Surfing the OCEAN: The machine learning psycholexical approach 2.0 to detect personality traits in texts.

OBJECTIVE: We aimed to develop a machine learning model to infer OCEAN traits from text. BACKGROUND: The psycholexical approach allows retrieving information about personality traits from human language. However, it has rarely been applied because of methodological and practical issues that current computational advancements could overcome. METHOD: Classical taxonomies and a large Yelp corpus were leveraged to learn an embedding for each personality trait. These embeddings were used to train a feedforward neural network for predicting trait values. Their generalization performances have been evaluated through two external validation studies involving experts (N = 11) and laypeople (N = 100) in a discrimination task about the best markers of each trait and polarity. RESULTS: Intrinsic validation of the model yielded excellent results, with R2 values greater than 0.78. The validation studies showed a high proportion of matches between participants' choices and model predictions, confirming its efficacy in identifying new terms related to the OCEAN traits. The best performance was observed for agreeableness and extraversion, especially for their positive polarities. The model was less efficient in identifying the negative polarity of openness and conscientiousness. CONCLUSIONS: This innovative methodology can be considered a "psycholexical approach 2.0," contributing to research in personality and its practical applications in many fields.

Non Stationary Multi-Armed Bandit: Empirical Evaluation of a New Concept Drift-Aware Algorithm.

The Multi-Armed Bandit (MAB) problem has been extensively studied in order to address real-world challenges related to sequential decision making. In this setting, an agent selects the best action to be performed at time-step t, based on the past rewards received by the environment. This formulation implicitly assumes that the expected payoff for each action is kept stationary by the environment through time. Nevertheless, in many real-world applications this assumption does not hold and the agent has to face a non-stationary environment, that is, with a changing reward distribution. Thus, we present a new MAB algorithm, named f-Discounted-Sliding-Window Thompson Sampling (f-dsw TS), for non-stationary environments, that is, when the data streaming is affected by concept drift. The f-dsw TS algorithm is based on Thompson Sampling (TS) and exploits a discount factor on the reward history and an arm-related sliding window to contrast concept drift in non-stationary environments. We investigate how to combine these two sources of information, namely the discount factor and the sliding window, by means of an aggregation function f(.). In particular, we proposed a pessimistic (f=min), an optimistic (f=max), as well as an averaged (f=mean) version of the f-dsw TS algorithm. A rich set of numerical experiments is performed to evaluate the f-dsw TS algorithm compared to both stationary and non-stationary state-of-the-art TS baselines. We exploited synthetic environments (both randomly-generated and controlled) to test the MAB algorithms under different types of drift, that is, sudden/abrupt, incremental, gradual and increasing/decreasing drift. Furthermore, we adapt four real-world active learning tasks to our framework-a prediction task on crimes in the city of Baltimore, a classification task on insects species, a recommendation task on local web-news, and a time-series analysis on microbial organisms in the tropical air ecosystem. The f-dsw TS approach emerges as the best performing MAB algorithm. At least one of the versions of f-dsw TS performs better than the baselines in synthetic environments, proving the robustness of f-dsw TS under different concept drift types. Moreover, the pessimistic version (f=min) results as the most effective in all real-world tasks.

Gene network inference using continuous time Bayesian networks: a comparative study and application to Th17 cell differentiation.

BACKGROUND: Dynamic aspects of gene regulatory networks are typically investigated by measuring system variables at multiple time points. Current state-of-the-art computational approaches for reconstructing gene networks directly build on such data, making a strong assumption that the system evolves in a synchronous fashion at fixed points in time. However, nowadays omics data are being generated with increasing time course granularity. Thus, modellers now have the possibility to represent the system as evolving in continuous time and to improve the models' expressiveness. RESULTS: Continuous time Bayesian networks are proposed as a new approach for gene network reconstruction from time course expression data. Their performance was compared to two state-of-the-art methods: dynamic Bayesian networks and Granger causality analysis. On simulated data, the methods comparison was carried out for networks of increasing size, for measurements taken at different time granularity densities and for measurements unevenly spaced over time. Continuous time Bayesian networks outperformed the other methods in terms of the accuracy of regulatory interactions learnt from data for all network sizes. Furthermore, their performance degraded smoothly as the size of the network increased. Continuous time Bayesian networks were significantly better than dynamic Bayesian networks for all time granularities tested and better than Granger causality for dense time series. Both continuous time Bayesian networks and Granger causality performed robustly for unevenly spaced time series, with no significant loss of performance compared to the evenly spaced case, while the same did not hold true for dynamic Bayesian networks. The comparison included the IRMA experimental datasets which confirmed the effectiveness of the proposed method. Continuous time Bayesian networks were then applied to elucidate the regulatory mechanisms controlling murine T helper 17 (Th17) cell differentiation and were found to be effective in discovering well-known regulatory mechanisms, as well as new plausible biological insights. CONCLUSIONS: Continuous time Bayesian networks were effective on networks of both small and large size and were particularly feasible when the measurements were not evenly distributed over time. Reconstruction of the murine Th17 cell differentiation network using continuous time Bayesian networks revealed several autocrine loops, suggesting that Th17 cells may be auto regulating their own differentiation process.

