Epigenetic modifications, particularly RNA methylation and histone alterations, play a crucial role in heredity, development, and disease. Among these, RNA 5-methylcytosine (m5C) is the most prevalent RNA modification in mammalian cells, essential for processes such as ribosome synthesis, translational fidelity, mRNA nuclear export, turnover, and translation. The increasing volume of nucleotide sequences has led to the development of machine learning-based predictors for m5C site prediction. However, these predictors often face challenges related to training data limitations and overfitting due to insufficient external validation. This study introduces m5C-Seq, an ensemble learning approach for RNA modification profiling, designed to address these issues. m5C-Seq employs a meta-classifier that integrates 15 probabilities generated from a novel, large dataset using systematic encoding methods to make final predictions. Demonstrating superior performance compared to existing predictors, m5C-Seq represents a significant advancement in accurate RNA modification profiling. The code and the newly established datasets are made available through GitHub at https://github.com/Z-Abbas/m5C-Seq.

Over recent decades, natural and artificial colloids, as well as nanoparticles, have been increasingly used in various applications. Consequently, with this rising consumption, surface and subsurface environments are more exposed to these particles. The presence of these particles and the colloid-facilitated transport of microorganisms, the interactions between dissolved contaminants and mobile colloids in porous media, and the fate and transport of colloids through groundwater-one of the primary sources of water supply for human societies-have attracted extensive research. This study investigates the performance of several image processing methods in the field of colloid detection, which is a prerequisite for the subsequent steps in porous media research. We employed four different categories of image processing approaches on microscopy images-segmentation-based methods, background-detection-based methods, filter-based methods, and morphology-based methods-to conduct the detection process of colloids. Eight methods were applied and subsequently analyzed in terms of their drawbacks and advantages to determine the best ones in this domain. Finally, we proposed an ensemble approach that leverages the strengths of the three best methods using a majority vote to detect colloids more accurately. In experiments, Precision, Recall, F-measure, and TCR criteria were considered as evaluation tools. Experimental results demonstrate the high accuracy of image processing methods in recognizing colloids. Among all these methods, morphology-based methods were the most successful, achieving the best detection performance and improving the limited distinguishing features of small colloids. Moreover, our ensemble approach, achieving perfect scores across all evaluation criteria, highlights its superiority compared with other detection methods.

Complex systems pose significant challenges to traditional scientific and statistical methods due to their inherent unpredictability and resistance to simplification. Accurately detecting complex behavior and the uncertainty which comes with it is therefore essential. Using the context of previous studies, we introduce a new information-theoretic measure, termed \"incoherence\". By using an adapted Jensen-Shannon Divergence across an ensemble of outcomes, we quantify the aleatoric uncertainty of the system. First we compared this measure to established statistical tests using both continuous and discrete data. Before demonstrating how incoherence can be applied to identify key characteristics of complex systems, including sensitivity to initial conditions, criticality, and response to perturbations.

BACKGROUND: Cancers are complex multi-genetic diseases that should be tackled in multi-target drug discovery scenarios. Computational methods are of great importance to accelerate the discovery of multi-target anticancer agents. Here, we employed a ligand-based approach by combining a perturbation-theory machine learning model derived from an ensemble of multilayer perceptron networks (PTML-EL-MLP) with the Fragment-Based Topological Design (FBTD) approach to rationally design and predict triple-target inhibitors against the cancerrelated proteins named Tropomyosin Receptor Kinase A (TRKA), poly[ADP-ribose] polymerase 1 (PARP-1), and Insulin-like Growth Factor 1 Receptor (IGF1R).
METHODS: We extracted the chemical and biological data from ChEMBL. We applied the Box- Jenkins approach to generate multi-label topological indices and subsequently created the PTML-EL-MLP model.
RESULTS: Our PTML-EL-MLP model exhibited an accuracy of around 80%. The application FBTD permitted the physicochemical and structural interpretation of the PTML-EL-MLP model, thus enabling a) the chemistry-driven analysis of different molecular fragments with a positive influence on the multi-target activity and b) the use of those favorable fragments as building blocks to virtually design four new drug-like molecules. The designed molecules were predicted as triple-target inhibitors against the aforementioned cancer-related proteins.
CONCLUSIONS: Our study envisages the capabilities of combining PTML modeling with FBTD for the generation of new chemical diversity for multi-target drug discovery in oncology research and beyond.

