AA. This study will improve the efficiency of milk processing and optimize the technology of dairy product production.

Identifying geopolitical event precursors using attention-based LSTMs.

Forecasting societal events such as civil unrest, mass protests, and violent conflicts is a challenging problem with several important real-world applications in planning and policy making. While traditional forecasting approaches have typically relied on historical time series for generating such forecasts, recent research has focused on using open source surrogate data for more accurate and timely forecasts. Furthermore, leveraging such data can also help to identify precursors of those events that can be used to gain insights into the generated forecasts. The key challenge is to develop a unified framework for forecasting and precursor identification that can deal with missing historical data. Other challenges include sufficient flexibility in handling different types of events and providing interpretable representations of identified precursors. Although existing methods exhibit promising performance for predictive modeling in event detection, these models do not adequately address the above challenges. Here, we propose a unified framework based on an attention-based long short-term memory (LSTM) model to simultaneously forecast events with sequential text datasets as well as identify precursors at different granularity such as documents and document excerpts. The key idea is to leverage word context in sequential and time-stamped documents such as news articles and blogs for learning a rich set of precursors. We validate the proposed framework by conducting extensive experiments with two real-world datasets-military action and violent conflicts in the Middle East and mass protests in Latin America. Our results show that overall, the proposed approach generates more accurate forecasts compared to the existing state-of-the-art methods, while at the same time producing a rich set of precursors for the forecasted events.

NERO: a biomedical named-entity (recognition) ontology with a large, annotated corpus reveals meaningful associations through text embedding.

Machine reading (MR) is essential for unlocking valuable knowledge contained in millions of existing biomedical documents. Over the last two decades1,2, the most dramatic advances in MR have followed in the wake of critical corpus development3. Large, well-annotated corpora have been associated with punctuated advances in MR methodology and automated knowledge extraction systems in the same way that ImageNet4 was fundamental for developing machine vision techniques. This study contributes six components to an advanced, named entity analysis tool for biomedicine: (a) a new, Named Entity Recognition Ontology (NERO) developed specifically for describing textual entities in biomedical texts, which accounts for diverse levels of ambiguity, bridging the scientific sublanguages of molecular biology, genetics, biochemistry, and medicine; (b) detailed guidelines for human experts annotating hundreds of named entity classes; (c) pictographs for all named entities, to simplify the burden of annotation for curators; (d) an original, annotated corpus comprising 35,865 sentences, which encapsulate 190,679 named entities and 43,438 events connecting two or more entities; (e) validated, off-the-shelf, named entity recognition (NER) automated extraction, and; (f) embedding models that demonstrate the promise of biomedical associations embedded within this corpus.

A survey of human judgement and quantitative forecasting methods.

This paper's top-level goal is to provide an overview of research conducted in the many academic domains concerned with forecasting. By providing a summary encompassing these domains, this survey connects them, establishing a common ground for future discussions. To this end, we survey literature on human judgement and quantitative forecasting as well as hybrid methods that involve both humans and algorithmic approaches. The survey starts with key search terms that identified more than 280 publications in the fields of computer science, operations research, risk analysis, decision science, psychology and forecasting. Results show an almost 10-fold increase in the application-focused forecasting literature between the 1990s and the current decade, with a clear rise of quantitative, data-driven forecasting models. Comparative studies of quantitative methods and human judgement show that (1) neither method is universally superior, and (2) the better method varies as a function of factors such as availability, quality, extent and format of data, suggesting that (3) the two approaches can complement each other to yield more accurate and resilient models. We also identify four research thrusts in the human/machine-forecasting literature: (i) the choice of the appropriate quantitative model, (ii) the nature of the interaction between quantitative models and human judgement, (iii) the training and incentivization of human forecasters, and (iv) the combination of multiple forecasts (both algorithmic and human) into one. This review surveys current research in all four areas and argues that future research in the field of human/machine forecasting needs to consider all of them when investigating predictive performance. We also address some of the ethical dilemmas that might arise due to the combination of quantitative models with human judgement.

