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The use of data generated passively by personal electronic devices, such as smartphones, to measure human function in health and disease has generated significant research interest. Particularly in psychiatry, objective, continuous quantitation using patients’ own devices may result in clinically useful markers that can be used to refine diagnostic processes, tailor treatment choices, improve condition monitoring for actionable outcomes, such as early signs of relapse, and develop new intervention models. If a principal goal for digital phenotyping is clinical improvement, research needs to attend now to factors that will help or hinder future clinical adoption. We identify four opportunities for research directed toward this goal: exploring intermediate outcomes and underlying disease mechanisms; focusing on purposes that are likely to be used in clinical practice; anticipating quality and safety barriers to adoption; and exploring the potential for digital personalized medicine arising from the integration of digital phenotyping and digital interventions. Clinical relevance also means explicitly addressing consumer needs, preferences, and acceptability as the ultimate users of digital phenotyping interventions. There is a risk that, without such considerations, the potential benefits of digital phenotyping are delayed or not realized because approaches that are feasible for application in healthcare, and the evidence required to support clinical commissioning, are not developed. Practical steps to accelerate this research agenda include the further development of digital phenotyping technology platforms focusing on scalability and equity, establishing shared data repositories and common data standards, and fostering multidisciplinary collaborations between clinical stakeholders (including patients), computer scientists, and researchers.

Video Question Answering (Video QA) challenges modelers in multiple fronts. Modeling video necessitates building not only spatio-temporal models for the dynamic visual channel but also multimodal structures for associated information channels such as subtitles or audio. Video QA adds at least two more layers of complexity – selecting relevant content for each channel in the context of the linguistic query, and composing spatio-temporal concepts and relations hidden in the data in response to the query. To address these requirements, we start with two insights: (a) content selection and relation construction can be jointly encapsulated into a conditional computational structure, and (b) video-length structures can be composed hierarchically. For (a) this paper introduces a general-reusable reusable neural unit dubbed Conditional Relation Network (CRN) taking as input a set of tensorial objects and translating into a new set of objects that encode relations of the inputs. The generic design of CRN helps ease the common complex model building process of Video QA by simple block stacking and rearrangements with flexibility in accommodating diverse input modalities and conditioning features across both visual and linguistic domains. As a result, we realize insight (b) by introducing Hierarchical Conditional Relation Networks (HCRN) for Video QA. The HCRN primarily aims at exploiting intrinsic properties of the visual content of a video as well as its accompanying channels in terms of compositionality, hierarchy, and near-term and far-term relation. HCRN is then applied for Video QA in two forms, short-form where answers are reasoned solely from the visual content of a video, and long-form where an additional associated information channel, such as movie subtitles, presented. Our rigorous evaluations show consistent improvements over state-of-the-art methods on well-studied benchmarks including large-scale real-world datasets such as TGIF-QA and TVQA, demonstrating the strong capabilities of our CRN unit and the HCRN for complex domains such as Video QA. To the best of our knowledge, the HCRN is the very first method attempting to handle long and short-form multimodal Video QA at the same time.

As more and more researchers are turning to big data for new opportunities of biomedical discoveries, machine learning models, as the backbone of big data analysis, are mentioned more often in biomedical journals. However, owing to the inherent complexity of machine learning methods, they are prone to misuse. Because of the flexibility in specifying machine learning models, the results are often insufficiently reported in research articles, hindering reliable assessment of model validity and consistent interpretation of model outputs. To attain a set of guidelines on the use of machine learning predictive models within clinical settings to make sure the models are correctly applied and sufficiently reported so that true discoveries can be distinguished from random coincidence. A multidisciplinary panel of machine learning experts, clinicians, and traditional statisticians were interviewed, using an iterative process in accordance with the Delphi method. The process produced a set of guidelines that consists of (1) a list of reporting items to be included in a research article and (2) a set of practical sequential steps for developing predictive models. A set of guidelines was generated to enable correct application of machine learning models and consistent reporting of model specifications and results in biomedical research. We believe that such guidelines will accelerate the adoption of big data analysis, particularly with machine learning methods, in the biomedical research community.