Edge and modular significance assessment in individual-specific networks.

Individual-specific networks, defined as networks of nodes and connecting edges that are specific to an individual, are promising tools for precision medicine. When such networks are biological, interpretation of functional modules at an individual level becomes possible. An under-investigated problem is relevance or "significance" assessment of each individual-specific network. This paper proposes novel edge and module significance assessment procedures for weighted and unweighted individual-specific networks. Specifically, we propose a modular Cook's distance using a method that involves iterative modeling of one edge versus all the others within a module. Two procedures assessing changes between using all individuals and using all individuals but leaving one individual out (LOO) are proposed as well (LOO-ISN, MultiLOO-ISN), relying on empirically derived edges. We compare our proposals to competitors, including adaptions of OPTICS, kNN, and Spoutlier methods, by an extensive simulation study, templated on real-life scenarios for gene co-expression and microbial interaction networks. Results show the advantages of performing modular versus edge-wise significance assessments for individual-specific networks. Furthermore, modular Cook's distance is among the top performers across all considered simulation settings. Finally, the identification of outlying individuals regarding their individual-specific networks, is meaningful for precision medicine purposes, as confirmed by network analysis of microbiome abundance profiles.

Conformational and functional analysis of molecular dynamics trajectories by self-organising maps.

BACKGROUND: Molecular dynamics (MD) simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs) were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering. RESULTS: The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions. CONCLUSIONS: The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to conformational ensembles from other sources.

Classification of dendritic cell phenotypes from gene expression data.

BACKGROUND: The selection of relevant genes for sample classification is a common task in many gene expression studies. Although a number of tools have been developed to identify optimal gene expression signatures, they often generate gene lists that are too long to be exploited clinically. Consequently, researchers in the field try to identify the smallest set of genes that provide good sample classification. We investigated the genome-wide expression of the inflammatory phenotype in dendritic cells. Dendritic cells are a complex group of cells that play a critical role in vertebrate immunity. Therefore, the prediction of the inflammatory phenotype in these cells may help with the selection of immune-modulating compounds. RESULTS: A data mining protocol was applied to microarray data for murine cell lines treated with various inflammatory stimuli. The learning and validation data sets consisted of 155 and 49 samples, respectively. The data mining protocol reduced the number of probe sets from 5,802 to 10, then from 10 to 6 and finally from 6 to 3. The performances of a set of supervised classification models were compared. The best accuracy, when using the six following genes --Il12b, Cd40, Socs3, Irgm1, Plin2 and Lgals3bp-- was obtained by Tree Augmented Naïve Bayes and Nearest Neighbour (91.8%). Using the smallest set of three genes --Il12b, Cd40 and Socs3-- the performance remained satisfactory and the best accuracy was with Support Vector Machine (95.9%). These data mining models, using data for the genes Il12b, Cd40 and Socs3, were validated with a human data set consisting of 27 samples. Support Vector Machines (71.4%) and Nearest Neighbour (92.6%) gave the worst performances, but the remaining models correctly classified all the 27 samples. CONCLUSIONS: The genes selected by the data mining protocol proposed were shown to be informative for discriminating between inflammatory and steady-state phenotypes in dendritic cells. The robustness of the data mining protocol was confirmed by the accuracy for a human data set, when using only the following three genes: Il12b, Cd40 and Socs3. In summary, we analysed the longitudinal pattern of expression in dendritic cells stimulated with activating agents with the aim of identifying signatures that would predict or explain the dentritic cell response to an inflammatory agent.

[Does free assumption of water from one hour after extubation reduce thirst without increasing complications in heart surgery patients?]. / L'assunzione libera di acqua, nei pazienti cardiochirurgici, a partire da un'ora dall'estubazione, può ridurre la sensazione di sete senza aumentare le complicanze?

OBJECT: The aim of this study was to assess whether free assumption of water in heart surgery patients, as early as one hour after extubation, produces measurable differences in thirst, nausea and vomiting. METHODS: Randomized controlled trial (pilot phase), by sex and age. Eventual cases of dysphagia are identified by both a functional examination and a water test. The sense of thirst and sickness are registered 1 hour post-extubation and subsequently at the 3rd, 6th and 12th hour using an NRS-scale 0-10. Data analysis was performed using a logistic regression model. RESULTS: 54 patients have been enrolled in the study. The sense of thirst is diminished in 17.39% of female, in 24.29% of male, leading to a total reduction in 22.58% of patients. The sense of sickness is arisen in 13.04% of female, in 2.86% of male, leading to a total rise of 5.38% of patients. Moreover, the sensation of thirst is diminished in 33.33% of patients with free water intake (treatment group), but only in 16.07% of patients who cannot drink water (control group). Finally, as far as the sensation of sickness is concerned, our results show a rise of 11.11% in patients with free water intake, higher if compared to 1.79% of the control group, but smaller than the value indicated in the literature. DISCUSSION: The collected data showed that drinking water from one hour after extubation had a positive effect without a significant increase in the patient's perception of nausea.

