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Paper spray ionization has been used as a fast sampling/ionization method for the direct mass spectrometric analysis of biological samples at ambient conditions. Here, we demonstrated that by utilizing paper spray ionization-mass spectrometry (PSI-MS) coupled with field asymmetric waveform ion mobility spectrometry (FAIMS), predictive metabolic and lipidomic profiles of routine breast core needle biopsies could be obtained effectively. By the combination of machine learning algorithms and pathological examination reports, we developed a classification model, which has an overall accuracy of 87.5% for an instantaneous differentiation between cancerous and noncancerous breast tissues utilizing metabolic and lipidomic profiles. Our results suggested that paper spray ionization-ion mobility spectrometry-mass spectrometry (PSI-IMS-MS) is a powerful approach for rapid breast cancer diagnosis based on altered metabolic and lipidomic profiles.

Many complex physical systems exhibit a rich variety of discrete behavioural modes. Often, the system complexity limits the applicability of standard modelling tools. Hence, understanding the underlying physics of different behaviours and distinguishing between them is challenging. Although traditional machine learning techniques could predict and classify behaviour well, typically they do not provide any meaningful insight into the underlying physics of the system. In this paper we present a novel method for extracting physically meaningful clusters of discrete behaviour from limited experimental observations. This method obtains a set of physically plausible functions that both facilitate behavioural clustering and aid in system understanding. We demonstrate the approach on the V-shaped falling paper system, a new falling paper type system that exhibits four distinct behavioural modes depending on a few morphological parameters. Using just 49 experimental observations, the method discovered a set of candidate functions that distinguish behaviours with an error of 2.04%, while also aiding insight into the physical phenomena driving each behaviour. © 2019 Howison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Motivation Drug repositioning is an attractive alternative to de novo drug discovery due to reduced time and costs to bring drugs to market. Computational repositioning methods, particularly non-black-box methods that can account for and predict a drug’s mechanism, may provide great benefit for directing future development. By tuning both data and algorithm to utilize relationships important to drug mechanisms, a computational repositioning algorithm can be trained to both predict and explain mechanistically novel indications. Results In this work, we examined the 123 curated drug mechanism paths found in the drug mechanism database (DrugMechDB) and after identifying the most important relationships, we integrated 18 data sources to produce a heterogeneous knowledge graph, MechRepoNet, capable of capturing the information in these paths. We applied the Rephetio repurposing algorithm to MechRepoNet using only a subset of relationships known to be mechanistic in nature and found adequate predictive ability on an evaluation set with AUROC value of 0.83. The resulting repurposing model allowed us to prioritize paths in our knowledge graph to produce a predicted treatment mechanism. We found that DrugMechDB paths, when present in the network were rated highly among predicted mechanisms. We then demonstrated MechRepoNet’s ability to use mechanistic insight to identify a drug’s mechanistic target, with a mean reciprocal rank of 0.525 on a test set of known drug–target interactions. Finally, we walked through repurposing examples of the anti-cancer drug imatinib for use in the treatment of asthma, and metolazone for use in the treatment of osteoporosis, to demonstrate this method’s utility in providing mechanistic insight into repurposing predictions it provides. Availability and implementation The Python code to reproduce the entirety of this analysis is available at: https://github.com/SuLab/MechRepoNet (archived at https://doi.org/10.5281/zenodo.6456335). Supplementary information Supplementary data are available at Bioinformatics online.

It is widely thought that individuals age at different rates. A method that measures “physiological age” or physiological aging rate independent of chronological age could therefore help elucidate mechanisms of aging and inform an individual’s risk of morbidity and mortality. Here we present machine learning frameworks for inferring individual physiological age from a broad range of biochemical and physiological traits including blood phenotypes (e.g., high-density lipoprotein), cardiovascular functions (e.g., pulse wave velocity) and psychological traits (e.g., neuroticism) as main groups in two population cohorts SardiNIA (~6,100 participants) and InCHIANTI (~1,400 participants). The inferred physiological age was highly correlated with chronological age (R2 > 0.8). We further defined an individual’s physiological aging rate (PAR) as the ratio of the predicted physiological age to the chronological age. Notably, PAR was a significant predictor of survival, indicating an effect of aging rate on mortality. Our trait-based PAR was correlated with DNA methylation-based epigenetic aging score (r = 0.6), suggesting that both scores capture a common aging process. PAR was also substantially heritable (h2~0.3), and a subsequent genome-wide association study of PAR identified significant associations with two genetic loci, one of which is implicated in telomerase activity. Our findings support PAR as a proxy for an underlying whole-body aging mechanism. PAR may thus be useful to evaluate the efficacy of treatments that target aging-related deficits and controllable epidemiological factors.

The process of aging and metabolism is intimately intertwined; thus, developing biomarkers related to metabolism is critical for delaying aging. However, few studies have identified reliable markers that reflect aging trajectories based on machine learning. We generated metabolomic profiles from rat urine using ultra-performance liquid chromatography/mass spectrometry. This was dynamically collected at four stages of the rat’s age (20, 50, 75, and 100 weeks) for both the training and test groups. Partial least squares-discriminant analysis score plots revealed a perfect separation trajectory in one direction with increasing age in the training and test groups. We further screened 25 aging-related biomarkers through the combination of four algorithms (VIP, time-series, LASSO, and SVM-RFE) in the training group. They were validated in the test group with an area under the curve of 1. Finally, six metabolites, known or novel aging-related markers, were identified, including epinephrine, glutarylcarnitine, L-kynurenine, taurine, 3-hydroxydodecanedioic acid, and N-acetylcitrulline. We also found that, except for N-acetylcitrulline (p < 0.05), the identified aging-related metabolites did not differ between tumor-free and tumor-bearing rats at 100 weeks (p > 0.05). Our findings reveal the metabolic trajectories of aging and provide novel biomarkers as potential therapeutic antiaging targets.