Methodological Approaches to DNA Authentication of Foods, Wines and Raw Materials for Their Production.

DNA authentication of wines is a process of verifying their authenticity by genetic identification of the main plant component. The sample preparation of experimental and commercial wines was carried out by precipitation of wine debris by centrifugation with preliminary exposure with precipitators and co-precipitators, including developed macro- and micro-volume methods applicable to white or red wines, using polyvinylpyrrolidone as a co-precipitator. Addition of 2-mercaptoethanol and proteinase K to the lysing solution made it possible to adapt the technology for DNA extraction from the precipitated wine debris. The additionally tested technique of DNA extraction from wine debris by dimethyl sulfoxide (DMSO) lysis had fewer stages and, consequently, a lower risk of contamination. The results of further testing of one of the designed primer pairs (UFGT-F1 and UFGT-R1) in conjunction with the tested methods of wine material sample preparation and nucleic acid extraction, showed the advantage in the given set of oligonucleotides over previously used ones in terms of sensitivity, specificity and reproducibility. The developing strategy for genetic identification of grape varieties and DNA authentication of wines produced from them based on direct sequencing of polymerase chain reaction (PCR) products is implemented by interpreting the detected polymorphic positions of variable Vitis vinifera L. UFGT gene locus with distribution and split into 13 UFGT gene-associated groups.

Discovering Higher-Order Interactions Through Neural Information Decomposition.

If regularity in data takes the form of higher-order functions among groups of variables, models which are biased towards lower-order functions may easily mistake the data for noise. To distinguish whether this is the case, one must be able to quantify the contribution of different orders of dependence to the total information. Recent work in information theory attempts to do this through measures of multivariate mutual information (MMI) and information decomposition (ID). Despite substantial theoretical progress, practical issues related to tractability and learnability of higher-order functions are still largely unaddressed. In this work, we introduce a new approach to information decomposition-termed Neural Information Decomposition (NID)-which is both theoretically grounded, and can be efficiently estimated in practice using neural networks. We show on synthetic data that NID can learn to distinguish higher-order functions from noise, while many unsupervised probability models cannot. Additionally, we demonstrate the usefulness of this framework as a tool for exploring biological and artificial neural networks.

Quantifying machine influence over human forecasters.

Crowdsourcing human forecasts and machine learning models each show promise in predicting future geopolitical outcomes. Crowdsourcing increases accuracy by pooling knowledge, which mitigates individual errors. On the other hand, advances in machine learning have led to machine models that increase accuracy due to their ability to parameterize and adapt to changing environments. To capitalize on the unique advantages of each method, recent efforts have shown improvements by "hybridizing" forecasts-pairing human forecasters with machine models. This study analyzes the effectiveness of such a hybrid system. In a perfect world, independent reasoning by the forecasters combined with the analytic capabilities of the machine models should complement each other to arrive at an ultimately more accurate forecast. However, well-documented biases describe how humans often mistrust and under-utilize such models in their forecasts. In this work, we present a model that can be used to estimate the trust that humans assign to a machine. We use forecasts made in the absence of machine models as prior beliefs to quantify the weights placed on the models. Our model can be used to uncover other aspects of forecasters' decision-making processes. We find that forecasters trust the model rarely, in a pattern that suggests they treat machine models similarly to expert advisors, but only the best forecasters trust the models when they can be expected to perform well. We also find that forecasters tend to choose models that conform to their prior beliefs as opposed to anchoring on the model forecast. Our results suggest machine models can improve the judgment of a human pool but highlight the importance of accounting for trust and cognitive biases involved in the human judgment process.

Stacking models for nearly optimal link prediction in complex networks.