Entropy measures that assess signals' complexity have drawn increasing attention recently in biomedical field, as they have shown the ability of capturing unique features that are intrinsic and physiologically meaningful. In this study, we applied entropy analysis to electroencephalogram (EEG) data to examine its performance in epilepsy detection based on short-term EEG, aiming at establishing a short-term analysis protocol with optimal seizure detection performance. Two classification problems were considered, i.e., 1) classifying interictal and ictal EEGs (epileptic group) from normal EEGs; and 2) classifying ictal from interictal EEGs. For each problem, we explored two protocols to analyze the entropy of EEG: i) using a single analytical window with different window lengths, and ii) using an average of multiple windows for each window length. Two entropy methods-fuzzy entropy (FuzzyEn) and distribution entropy (DistEn)-were used that have valid outputs for any given data lengths. We performed feature selection and trained classifiers based on a cross-validation process. The results show that performance of FuzzyEn and DistEn may complement each other and the best performance can be achieved by combining: 1) FuzzyEn of one 5-s window and the averaged DistEn of five 1-s windows for classifying normal from epileptic group (accuracy: 0.93, sensitivity: 0.91, specificity: 0.96); and 2) the averaged FuzzyEn of five 1-s windows and DistEn of one 5-s window for classifying ictal from interictal EEGs (accuracy: 0.91, sensitivity: 0.93, specificity: 0.90). Further studies are warranted to examine whether this proposed short-term analysis procedure can help track the epileptic activities in real time and provide prompt feedback for clinical practices.

Background Technological advances in next-generation sequencing (NGS) and chromatographic assays [e.g., liquid chromatography mass spectrometry (LC-MS)] have made it possible to identify thousands of microbe and metabolite species, and to measure their relative abundance. In this paper, we propose a sparse neural encoder-decoder network to predict metabolite abundances from microbe abundances. Results Using paired data from a cohort of inflammatory bowel disease (IBD) patients, we show that our neural encoder-decoder model outperforms linear univariate and multivariate methods in terms of accuracy, sparsity, and stability. Importantly, we show that our neural encoder-decoder model is not simply a black box designed to maximize predictive accuracy. Rather, the network’s hidden layer (i.e., the latent space, comprised only of sparsely weighted microbe counts) actually captures key microbe-metabolite relationships that are themselves clinically meaningful. Although this hidden layer is learned without any knowledge of the patient’s diagnosis, we show that the learned latent features are structured in a way that predicts IBD and treatment status with high accuracy. Conclusions By imposing a non-negative weights constraint, the network becomes a directed graph where each downstream node is interpretable as the additive combination of the upstream nodes. Here, the middle layer comprises distinct microbe-metabolite axes that relate key microbial biomarkers with metabolite biomarkers. By pre-processing the microbiome and metabolome data using compositional data analysis methods, we ensure that our proposed multi-omics workflow will generalize to any pair of -omics data. To the best of our knowledge, this work is the first application of neural encoder-decoders for the interpretable integration of multi-omics biological data.

The discovery of processes for the synthesis of new materials involves many decisions about process design, operation, and material properties. Experimentation is crucial but as complexity increases, exploration of variables can become impractical using traditional combinatorial approaches. We describe an iterative method which uses machine learning to optimise process development, incorporating multiple qualitative and quantitative objectives. We demonstrate the method with a novel fluid processing platform for synthesis of short polymer fibers, and show how the synthesis process can be efficiently directed to achieve material and process objectives.

Data generated within social media platforms may present a new way to identify individuals who are experiencing mental illness. This study aimed to investigate the associations between linguistic features in individuals’ blog data and their symptoms of depression, generalised anxiety, and suicidal ideation. Individuals who blogged were invited to participate in a longitudinal study in which they completed fortnightly symptom scales for depression and anxiety (PHQ-9, GAD-7) for a period of 36 weeks. Blog data published in the same period was also collected, and linguistic features were analysed using the LIWC tool. Bivariate and multivariate analyses were performed to investigate the correlations between the linguistic features and symptoms between subjects. Multivariate regression models were used to predict longitudinal changes in symptoms within subjects. A total of 153 participants consented to the study. The final sample consisted of the 38 participants who completed the required number of symptom scales and generated blog data during the study period. Between-subject analysis revealed that the linguistic features “tentativeness” and “non-fluencies” were significantly correlated with symptoms of depression and anxiety, but not suicidal thoughts. Within-subject analysis showed no robust correlations between linguistic features and changes in symptoms. The findings may provide evidence of a relationship between some linguistic features in social media data and mental health; however, the study was limited by missing data and other important considerations. The findings also suggest that linguistic features observed at the group level may not generalise to, or be useful for, detecting individual symptom change over time.