The prediction of poor ovarian response (POR) for stratified interference is a critical clinical issue that has received an increasing amount of recent concern. Anthropogenic diagnostic modes remain too simple for the handling of actual clinical complexity. Therefore, this study conducted extensive selection using models that were derived from a variety of machine learning algorithms, including random forest (RF), decision trees, eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), and artificial neural networks (ANN) for the development of two models called the COS pre-launch model (CPLM) and the hCG pre-trigger model (HPTM) to assess POR based on different requirements. The results demonstrated that CPLM constructed using ANN achieved the highest AUC result of all the algorithms in COS pre-launch (AUC=0.859, C-index=0.87, good calibration), and HPTL constructed using random forest was found to be the most effective in hCG pre-trigger (AUC=0.903, C-index=0.90, good calibration). It is notable that CPLM and HPTM exhibited better performance than common clinical characteristics (0.895 [CPLM], and 0.903 [HPTM] in comparison to 0.824 [anti-Müllerian hormone (AMH)], and 0.799 [antral follicle count (AFC)]). Furthermore, variable importance figure elucidated the values of AMH, AFC, and E2 level and follicle number on hCG day, which provides important theoretical guidance and experimental data for further application. Generally, the CPLM and HPTM can offer effective POR prediction for patients who are receiving assisted reproduction technology (ART), and has great potential for guiding the clinical treatment of infertility.

With the development of high-throughput sequencing technology, biological sequence data reflecting life information becomes increasingly accessible. Particularly on the background of the COVID-19 pandemic, biological sequence data play an important role in detecting diseases, analyzing the mechanism and discovering specific drugs. In recent years, pretraining models that have emerged in natural language processing have attracted widespread attention in many research fields not only to decrease training cost but also to improve performance on downstream tasks. Pretraining models are used for embedding biological sequence and extracting feature from large biological sequence corpus to comprehensively understand the biological sequence data. In this survey, we provide a broad review on pretraining models for biological sequence data. Moreover, we first introduce biological sequences and corresponding datasets, including brief description and accessible link. Subsequently, we systematically summarize popular pretraining models for biological sequences based on four categories: CNN, word2vec, LSTM and Transformer. Then, we present some applications with proposed pretraining models on downstream tasks to explain the role of pretraining models. Next, we provide a novel pretraining scheme for protein sequences and a multitask benchmark for protein pretraining models. Finally, we discuss the challenges and future directions in pretraining models for biological sequences.

Rationale: This paper aims to show how the focus on eradicating bias from Machine Learning decision-support systems in medical diagnosis diverts attention from the hermeneutic nature of medical decision-making and the productive role of bias. We want to show how an introduction of Machine Learning systems alters the diagnostic process. Reviewing the negative conception of bias and incorporating the mediating role of Machine Learning systems in the medical diagnosis are essential for an encompassing, critical and informed medical decision-making. Methods: This paper presents a philosophical analysis, employing the conceptual frameworks of hermeneutics and technological mediation, while drawing on the case of Machine Learning algorithms assisting doctors in diagnosis. This paper unravels the non-neutral role of algorithms in the doctor's decision-making and points to the dialogical nature of interaction not only with the patients but also with the technologies that co-shape the diagnosis. Findings: Following the hermeneutical model of medical diagnosis, we review the notion of bias to show how it is an inalienable and productive part of diagnosis. We show how Machine Learning biases join the human ones to actively shape the diagnostic process, simultaneously expanding and narrowing medical attention, highlighting certain aspects, while disclosing others, thus mediating medical perceptions and actions. Based on that, we demonstrate how doctors can take Machine Learning systems on board for an enhanced medical diagnosis, while being aware of their non-neutral role. Conclusions: We show that Machine Learning systems join doctors and patients in co-designing a triad of medical diagnosis. We highlight that it is imperative to examine the hermeneutic role of the Machine Learning systems. Additionally, we suggest including not only the patient, but also colleagues to ensure an encompassing diagnostic process, to respect its inherently hermeneutic nature and to work productively with the existing human and machine biases.

Rationale: The endemic of peri-implantitis affects over 25% of dental implants. Current treatment depends on empirical patient and site-based stratifications and lacks a consistent risk grading system. Methods: We investigated a unique cohort of peri-implantitis patients undergoing regenerative therapy with comprehensive clinical, immune, and microbial profiling. We utilized a robust outlier-resistant machine learning algorithm for immune deconvolution. Results: Unsupervised clustering identified risk groups with distinct immune profiles, microbial colonization dynamics, and regenerative outcomes. Low-risk patients exhibited elevated M1/M2-like macrophage ratios and lower B-cell infiltration. The low-risk immune profile was characterized by enhanced complement signaling and higher levels of Th1 and Th17 cytokines. Fusobacterium nucleatum and Prevotella intermedia were significantly enriched in high-risk individuals. Although surgery reduced microbial burden at the peri-implant interface in all groups, only low-risk individuals exhibited suppression of keystone pathogen re-colonization. Conclusion: Peri-implant immune microenvironment shapes microbial composition and the course of regeneration. Immune signatures show untapped potential in improving the risk-grading for peri-implantitis.

Early risk assessments and interventions for metabolic syndrome (MetS) are limited because of a lack of effective biomarkers. In the present study, several candidate genes were selected as a blood-based transcriptomic signature for MetS. We collected so far the largest MetS-associated peripheral blood high-throughput transcriptomics data and put forward a novel feature selection strategy by combining weighted gene co-expression network analysis, protein-protein interaction network analysis, LASSO regression and random forest approaches. Two gene modules and 51 hub genes as well as a 9-hub-gene signature associated with metabolic syndrome were identified. Then, based on this 9-hub-gene signature, we performed logistic analysis and subsequently established a web nomogram calculator for metabolic syndrome risk (https://xjtulgz.shinyapps.io/DynNomapp/). This 9-hub-gene signature showed excellent classification and calibration performance (AUC = 0.968 in training set, AUC = 0.883 in internal validation set, AUC = 0.861 in external validation set) as well as ideal potential clinical benefit.