Most real-world networks are incompletely observed. Algorithms that can accurately predict which links are missing can dramatically speed up network data collection and improve network model validation. Many algorithms now exist for predicting missing links, given a partially observed network, but it has remained unknown whether a single best predictor exists, how link predictability varies across methods and networks from different domains, and how close to optimality current methods are. We answer these questions by systematically evaluating 203 individual link predictor algorithms, representing three popular families of methods, applied to a large corpus of 550 structurally diverse networks from six scientific domains. We first show that individual algorithms exhibit a broad diversity of prediction errors, such that no one predictor or family is best, or worst, across all realistic inputs. We then exploit this diversity using network-based metalearning to construct a series of "stacked" models that combine predictors into a single algorithm. Applied to a broad range of synthetic networks, for which we may analytically calculate optimal performance, these stacked models achieve optimal or nearly optimal levels of accuracy. Applied to real-world networks, stacked models are superior, but their accuracy varies strongly by domain, suggesting that link prediction may be fundamentally easier in social networks than in biological or technological networks. These results indicate that the state of the art for link prediction comes from combining individual algorithms, which can achieve nearly optimal predictions. We close with a brief discussion of limitations and opportunities for further improvements.

Multitask learning and benchmarking with clinical time series data.

Health care is one of the most exciting frontiers in data mining and machine learning. Successful adoption of electronic health records (EHRs) created an explosion in digital clinical data available for analysis, but progress in machine learning for healthcare research has been difficult to measure because of the absence of publicly available benchmark data sets. To address this problem, we propose four clinical prediction benchmarks using data derived from the publicly available Medical Information Mart for Intensive Care (MIMIC-III) database. These tasks cover a range of clinical problems including modeling risk of mortality, forecasting length of stay, detecting physiologic decline, and phenotype classification. We propose strong linear and neural baselines for all four tasks and evaluate the effect of deep supervision, multitask training and data-specific architectural modifications on the performance of neural models.

Uncovering Biologically Coherent Peripheral Signatures of Health and Risk for Alzheimer's Disease in the Aging Brain.

Brain aging is a multifaceted process that remains poorly understood. Despite significant advances in technology, progress toward identifying reliable risk factors for suboptimal brain health requires realistically complex analytic methods to explain relationships between genetics, biology, and environment. Here we show the utility of a novel unsupervised machine learning technique - Correlation Explanation (CorEx) - to discover how individual measures from structural brain imaging, genetics, plasma, and CSF markers can jointly provide information on risk for Alzheimer's disease (AD). We examined 829 participants (M age: 75.3 ± 6.9 years; 350 women and 479 men) from the Alzheimer's Disease Neuroimaging Initiative database to identify multivariate predictors of cognitive decline and brain atrophy over a 1-year period. Our sample included 231 cognitively normal individuals, 397 with mild cognitive impairment (MCI), and 201 with AD as their baseline diagnosis. Analyses revealed latent factors based on data-driven combinations of plasma markers and brain metrics, that were aligned with established biological pathways in AD. These factors were able to improve disease prediction along the trajectory from normal cognition and MCI to AD, with an area under the receiver operating curve of up to 99%, and prediction accuracy of up to 89.9% on independent "held out" testing data. Further, the most important latent factors that predicted AD consisted of a novel set of variables that are essential for cardiovascular, immune, and bioenergetic functions. Collectively, these results demonstrate the strength of unsupervised network measures in the detection and prediction of AD.

Emergence of Leadership in Communication.

We study a neuro-inspired model that mimics a discussion (or information dissemination) process in a network of agents. During their interaction, agents redistribute activity and network weights, resulting in emergence of leader(s). The model is able to reproduce the basic scenarios of leadership known in nature and society: laissez-faire (irregular activity, weak leadership, sizable inter-follower interaction, autonomous sub-leaders); participative or democratic (strong leadership, but with feedback from followers); and autocratic (no feedback, one-way influence). Several pertinent aspects of these scenarios are found as well-e.g., hidden leadership (a hidden clique of agents driving the official autocratic leader), and successive leadership (two leaders influence followers by turns). We study how these scenarios emerge from inter-agent dynamics and how they depend on behavior rules of agents-in particular, on their inertia against state changes.