Modeling Approaches Reveal New Regulatory Networks in Aspergillus fumigatus Metabolism.

Systems biology approaches are extensively used to model and reverse-engineer gene regulatory networks from experimental data. Indoleamine 2,3-dioxygenases (IDOs)-belonging in the heme dioxygenase family-degrade l-tryptophan to kynurenines. These enzymes are also responsible for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). As such, they are expressed by a variety of species, including fungi. Interestingly, Aspergillus may degrade l-tryptophan not only via IDO but also via alternative pathways. Deciphering the molecular interactions regulating tryptophan metabolism is particularly critical for novel drug target discovery designed to control pathogen determinants in invasive infections. Using continuous time Bayesian networks over a time-course gene expression dataset, we inferred the global regulatory network controlling l-tryptophan metabolism. The method unravels a possible novel approach to target fungal virulence factors during infection. Furthermore, this study represents the first application of continuous-time Bayesian networks as a gene network reconstruction method in Aspergillus metabolism. The experiment showed that the applied computational approach may improve the understanding of metabolic networks over traditional pathways.

A comparison between discrete and continuous time Bayesian networks in learning from clinical time series data with irregularity.

BACKGROUND: Recently, mobile devices, such as smartphones, have been introduced into healthcare research to substitute paper diaries as data-collection tools in the home environment. Such devices support collecting patient data at different time points over a long period, resulting in clinical time-series data with high temporal complexity, such as time irregularities. Analysis of such time series poses new challenges for machine-learning techniques. The clinical context for the research discussed in this paper is home monitoring in chronic obstructive pulmonary disease (COPD). OBJECTIVE: The goal of the present research is to find out which properties of temporal Bayesian network models allow to cope best with irregularly spaced multivariate clinical time-series data. METHODS: Two mainstream temporal Bayesian network models of multivariate clinical time series are studied: dynamic Bayesian networks, where the system is described as a snapshot at discrete time points, and continuous time Bayesian networks, where transitions between states are modeled in continuous time. Their capability of learning from clinical time series that vary in nature are extensively studied. In order to compare the two temporal Bayesian network types for regularly and irregularly spaced time-series data, three typical ways of observing time-series data were investigated: (1) regularly spaced in time with a fixed rate; (2) irregularly spaced and missing completely at random at discrete time points; (3) irregularly spaced and missing at random at discrete time points. In addition, similar experiments were carried out using real-world COPD patient data where observations are unevenly spaced. RESULTS: For regularly spaced time series, the dynamic Bayesian network models outperform the continuous time Bayesian networks. Similarly, if the data is missing completely at random, discrete-time models outperform continuous time models in most situations. For more realistic settings where data is not missing completely at random, the situation is more complicated. In simulation experiments, both models perform similarly if there is strong prior knowledge available about the missing data distribution. Otherwise, continuous time Bayesian networks perform better. In experiments with unevenly spaced real-world data, we surprisingly found that a dynamic Bayesian network where time is ignored performs similar to a continuous time Bayesian network. CONCLUSION: The results confirm conventional wisdom that discrete-time Bayesian networks are appropriate when learning from regularly spaced clinical time series. Similarly, we found that time series where the missingness occurs completely at random, dynamic Bayesian networks are an appropriate choice. However, for complex clinical time-series data that motivated this research, the continuous-time models are at least competitive and sometimes better than their discrete-time counterparts. Furthermore, continuous-time models provide additional benefits of being able to provide more fine-grained predictions than discrete-time models, which will be of practical relevance in clinical applications.

Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans.

T helper 17 (TH17) cells represent a pivotal adaptive cell subset involved in multiple immune disorders in mammalian species. Deciphering the molecular interactions regulating TH17 cell differentiation is particularly critical for novel drug target discovery designed to control maladaptive inflammatory conditions. Using continuous time Bayesian networks over a time-course gene expression dataset, we inferred the global regulatory network controlling TH17 differentiation. From the network, we identified the Prdm1 gene encoding the B lymphocyte-induced maturation protein 1 as a crucial negative regulator of human TH17 cell differentiation. The results have been validated by perturbing Prdm1 expression on freshly isolated CD4(+) naïve T cells: reduction of Prdm1 expression leads to augmentation of IL-17 release. These data unravel a possible novel target to control TH17 polarization in inflammatory disorders. Furthermore, this study represents the first in vitro validation of continuous time Bayesian networks as gene network reconstruction method and as hypothesis generation tool for wet-lab biological experiments.

Some numerical aspects of the training problem for feed-forward neural nets.

This paper considers the feed-forward training problem from the numerical point of view, in particular the conditioning of the problem. It is well known that the feed-forward training problem is often ill-conditioned; this affects the behaviour of training algorithms, the choice of such algorithms and the quality of the solutions achieved. A geometric interpretation of ill-conditioning is explored and an example of function approximation is analysed in detail.