Aims This study aimed to investigate changes of plasma cytokines and to develop machine learning classifiers for predicting non-proliferative diabetic retinopathy among type 2 diabetes mellitus patients. Results There were 12 plasma cytokines significantly higher in the non-proliferative diabetic retinopathy group in the pilot cohort. The validation cohort showed that angiopoietin 1, platelet-derived growth factor-BB, tissue inhibitors of metalloproteinase 2 and vascular endothelial growth factor receptor 2 were significantly higher in the NPDR group. Machine learning algorithms using the random forest yielded the best performance, with sensitivity of 92.3%, specificity of 75%, PPV of 82.8%, NPV of 88.2% and area under the curve of 0.84. Conclusions Plasma angiopoietin 1, platelet-derived growth factor-BB, and vascular endothelial growth factor receptor 2 were associated with presence of non-proliferative diabetic retinopathy and may be good biomarkers that play important roles in pathophysiology of diabetic retinopathy. Materials and methods In pilot cohort, 60 plasma cytokines were simultaneously measured. In validation cohort, angiopoietin 1, CXC-chemokine ligand 16, platelet-derived growth factor-BB, tissue inhibitors of metalloproteinase 1, tissue inhibitors of metalloproteinase 2, and vascular endothelial growth factor receptor 2 were validated using ELISA kits. Machine learning algorithms were developed to build a prediction model for non-proliferative diabetic retinopathy.

Background: Heterogeneity in Acute Respiratory Distress Syndrome (ARDS), as a consequence of its non-specific definition, has led to a multitude of negative randomised controlled trials (RCTs). Investigators have sought to identify heterogeneity of treatment effect (HTE) in RCTs using clustering algorithms. We evaluated the proficiency of several commonly-used machine-learning algorithms to identify clusters where HTE may be detected. Methods: Five unsupervised: Latent class analysis (LCA), K-means, partition around medoids, hierarchical, and spectral clustering; and four supervised algorithms: model-based recursive partitioning, Causal Forest (CF), and X-learner with Random Forest (XL-RF) and Bayesian Additive Regression Trees were individually applied to three prior ARDS RCTs. Clinical data and research protein biomarkers were used as partitioning variables, with the latter excluded for secondary analyses. For a clustering schema, HTE was evaluated based on the interaction term of treatment group and cluster with day-90 mortality as the dependent variable. Findings: No single algorithm identified clusters with significant HTE in all three trials. LCA, XL-RF, and CF identified HTE most frequently (2/3 RCTs). Important partitioning variables in the unsupervised approaches were consistent across algorithms and RCTs. In supervised models, important partitioning variables varied between algorithms and across RCTs. In algorithms where clusters demonstrated HTE in the same trial, patients frequently interchanged clusters from treatment-benefit to treatment-harm clusters across algorithms. LCA aside, results from all other algorithms were subject to significant alteration in cluster composition and HTE with random seed change. Removing research biomarkers as partitioning variables greatly reduced the chances of detecting HTE across all algorithms. Interpretation: Machine-learning algorithms were inconsistent in their abilities to identify clusters with significant HTE. Protein biomarkers were essential in identifying clusters with HTE. Investigations using machine-learning approaches to identify clusters to seek HTE require cautious interpretation. Funding: NIGMS R35 GM142992 (PS), NHLBI R35 HL140026 (CSC); NIGMS R01 GM123193, Department of Defense W81XWH-21-1-0009, NIA R21 AG068720, NIDA R01 DA051464 (MMC)

iQSPR is an inverse molecular design algorithm based on Bayesian inference that was developed in our previous study. Here, the algorithm is integrated in Python as a new module called iQSPR‐X in the all‐in‐one materials informatics platform XenonPy. Our new software provides a flexible, easy‐to‐use, and extensible platform for users to build customized molecular design algorithms using pre‐set modules and a pre‐trained model library in XenonPy. In this paper, we describe key features of iQSPR‐X and provide guidance on its use, illustrated by an application to a polymer design that targets a specific range of bandgap and dielectric constant.

Motivation Integration of data from different modalities is a necessary step for multi-scale data analysis in many fields, including biomedical research and systems biology. Directed graphical models offer an attractive tool for this problem because they can represent both the complex, multivariate probability distributions and the causal pathways influencing the system. Graphical models learned from biomedical data can be used for classification, biomarker selection and functional analysis, while revealing the underlying network structure and thus allowing for arbitrary likelihood queries over the data. Results In this paper, we present and test new methods for finding directed graphs over mixed data types (continuous and discrete variables). We used this new algorithm, CausalMGM, to identify variables directly linked to disease diagnosis and progression in various multi-modal datasets, including clinical datasets from chronic obstructive pulmonary disease (COPD). COPD is the third leading cause of death and a major cause of disability and thus determining the factors that cause longitudinal lung function decline is very important. Applied on a COPD dataset, mixed graphical models were able to confirm and extend previously described causal effects and provide new insights on the factors that potentially affect the longitudinal lung function decline of COPD patients. Availability and implementation The CausalMGM package is available on http://www.causalmgm.org. Supplementary information Supplementary data are available at Bioinformatics online.