Using Social Media, Online Social Networks, and Internet Search as Platforms for Public Health Interventions: A Pilot Study.

OBJECTIVE: To pilot public health interventions at women potentially interested in maternity care via campaigns on social media (Twitter), social networks (Facebook), and online search engines (Google Search). DATA SOURCES/STUDY SETTING: Primary data from Twitter, Facebook, and Google Search on users of these platforms in Los Angeles between March and July 2014. STUDY DESIGN: Observational study measuring the responses of targeted users of Twitter, Facebook, and Google Search exposed to our sponsored messages soliciting them to start an engagement process by clicking through to a study website containing information on maternity care quality information for the Los Angeles market. PRINCIPAL FINDINGS: Campaigns reached a little more than 140,000 consumers each day across the three platforms, with a little more than 400 engagements each day. Facebook and Google search had broader reach, better engagement rates, and lower costs than Twitter. Costs to reach 1,000 targeted users were approximately in the same range as less well-targeted radio and TV advertisements, while initial engagements-a user clicking through an advertisement-cost less than $1 each. CONCLUSIONS: Our results suggest that commercially available online advertising platforms in wide use by other industries could play a role in targeted public health interventions.

Information-Theoretic Characterization of Blood Panel Predictors for Brain Atrophy and Cognitive Decline in the Elderly.

Cognitive decline in old age is tightly linked with brain atrophy, causing significant burden. It is critical to identify which biomarkers are most predictive of cognitive decline and brain atrophy in the elderly. In 566 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we used a novel unsupervised machine learning approach to evaluate an extensive list of more than 200 potential brain, blood and cerebrospinal fluid (CSF)-based predictors of cognitive decline. The method, called CorEx, discovers groups of variables with high multivariate mutual information and then constructs latent factors that explain these correlations. The approach produces a hierarchical structure and the predictive power of biological variables and latent factors are compared with regression. We found that a group of variables containing the well-known AD risk gene APOE and CSF tau and amyloid levels were highly correlated. This latent factor was the most predictive of cognitive decline and brain atrophy.

Understanding Confounding Effects in Linguistic Coordination: An Information-Theoretic Approach.

We suggest an information-theoretic approach for measuring stylistic coordination in dialogues. The proposed measure has a simple predictive interpretation and can account for various confounding factors through proper conditioning. We revisit some of the previous studies that reported strong signatures of stylistic accommodation, and find that a significant part of the observed coordination can be attributed to a simple confounding effect--length coordination. Specifically, longer utterances tend to be followed by longer responses, which gives rise to spurious correlations in the other stylistic features. We propose a test to distinguish correlations in length due to contextual factors (topic of conversation, user verbosity, etc.) and turn-by-turn coordination. We also suggest a test to identify whether stylistic coordination persists even after accounting for length coordination and contextual factors.

Opinion dynamics with confirmation bias.

BACKGROUND: Confirmation bias is the tendency to acquire or evaluate new information in a way that is consistent with one's preexisting beliefs. It is omnipresent in psychology, economics, and even scientific practices. Prior theoretical research of this phenomenon has mainly focused on its economic implications possibly missing its potential connections with broader notions of cognitive science. METHODOLOGY/PRINCIPAL FINDINGS: We formulate a (non-Bayesian) model for revising subjective probabilistic opinion of a confirmationally-biased agent in the light of a persuasive opinion. The revision rule ensures that the agent does not react to persuasion that is either far from his current opinion or coincides with it. We demonstrate that the model accounts for the basic phenomenology of the social judgment theory, and allows to study various phenomena such as cognitive dissonance and boomerang effect. The model also displays the order of presentation effect-when consecutively exposed to two opinions, the preference is given to the last opinion (recency) or the first opinion (primacy) -and relates recency to confirmation bias. Finally, we study the model in the case of repeated persuasion and analyze its convergence properties. CONCLUSIONS: The standard Bayesian approach to probabilistic opinion revision is inadequate for describing the observed phenomenology of persuasion process. The simple non-Bayesian model proposed here does agree with this phenomenology and is capable of reproducing a spectrum of effects observed in psychology: primacy-recency phenomenon, boomerang effect and cognitive dissonance. We point out several limitations of the model that should motivate its future development.