Postacute sequelae of COVID-19 (PASC), also known as long COVID, is a broad grouping of a range of long-term symptoms following acute COVID-19. These symptoms can occur across a range of biological systems, leading to challenges in determining risk factors for PASC and the causal etiology of this disorder. An understanding of characteristics that are predictive of future PASC is valuable, as this can inform the identification of high-risk individuals and future preventative efforts. However, current knowledge regarding PASC risk factors is limited.
Using a sample of 55,257 patients (at a ratio of 1 patient with PASC to 4 matched controls) from the National COVID Cohort Collaborative, as part of the National Institutes of Health Long COVID Computational Challenge, we sought to predict individual risk of PASC diagnosis from a curated set of clinically informed covariates. The National COVID Cohort Collaborative includes electronic health records for more than 22 million patients from 84 sites across the United States.
We predicted individual PASC status, given covariate information, using Super Learner (an ensemble machine learning algorithm also known as stacking) to learn the optimal combination of gradient boosting and random forest algorithms to maximize the area under the receiver operator curve. We evaluated variable importance (Shapley values) based on 3 levels: individual features, temporal windows, and clinical domains. We externally validated these findings using a holdout set of randomly selected study sites.
We were able to predict individual PASC diagnoses accurately (area under the curve 0.874). The individual features of the length of observation period, number of health care interactions during acute COVID-19, and viral lower respiratory infection were the most predictive of subsequent PASC diagnosis. Temporally, we found that baseline characteristics were the most predictive of future PASC diagnosis, compared with characteristics immediately before, during, or after acute COVID-19. We found that the clinical domains of health care use, demographics or anthropometry, and respiratory factors were the most predictive of PASC diagnosis.
The methods outlined here provide an open-source, applied example of using Super Learner to predict PASC status using electronic health record data, which can be replicated across a variety of settings. Across individual predictors and clinical domains, we consistently found that factors related to health care use were the strongest predictors of PASC diagnosis. This indicates that any observational studies using PASC diagnosis as a primary outcome must rigorously account for heterogeneous health care use. Our temporal findings support the hypothesis that clinicians may be able to accurately assess the risk of PASC in patients before acute COVID-19 diagnosis, which could improve early interventions and preventive care. Our findings also highlight the importance of respiratory characteristics in PASC risk assessment.
RR2-10.1101/2023.07.27.23293272.

Synaptic connectivity defines groups of neurons that engage in correlated activity during specific functional tasks. These co-active groups of neurons form ensembles, the operational units involved in, for example, sensory perception, motor coordination and memory (then called an engram). Traditionally, ensemble formation has been thought to occur via strengthening of synaptic connections via long-term potentiation (LTP) as a plasticity mechanism. This synaptic theory of memory arises from the learning rules formulated by Hebb and is consistent with many experimental observations. Here, we propose, as an alternative, that the intrinsic excitability of neurons and its plasticity constitute a second, non-synaptic mechanism that could be important for the initial formation of ensembles. Indeed, enhanced neural excitability is widely observed in multiple brain areas subsequent to behavioral learning. In cortical structures and the amygdala, excitability changes are often reported as transient, even though they can last tens of minutes to a few days. Perhaps it is for this reason that they have been traditionally considered as modulatory, merely supporting ensemble formation by facilitating LTP induction, without further involvement in memory function (memory allocation hypothesis). We here suggest-based on two lines of evidence-that beyond modulating LTP allocation, enhanced excitability plays a more fundamental role in learning. First, enhanced excitability constitutes a signature of active ensembles and, due to it, subthreshold synaptic connections become suprathreshold in the absence of synaptic plasticity (iceberg model). Second, enhanced excitability promotes the propagation of dendritic potentials toward the soma and allows for enhanced coupling of EPSP amplitude (LTP) to the spike output (and thus ensemble participation). This permissive gate model describes a need for permanently increased excitability, which seems at odds with its traditional consideration as a short-lived mechanism. We propose that longer modifications in excitability are made possible by a low threshold for intrinsic plasticity induction, suggesting that excitability might be on/off-modulated at short intervals. Consistent with this, in cerebellar Purkinje cells, excitability lasts days to weeks, which shows that in some circuits the duration of the phenomenon is not a limiting factor in the first place. In our model, synaptic plasticity defines the information content received by neurons through the connectivity network that they are embedded in. However, the plasticity of cell-autonomous excitability could dynamically regulate the ensemble participation of individual neurons as well as the overall activity state of an ensemble.