Motivation The association analysis between genetic variants and imaging phenotypes must be carried out to understand the inherited neuropsychiatric disorders via imaging genetic studies. Given the high dimensionality in imaging and genetic data, traditional methods based on massive univariate regression entail large computational cost and disregard many-to-many correlations between phenotypes and genetic variants. Several multivariate imaging genetic methods have been proposed to alleviate the above problems. However, most of these methods are based on the l1 penalty, which might cause the over-selection of variables and thus mislead scientists in analyzing data from the field of neuroimaging genetics. Results To address these challenges in both statistics and computation, we propose a novel co-sparse reduced-rank regression model that identifies complex correlations in a dimensional reduction manner. We developed an iterative algorithm based on a group primal dual-active set formulation to detect simultaneously important genetic variants and imaging phenotypes efficiently and precisely via non-convex penalty. The simulation studies showed that our method achieved accurate and stable performance in parameter estimation and variable selection. In real application, the proposed approach successfully detected several novel Alzheimer’s disease-related genetic variants and regions of interest, which indicate that our method may be a valuable statistical toolbox for imaging genetic studies. Availability and implementation The R package csrrr, and the code for experiments in this article is available in Github: https://github.com/hailongba/csrrr. Supplementary information Supplementary data are available at Bioinformatics online.

Motivation Recent developments in technology have enabled researchers to collect multiple OMICS datasets for the same individuals. The conventional approach for understanding the relationships between the collected datasets and the complex trait of interest would be through the analysis of each OMIC dataset separately from the rest, or to test for associations between the OMICS datasets. In this work we show that integrating multiple OMICS datasets together, instead of analysing them separately, improves our understanding of their in-between relationships as well as the predictive accuracy for the tested trait. Several approaches have been proposed for the integration of heterogeneous and high-dimensional (p≫n) data, such as OMICS. The sparse variant of canonical correlation analysis (CCA) approach is a promising one that seeks to penalize the canonical variables for producing sparse latent variables while achieving maximal correlation between the datasets. Over the last years, a number of approaches for implementing sparse CCA (sCCA) have been proposed, where they differ on their objective functions, iterative algorithm for obtaining the sparse latent variables and make different assumptions about the original datasets. Results Through a comparative study we have explored the performance of the conventional CCA proposed by Parkhomenko et al., penalized matrix decomposition CCA proposed by Witten and Tibshirani and its extension proposed by Suo et al. The aforementioned methods were modified to allow for different penalty functions. Although sCCA is an unsupervised learning approach for understanding of the in-between relationships, we have twisted the problem as a supervised learning one and investigated how the computed latent variables can be used for predicting complex traits. The approaches were extended to allow for multiple (more than two) datasets where the trait was included as one of the input datasets. Both ways have shown improvement over conventional predictive models that include one or multiple datasets. Availability and implementation https://github.com/theorod93/sCCA. Supplementary information Supplementary data are available at Bioinformatics online.

Motivation Expert-labeled data are essential to train phenotyping algorithms for cohort identification. However expert labeling is time and labor intensive, and the costs remain prohibitive for scaling phenotyping to wider use-cases. Results We present an approach referred to as polar labeling (PL), to create silver standard for training machine learning (ML) for disease classification. We test the hypothesis that ML models trained on the silver standard created by applying PL on unlabeled patient records, are comparable in performance to the ML models trained on gold standard, created by clinical experts through manual review of patient records. We perform experimental validation using health records of 38 023 patients spanning six diseases. Our results demonstrate the superior performance of the proposed approach. Availability and implementation We provide a Python implementation of the algorithm and the Python code developed for this study on Github. Supplementary information Supplementary data are available at Bioinformatics online.

Motivation High correlation in expression between regulatory elements is a persistent obstacle for the reverse-engineering of gene regulatory networks. If two potential regulators have matching expression patterns, it becomes challenging to differentiate between them, thus increasing the risk of false positive identifications. Results To allow for gene regulation predictions of high confidence, we propose a novel method, the Linear Profile Likelihood (LiPLike), that assumes a regression model and iteratively searches for interactions that cannot be replaced by a linear combination of other predictors. To compare the performance of LiPLike with other available inference methods, we benchmarked LiPLike using three independent datasets from the Dialogue on Reverse Engineering Assessment and Methods 5 (DREAM5) network inference challenge. We found that LiPLike could be used to stratify predictions of other inference tools, and when applied to the predictions of DREAM5 participants, we observed an average improvement in accuracy of >140% compared to individual methods. Furthermore, LiPLike was able to independently predict networks better than all DREAM5 participants when applied to biological data. When predicting the Escherichia coli network, LiPLike had an accuracy of 0.38 for the top-ranked 100 interactions, whereas the corresponding DREAM5 consensus model yielded an accuracy of 0.11. Availability and implementation We made LiPLike available to the community as a Python toolbox, available at https://gitlab.com/Gustafsson-lab/liplike. We believe that LiPLike will be used for high confidence predictions in studies where individual model interactions are of high importance, and to remove false positive predictions made by other state-of-the-art gene–gene regulation prediction tools. Supplementary information Supplementary data are available at Bioinformatics online.

Motivation The use of human genome discoveries and other established factors to build an accurate risk prediction model is an essential step toward precision medicine. While multi-layer high-dimensional omics data provide unprecedented data resources for prediction studies, their corresponding analytical methods are much less developed. Results We present a multi-kernel penalized linear mixed model with adaptive lasso (MKpLMM), a predictive modeling framework that extends the standard linear mixed models widely used in genomic risk prediction, for multi-omics data analysis. MKpLMM can capture not only the predictive effects from each layer of omics data but also their interactions via using multiple kernel functions. It adopts a data-driven approach to select predictive regions as well as predictive layers of omics data, and achieves robust selection performance. Through extensive simulation studies, the analyses of PET-imaging outcomes from the Alzheimer’s Disease Neuroimaging Initiative study, and the analyses of 64 drug responses, we demonstrate that MKpLMM consistently outperforms competing methods in phenotype prediction. Availability and implementation The R-package is available at https://github.com/YaluWen/OmicPred. Supplementary information Supplementary data are available at Bioinformatics online.