Dimensionless groups quantify the balance among key forces governing a system’s physical behaviour and are foundational in engineering for describing, comparing, and scaling processes. By condensing complex system interactions into single values, they provide a powerful means of abstraction. Yet, their potential to actively guide process optimisation remains largely untapped. This study presents a framework that integrates dimensionless analysis with Bayesian optimisation to enhance both process performance and interpretability. Using this combined approach, we demonstrate that optimisation conducted in the dimensionless space not only accelerates convergence towards optimal process conditions but also reveals the underlying physical balances driving system behaviour. The method thus bridges data-driven optimisation with physically grounded understanding, enabling more efficient and explainable control of complex manufacturing processes.

Precision psychiatry is attracting increasing attention lately as a recognized priority. One of the goals of precision psychiatry is to develop tools capable of aiding a clinically informed psychiatric diagnosis objectively. Cognitive, inflammatory and immunological factors are altered in both bipolar disorder (BD) and schizophrenia (SZ), however, most of these alterations do not respect diagnostic boundaries from a phenomenological perspective and possess great variability in different individuals with the same phenotypic diagnosis and, consequently, none so far has proven to have the ability of reliably aiding in the differential diagnosis of BD and SZ. We developed a probabilistic multi-domain data integration model consisting of immune and inflammatory biomarkers in peripheral blood and cognitive biomarkers using machine learning to predict diagnosis of BD and SZ. A total of 416 participants, being 323, 372, and 279 subjects for blood, cognition and combined biomarkers analysis, respectively. Our multi-domain model performances for the BD vs. control (sensitivity 80% and specificity 71%) and for the SZ vs. control (sensitivity 84% and specificity 81%) pairs were high in general, however, our multi-domain model had only moderate performance for the differential diagnosis of BD and SZ (sensitivity 71% and specificity 73%). In conclusion, our results show that the diagnosis of BD and of SZ, and that the differential diagnosis of BD and SZ can be predicted with possible clinical utility by a computational machine learning algorithm employing blood and cognitive biomarkers, and that their integration in a multi-domain outperforms algorithms based in only one domain. Independent studies are needed to validate these findings.

Background Breast cancer is a collection of multiple tissue pathologies, each with a distinct molecular signature that correlates with patient prognosis and response to therapy. Accurately differentiating between breast cancer sub-types is an important part of clinical decision-making. Although this problem has been addressed using machine learning methods in the past, there remains unexplained heterogeneity within the established sub-types that cannot be resolved by the commonly used classification algorithms. Methods In this paper, we propose a novel deep learning architecture, called DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression), which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. We then perform a principal component analysis of these biomarker scores to visualise the sample heterogeneity, and use a linear model to test whether the major principal axes associate with known clinical phenotypes. Results Our model not only classifies cancer sub-types with good accuracy, but simultaneously assigns each patient their own set of interpretable and individualised biomarker scores. These personalised scores describe how important each feature is in the classification of any patient, and can be analysed post-hoc to generate new hypotheses about latent heterogeneity. Conclusions We apply the DeepTRIAGE framework to classify the gene expression signatures of luminal A and luminal B breast cancer sub-types, and illustrate its use for genes as well as the GO and KEGG gene sets. Using DeepTRIAGE , we calculate personalised biomarker scores that describe the most important features for classifying an individual patient as luminal A or luminal B. In doing so, DeepTRIAGE simultaneously reveals heterogeneity within the luminal A biomarker scores that significantly associate with tumour stage, placing all luminal samples along a continuum of severity.