Extreme weather events, such as those associated with winds and precipitation, result in billions of euros in damages annually. While changes in extreme precipitation due to global warming have already been detected at sub-continental scales, their complex characteristics make them a challenges to asses at more regional scales. Extreme winds present an even greater challenge as the varying dynamical response to global warming exhibits high levels of uncertainty. This situation is complicated by local scale interactions with orography, cities, land-sea contrasts, etc. The dataset presented here attempts to address these challenges and provide information that will allow robust assessment of extreme winds and precipitation (maximum five day precipitation). We achieve this by leveraging a large ensemble (52 members) of high resolution (12 km) EURO-CORDEX simulations. The dataset will be of value, not only to the scientific community, but also practitioners in the public (e.g., municipal planners, government agencies) and private sectors (e.g., insurers and reinsurers).

UNASSIGNED: Analyzing genomic sequences plays a crucial role in understanding biological diversity and classifying Bamboo species. Existing methods for genomic sequence analysis suffer from limitations such as complexity, low accuracy, and the need for constant reconfiguration in response to evolving genomic datasets.
UNASSIGNED: This study addresses these limitations by introducing a novel Dual Heuristic Feature Selection-based Ensemble Classification Model (DHFS-ECM) for the precise identification of Bamboo species from genomic sequences.
UNASSIGNED: The proposed DHFS-ECM method employs a Genetic Algorithm to perform dual heuristic feature selection. This process maximizes inter-class variance, leading to the selection of informative N-gram feature sets. Subsequently, intra-class variance levels are used to create optimal training and validation sets, ensuring comprehensive coverage of class-specific features. The selected features are then processed through an ensemble classification layer, combining multiple stratification models for species-specific categorization.
UNASSIGNED: Comparative analysis with state-of-the-art methods demonstrate that DHFS-ECM achieves remarkable improvements in accuracy (9.5%), precision (5.9%), recall (8.5%), and AUC performance (4.5%). Importantly, the model maintains its performance even with an increased number of species classes due to the continuous learning facilitated by the Dual Heuristic Genetic Algorithm Model.
UNASSIGNED: DHFS-ECM offers several key advantages, including efficient feature extraction, reduced model complexity, enhanced interpretability, and increased robustness and accuracy through the ensemble classification layer. These attributes make DHFS-ECM a promising tool for real-time clinical applications and a valuable contribution to the field of genomic sequence analysis.

During the 2022-2023 unprecedented mpox epidemic, near real-time short-term forecasts of the epidemic\'s trajectory were essential in intervention implementation and guiding policy. However, as case levels have significantly decreased, evaluating model performance is vital to advancing the field of epidemic forecasting. Using laboratory-confirmed mpox case data from the Centers for Disease Control and Prevention and Our World in Data teams, we generated retrospective sequential weekly forecasts for Brazil, Canada, France, Germany, Spain, the United Kingdom, the United States and at the global scale using an auto-regressive integrated moving average (ARIMA) model, generalized additive model, simple linear regression, Facebook\'s Prophet model, as well as the sub-epidemic wave and n-sub-epidemic modelling frameworks. We assessed forecast performance using average mean squared error, mean absolute error, weighted interval scores, 95% prediction interval coverage, skill scores and Winkler scores. Overall, the n-sub-epidemic modelling framework outcompeted other models across most locations and forecasting horizons, with the unweighted ensemble model performing best most frequently. The n-sub-epidemic and spatial-wave frameworks considerably improved in average forecasting performance relative to the ARIMA model (greater than 10%) for all performance metrics. Findings further support sub-epidemic frameworks for short-term forecasting epidemics of emerging and re-emerging infectious diseases.

Despite achieving numerous successes with surface defect inspection based on deep learning, the industry still faces challenges in conducting packaging defect inspections that include critical information such as ingredient lists. In particular, while previous achievements primarily focus on defect inspection in high-quality images, they do not consider defect inspection in low-quality images such as those containing image blur. To address this issue, we proposed a noble inference technique named temporal-quality ensemble (TQE), which combines temporal and quality weights. Temporal weighting assigns weights to input images by considering the timing in relation to the observed image. Quality weight prioritizes high-quality images to ensure the inference process emphasizes clear and reliable input images. These two weights improve both the accuracy and reliability of the inference process of low-quality images. In addition, to experimentally evaluate the general applicability of TQE, we adopt widely used convolutional neural networks (CNNs) such as ResNet-34, EfficientNet, ECAEfficientNet, GoogLeNet, and ShuffleNetV2 as the backbone network. In conclusion, considering cases where at least one low-quality image is included, TQE has an F1-score approximately 17.64% to 22.41% higher than using single CNN models and about 1.86% to 2.06% higher than an average voting ensemble.