Significance: Early detection of oral cancer is vital for high-risk patients, and machine learning-based automatic classification is ideal for disease screening. However, current datasets collected from high-risk populations are unbalanced and often have detrimental effects on the performance of classification. Aim: To reduce the class bias caused by data imbalance. Approach: We collected 3851 polarized white light cheek mucosa images using our customized oral cancer screening device. We use weight balancing, data augmentation, undersampling, focal loss, and ensemble methods to improve the neural network performance of oral cancer image classification with the imbalanced multi-class datasets captured from high-risk populations during oral cancer screening in low-resource settings. Results: By applying both data-level and algorithm-level approaches to the deep learning training process, the performance of the minority classes, which were difficult to distinguish at the beginning, has been improved. The accuracy of “premalignancy” class is also increased, which is ideal for screening applications. Conclusions: Experimental results show that the class bias induced by imbalanced oral cancer image datasets could be reduced using both data- and algorithm-level methods. Our study may provide an important basis for helping understand the influence of unbalanced datasets on oral cancer deep learning classifiers and how to mitigate.

Falls are unusual actions that cause a significant health risk among older people. The growing percentage of people of old age requires urgent development of fall detection and prevention systems. The emerging technology focuses on developing such systems to improve quality of life, especially for the elderly. A fall prevention system tries to predict and reduce the risk of falls. In contrast, a fall detection system observes the fall and generates a help notification to minimize the consequences of falls. A plethora of technical and review papers exist in the literature with a primary focus on fall detection. Similarly, several studies are relatively old, with a focus on wearables only, and use statistical and threshold-based approaches with a high false alarm rate. Therefore, this paper presents the latest research trends in fall detection and prevention systems using Machine Learning (ML) algorithms. It uses recent studies and analyzes datasets, age groups, ML algorithms, sensors, and location. Additionally, it provides a detailed discussion of the current trends of fall detection and prevention systems with possible future directions. This overview can help researchers understand the current systems and propose new methodologies by improving the highlighted issues. ispartof: SENSORS vol:21 issue:15 ispartof: location:Switzerland status: published

Knee Osteoarthritis (ΚΟΑ) is a degenerative joint disease of the knee that results from the progressive loss of cartilage. Due to KOA’s multifactorial nature and the poor understanding of its pathophysiology, there is a need for reliable tools that will reduce diagnostic errors made by clinicians. The existence of public databases has facilitated the advent of advanced analytics in KOA research however the heterogeneity of the available data along with the observed high feature dimensionality make this diagnosis task difficult. The objective of the present study is to provide a robust Feature Selection (FS) methodology that could: (i) handle the multidimensional nature of the available datasets and (ii) alleviate the defectiveness of existing feature selection techniques towards the identification of important risk factors which contribute to KOA diagnosis. For this aim, we used multidisciplinary data obtained from the Osteoarthritis Initiative database for individuals without or with KOA. The proposed fuzzy ensemble feature selection methodology aggregates the results of several FS algorithms (filter, wrapper and embedded ones) based on fuzzy logic. The effectiveness of the proposed methodology was evaluated using an extensive experimental setup that involved multiple competing FS algorithms and several well-known ML models. A 73.55 % classification accuracy was achieved by the best performing model (Random Forest classifier) on a group of twenty-one selected risk factors. Explainability analysis was finally performed to quantify the impact of the selected features on the model’s output thus enhancing our understanding of the rationale behind the decision-making mechanism of the best model.

Significance: Screening and early detection of oral potentially malignant lesions (OPMLs) are of great significance in reducing the mortality rates associated with head and neck malignancies. Intra-oral multispectral optical imaging of tissues in conjunction with cloud-based machine learning (CBML) can be used to detect oral precancers at the point-of-care (POC) and guide the clinician to the most malignant site for biopsy. Aim: Develop a bimodal multispectral imaging system (BMIS) combining tissue autofluorescence and diffuse reflectance (DR) for mapping changes in oxygenated hemoglobin (HbO2) absorption in the oral mucosa, quantifying tissue abnormalities, and guiding biopsies. Approach: The hand-held widefield BMIS consisting of LEDs emitting at 405, 545, 575, and 610 nm, 5MPx monochrome camera, and proprietary Windows-based software was developed for image capture, processing, and analytics. The DR image ratio (R610/R545) was compared with pathologic classification to develop a CBML algorithm for real-time assessment of tissue status at the POC. Results: Sensitivity of 97.5% and specificity of 92.5% were achieved for discrimination of OPML from patient normal in 40 sites, whereas 82% sensitivity and 96.6% specificity were obtained for discrimination of abnormal (OPML + SCC) in 89 sites. Site-specific algorithms derived for buccal mucosa (27 sites) showed improved sensitivity and specificity of 96.3% for discrimination of OPML from normal. Conclusions: Assessment of oral cancer risk is possible by mapping of HbO2 absorption in tissues, and the BMIS system developed appears to be suitable for biopsy guidance and early detection of oral cancers.