Coevolutionary networks of reinforcement-learning agents.

This paper presents a model of network formation in repeated games where the players adapt their strategies and network ties simultaneously using a simple reinforcement-learning scheme. It is demonstrated that the coevolutionary dynamics of such systems can be described via coupled replicator equations. We provide a comprehensive analysis for three-player two-action games, which is the minimum system size with nontrivial structural dynamics. In particular, we characterize the Nash equilibria (NE) in such games and examine the local stability of the rest points corresponding to those equilibria. We also study general n-player networks via both simulations and analytical methods and find that, in the absence of exploration, the stable equilibria consist of star motifs as the main building blocks of the network. Furthermore, in all stable equilibria the agents play pure strategies, even when the game allows mixed NE. Finally, we study the impact of exploration on learning outcomes and observe that there is a critical exploration rate above which the symmetric and uniformly connected network topology becomes stable.

Dynamics of Boltzmann Q learning in two-player two-action games.

We consider the dynamics of Q learning in two-player two-action games with a Boltzmann exploration mechanism. For any nonzero exploration rate the dynamics is dissipative, which guarantees that agent strategies converge to rest points that are generally different from the game's Nash equlibria (NEs). We provide a comprehensive characterization of the rest point structure for different games and examine the sensitivity of this structure with respect to the noise due to exploration. Our results indicate that for a class of games with multiple NEs the asymptotic behavior of learning dynamics can undergo drastic changes at critical exploration rates. Furthermore, we demonstrate that, for certain games with a single NE, it is possible to have additional rest points (not corresponding to any NE) that persist for a finite range of the exploration rates and disappear when the exploration rates of both players tend to zero.

Le Chatelier's principle in replicator dynamics.

The Le Chatelier principle states that physical equilibria are not only stable, but they also resist external perturbations via short-time negative-feedback mechanisms: a perturbation induces processes tending to diminish its results. The principle has deep roots, e.g., in thermodynamics it is closely related to the second law and the positivity of the entropy production. Here we study the applicability of the Le Chatelier principle to evolutionary game theory, i.e., to perturbations of a Nash equilibrium within the replicator dynamics. We show that the principle can be reformulated as a majorization relation. This defines a stability notion that generalizes the concept of evolutionary stability. We determine criteria for a Nash equilibrium to satisfy the Le Chatelier principle and relate them to mutualistic interactions (game-theoretical anticoordination) showing in which sense mutualistic replicators can be more stable than (say) competing ones. There are globally stable Nash equilibria, where the Le Chatelier principle is violated even locally: in contrast to the thermodynamic equilibrium a Nash equilibrium can amplify small perturbations, though both types of equilibria satisfy the detailed balance condition.

Maximizing influence propagation in networks with community structure.

We consider the algorithmic problem of selecting a set of target nodes that cause the biggest activation cascade in a network. In case when the activation process obeys the diminishing return property, a simple hill-climbing selection mechanism has been shown to achieve a provably good performance. Here we study models of influence propagation that exhibit critical behavior and where the property of diminishing returns does not hold. We demonstrate that in such systems the structural properties of networks can play a significant role. We focus on networks with two loosely coupled communities and show that the double-critical behavior of activation spreading in such systems has significant implications for the targeting strategies. In particular, we show that simple strategies that work well for homogenous networks can be overly suboptimal and suggest simple modification for improving the performance by taking into account the community structure.