BackgroundDigital phenotyping and machine learning are currently being used to augment or even replace traditional analytic procedures in many domains, including health care. Given the heavy reliance on smartphones and mobile devices around the world, this readily available source of data is an important and highly underutilized source that has the potential to improve mental health risk prediction and prevention and advance mental health globally.ObjectiveThis study aimed to apply machine learning in an acute mental health setting for suicide risk prediction. This study uses a nascent approach, adding to existing knowledge by using data collected through a smartphone in place of clinical data, which have typically been collected from health care records.MethodsWe created a smartphone app called Strength Within Me, which was linked to Fitbit, Apple Health kit, and Facebook, to collect salient clinical information such as sleep behavior and mood, step frequency and count, and engagement patterns with the phone from a cohort of inpatients with acute mental health (n=66). In addition, clinical research interviews were used to assess mood, sleep, and suicide risk. Multiple machine learning algorithms were tested to determine the best fit.ResultsK-nearest neighbors (KNN; k=2) with uniform weighting and the Euclidean distance metric emerged as the most promising algorithm, with 68% mean accuracy (averaged over 10,000 simulations of splitting the training and testing data via 10-fold cross-validation) and an average area under the curve of 0.65. We applied a combined 5×2 F test to test the model performance of KNN against the baseline classifier that guesses training majority, random forest, support vector machine and logistic regression, and achieved F statistics of 10.7 (P=.009) and 17.6 (P=.003) for training majority and random forest, respectively, rejecting the null of performance being the same. Therefore, we have taken the first steps in prototyping a system that could continuously and accurately assess the risk of suicide via mobile devices.ConclusionsPredicting for suicidality is an underaddressed area of research to which this paper makes a useful contribution. This is part of the first generation of studies to suggest that it is feasible to utilize smartphone-generated user input and passive sensor data to generate a risk algorithm among inpatients at suicide risk. The model reveals fair concordance between phone-derived and research-generated clinical data, and with iterative development, it has the potential for accurate discriminant risk prediction. However, although full automation and independence of clinical judgment or input would be a worthy development for those individuals who are less likely to access specialist mental health services, and for providing a timely response in a crisis situation, the ethical and legal implications of such advances in the field of psychiatry need to be acknowledged.

Over the last few years more and more organ and idiosyncratic toxicities were linked to mitochondrial toxicity. Despite well‐established assays, such as the seahorse and Glucose/Galactose assay, an in silico approach to mitochondrial toxicity is still feasible, particularly when it comes to the assessment of large compound libraries. Therefore, in silico approaches could be very beneficial to indicate hazards early in the drug development pipeline. By combining multiple endpoints, we derived the largest so far published dataset on mitochondrial toxicity. A thorough data analysis shows that molecules causing mitochondrial toxicity can be distinguished by physicochemical properties. Finally, the combination of machine learning and structural alerts highlights the suitability for in silico risk assessment of mitochondrial toxicity.

©Andrea Ferrario, Burcu Demiray, Kristina Yordanova, Minxia Luo, Mike Martin. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 15.09.2020. BACKGROUND: Reminiscence is the act of thinking or talking about personal experiences that occurred in the past. It is a central task of old age that is essential for healthy aging, and it serves multiple functions, such as decision-making and introspection, transmitting life lessons, and bonding with others. The study of social reminiscence behavior in everyday life can be used to generate data and detect reminiscence from general conversations. OBJECTIVE: The aims of this original paper are to (1) preprocess coded transcripts of conversations in German of older adults with natural language processing (NLP), and (2) implement and evaluate learning strategies using different NLP features and machine learning algorithms to detect reminiscence in a corpus of transcripts. METHODS: The methods in this study comprise (1) collecting and coding of transcripts of older adults' conversations in German, (2) preprocessing transcripts to generate NLP features (bag-of-words models, part-of-speech tags, pretrained German word embeddings), and (3) training machine learning models to detect reminiscence using random forests, support vector machines, and adaptive and extreme gradient boosting algorithms. The data set comprises 2214 transcripts, including 109 transcripts with reminiscence. Due to class imbalance in the data, we introduced three learning strategies: (1) class-weighted learning, (2) a meta-classifier consisting of a voting ensemble, and (3) data augmentation with the Synthetic Minority Oversampling Technique (SMOTE) algorithm. For each learning strategy, we performed cross-validation on a random sample of the training data set of transcripts. We computed the area under the curve (AUC), the average precision (AP), precision, recall, as well as F1 score and specificity measures on the test data, for all combinations of NLP features, algorithms, and learning strategies. RESULTS: Class-weighted support vector machines on bag-of-words features outperformed all other classifiers (AUC=0.91, AP=0.56, precision=0.5, recall=0.45, F1=0.48, specificity=0.98), followed by support vector machines on SMOTE-augmented data and word embeddings features (AUC=0.89, AP=0.54, precision=0.35, recall=0.59, F1=0.44, specificity=0.94). For the meta-classifier strategy, adaptive and extreme gradient boosting algorithms trained on word embeddings and bag-of-words outperformed all other classifiers and NLP features; however, the performance of the meta-classifier learning strategy was lower compared to other strategies, with highly imbalanced precision-recall trade-offs. CONCLUSIONS: This study provides evidence of the applicability of NLP and machine learning pipelines for the automated detection of reminiscence in older adults' everyday conversations in German. The methods and findings of this study could be relevant for designing unobtrusive computer systems for the real-time detection of social reminiscence in the everyday life of older adults and classifying their functions. With further improvements, these systems could be deployed in health interventions aimed at improving older adults' well-being by promoting self-reflection and suggesting coping strategies to be used in the case of dysfunctional reminiscence cases, which can undermine physical and mental health., Journal of Medical Internet Research, 22 (9), ISSN:1438-8871

In this paper, we applied a novel method for the detection of Alzheimer's disease (AD) based on a structural magnetic resonance imaging (sMRI) dataset. Specifically, the method involved a new classification algorithm of machine learning, named Generalized Split Linearized Bregman Iteration (GSplit LBI). It combines logistic regression and structural sparsity regularizations. In the study, 57 AD patients and 47 normal controls (NCs) were enrolled. We first extracted the entire brain gray matter volume values of all subjects and then used GSplit LBI to build a predictive classification model with a 10-fold full cross-validation method. The model accuracy achieved 90.44%. To further verify which voxels in the dataset have greater impact on the prediction results, we ranked the weight parameters and obtained the top 6% of the model parameters. To verify the generalization of model prediction and the stability of feature selection, we performed a cross-test on the Alzheimer's Disease Neuroimaging Initiative (ADNI) and a Chinese dataset and achieved good performances on different cohorts. Conclusively, based on the sMRI dataset, our algorithm not only had good performance in a local cohort with high accuracy but also had good generalization of model prediction and stability of feature selection in different cohorts.

The increasing demand for smart vehicles with many sensing capabilities will escalate data traffic in vehicular networks. Meanwhile, available network resources are limited. The emergence of AI implementation in vehicular network resource allocation opens the opportunity to improve resource utilization to provide more reliable services. Accordingly, many resource allocation schemes with various machine learning algorithms have been proposed to dynamically manage and allocate network resources. This survey paper presents how machine learning is leveraged in the vehicular network resource allocation strategy. We focus our study on determining its role in the mechanism. First, we provide an analysis of how authors designed their scenarios to orchestrate the resource allocation strategy. Secondly, we classify the mechanisms based on the parameters they chose when designing the algorithms. Finally, we analyze the challenges in designing a resource allocation strategy in vehicular networks using machine learning. Therefore, a thorough understanding of how machine learning algorithms are utilized to offer a dynamic resource allocation in vehicular networks is provided in this study.

Background Ear and mastoid disease can easily be treated by early detection and appropriate medical care. However, short of specialists and relatively low diagnostic accuracy calls for a new way of diagnostic strategy, in which deep learning may play a significant role. The current study presents a machine learning model to automatically diagnose ear disease using a large database of otoendoscopic images acquired in the clinical environment. Methods Total 10,544 otoendoscopic images were used to train nine public convolution-based deep neural networks to classify eardrum and external auditory canal features into six categories of ear diseases, covering most ear diseases (Normal, Attic retraction, Tympanic perforation, Otitis externa±myringitis, Tumor). After evaluating several optimization schemes, two best-performing models were selected to compose an ensemble classifier, by combining classification scores of each classifier. Findings According to accuracy and training time, transfer learning models based on Inception-V3 and ResNet101 were chosen and the ensemble classifier using the two models yielded a significant improvement over each model, the accuracy of which is in average 93·67% for the 5-folds cross-validation. Considering substantial data-size dependency of classifier performance in the transfer learning, evaluated in this study, the high accuracy in the current model is attributable to the large database. Interpretation The current study is unprecedented in terms of both disease diversity and diagnostic accuracy, which is compatible or even better than an average otolaryngologist. The classifier was trained with data in a various acquisition condition, which is suitable for the practical environment. This study shows the usefulness of utilizing a deep learning model in the early detection and treatment of ear disease in the clinical situation. Fund This research was supported by Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT ( NRF-2017M3C7A1049051 ).

Motivation Validation of variable selection and predictive performance is crucial in construction of robust multivariate models that generalize well, minimize overfitting and facilitate interpretation of results. Inappropriate variable selection leads instead to selection bias, thereby increasing the risk of model overfitting and false positive discoveries. Although several algorithms exist to identify a minimal set of most informative variables (i.e. the minimal-optimal problem), few can select all variables related to the research question (i.e. the all-relevant problem). Robust algorithms combining identification of both minimal-optimal and all-relevant variables with proper cross-validation are urgently needed. Results We developed the MUVR algorithm to improve predictive performance and minimize overfitting and false positives in multivariate analysis. In the MUVR algorithm, minimal variable selection is achieved by performing recursive variable elimination in a repeated double cross-validation (rdCV) procedure. The algorithm supports partial least squares and random forest modelling, and simultaneously identifies minimal-optimal and all-relevant variable sets for regression, classification and multilevel analyses. Using three authentic omics datasets, MUVR yielded parsimonious models with minimal overfitting and improved model performance compared with state-of-the-art rdCV. Moreover, MUVR showed advantages over other variable selection algorithms, i.e. Boruta and VSURF, including simultaneous variable selection and validation scheme and wider applicability. Availability and implementation Algorithms, data, scripts and tutorial are open source and available as an R package (‘MUVR’) at https://gitlab.com/CarlBrunius/MUVR.git. Supplementary information Supplementary data are available at Bioinformatics online.

Motivation Drug repurposing is a potential alternative to the classical drug discovery pipeline. Repurposing involves finding novel indications for already approved drugs. In this work, we present a novel machine learning-based method for drug repurposing. This method explores the anti-similarity between drugs and a disease to uncover new uses for the drugs. More specifically, our proposed method takes into account three sources of information: (i) large-scale gene expression profiles corresponding to human cell lines treated with small molecules, (ii) gene expression profile of a human disease and (iii) the known relationship between Food and Drug Administration (FDA)-approved drugs and diseases. Using these data, our proposed method learns a similarity metric through a supervised machine learning-based algorithm such that a disease and its associated FDA-approved drugs have smaller distance than the other disease-drug pairs. Results We validated our framework by showing that the proposed method incorporating distance metric learning technique can retrieve FDA-approved drugs for their approved indications. Once validated, we used our approach to identify a few strong candidates for repurposing. Availability and implementation The R scripts are available on demand from the authors. Supplementary information Supplementary data are available at Bioinformatics online.

Motivation Network inference algorithms aim to uncover key regulatory interactions governing cellular decision-making, disease progression and therapeutic interventions. Having an accurate blueprint of this regulation is essential for understanding and controlling cell behavior. However, the utility and impact of these approaches are limited because the ways in which various factors shape inference outcomes remain largely unknown. Results We identify and systematically evaluate determinants of performance—including network properties, experimental design choices and data processing—by developing new metrics that quantify confidence across algorithms in comparable terms. We conducted a multifactorial analysis that demonstrates how stimulus target, regulatory kinetics, induction and resolution dynamics, and noise differentially impact widely used algorithms in significant and previously unrecognized ways. The results show how even if high-quality data are paired with high-performing algorithms, inferred models are sometimes susceptible to giving misleading conclusions. Lastly, we validate these findings and the utility of the confidence metrics using realistic in silico gene regulatory networks. This new characterization approach provides a way to more rigorously interpret how algorithms infer regulation from biological datasets. Availability and implementation Code is available at http://github.com/bagherilab/networkinference/. Supplementary information Supplementary data are available at Bioinformatics online.

MotivationRecent sequence-based analyses have identified a lot of gene variants that may contribute to neurogenetic disorders such as autism spectrum disorder and schizophrenia. Several state-of-the-art network-based analyses have been proposed for mechanical understanding of genetic variants in neurogenetic disorders. However, these methods were mainly designed for modeling and analyzing single networks that do not interact with or depend on other networks, and thus cannot capture the properties between interdependent systems in brain-specific tissues, circuits, and regions which are connected each other and affect behavior and cognitive processes.ResultsWe introduce a novel and efficient framework, called a “Network of Networks” (NoN) approach, to infer the interconnectivity structure between multiple networks where the response and the predictor variables are topological information matrices of given networks. We also propose Graph-Oriented SParsE Learning (GOSPEL), a new sparse structural learning algorithm for network graph data to identify a subset of the topological information matrices of the predictors related to the response. We demonstrate on simulated data that GOSPEL outperforms existing kernel-based algorithms in terms of F-measure. On real data from human brain region-specific functional networks associated with the autism risk genes, we show that the NoN model provides insights on the autism-associated interconnectivity structure between functional interaction networks and a comprehensive understanding of the genetic basis of autism across diverse regions of the brain.AvailabilityOur software is available from https://github.com/infinite-point/GOSPEL.Contactkawakubo@med.nagoya-u.ac.jp, shimamura@med.nagoya-u.ac.jpSupplementary informationSupplementary data are available at Bioinformatics online.

Motivation Precision medicine is an emerging field with hopes to improve patient treatment and reduce morbidity and mortality. To these ends, computational approaches have predicted associations among genes, chemicals and diseases. Such efforts, however, were often limited to using just some available association types. This lowers prediction coverage and, since prior evidence shows that integrating heterogeneous data is likely beneficial, it may limit accuracy. Therefore, we systematically tested whether using more association types improves prediction. Results We study multimodal networks linking diseases, genes and chemicals (drugs) by applying three diffusion algorithms and varying information content. Ten-fold cross-validation shows that these networks are internally consistent, both within and across association types. Also, diffusion methods recovered missing edges, even if all the edges from an entire mode of association were removed. This suggests that information is transferable between these association types. As a realistic validation, time-stamped experiments simulated the predictions of future associations based solely on information known prior to a given date. The results show that many future published results are predictable from current associations. Moreover, in most cases, using more association types increases prediction coverage without significantly decreasing sensitivity and specificity. In case studies, literature-supported validation shows that these predictions mimic human-formulated hypotheses. Overall, this study suggests that diffusion over a more comprehensive multimodal network will generate more useful hypotheses of associations among diseases, genes and chemicals, which may guide the development of precision therapies. Availability and implementation Code and data are available at https://github.com/LichtargeLab/multimodal-network-diffusion. Supplementary information Supplementary data are available at Bioinformatics online.

This study presents an application of machine learning (ML) methods for detecting the presence of stenoses and aneurysms in the human arterial system. Four major forms of arterial disease -- carotid artery stenosis (CAS), subclavian artery stenosis (SAC), peripheral arterial disease (PAD), and abdominal aortic aneurysms (AAA) -- are considered. The ML methods are trained and tested on a physiologically realistic virtual patient database (VPD) containing 28,868 healthy subjects, which is adapted from the authors previous work and augmented to include the four disease forms. Six ML methods -- Naive Bayes, Logistic Regression, Support Vector Machine, Multi-layer Perceptron, Random Forests, and Gradient Boosting -- are compared with respect to classification accuracies and it is found that the tree-based methods of Random Forest and Gradient Boosting outperform other approaches. The performance of ML methods is quantified through the F1 score and computation of sensitivities and specificities. When using all the six measurements, it is found that maximum F1 scores larger than 0.9 are achieved for CAS and PAD, larger than 0.85 for SAS, and larger than 0.98 for both low- and high-severity AAAs. Corresponding sensitivities and specificities are larger than 90% for CAS and PAD, larger than 85% for SAS, and larger than 98% for both low- and high-severity AAAs. When reducing the number of measurements, it is found that the performance is degraded by less than 5% when three measurements are used, and less than 10% when only two measurements are used for classification. For AAA, it is shown that F1 scores larger than 0.85 and corresponding sensitivities and specificities larger than 85% are achievable when using only a single measurement. The results are encouraging to pursue AAA monitoring and screening through wearable devices which can reliably measure pressure or flow-rates, Changelog: Added a bullet point in the discussion (end of section 3.3)

Background The dataset from genes used to predict hepatitis C virus outcome was evaluated in a previous study using a conventional statistical methodology. Objective The aim of this study was to reanalyze this same dataset using the data mining approach in order to find models that improve the classification accuracy of the genes studied. Methods We built predictive models using different subsets of factors, selected according to their importance in predicting patient classification. We then evaluated each independent model and also a combination of them, leading to a better predictive model. Results Our data mining approach identified genetic patterns that escaped detection using conventional statistics. More specifically, the partial decision trees and ensemble models increased the classification accuracy of hepatitis C virus outcome compared with conventional methods. Conclusions Data mining can be used more extensively in biomedicine, facilitating knowledge building and management of human diseases.

Background One of the major challenges in the health care sector is that approximately 80% of generated data remains unstructured and unused. Since it is difficult to handle unstructured data from electronic medical record systems, it tends to be neglected for analyses in most hospitals and medical centers. Therefore, there is a need to analyze unstructured big data in health care systems so that we can optimally utilize and unearth all unexploited information from it. Objective In this study, we aimed to extract a list of diseases and associated keywords along with the corresponding time durations from an indigenously developed electronic medical record system and describe the possibility of analytics from the acquired datasets. Methods We propose a novel, finite-state machine to sequentially detect and cluster disease names from patients’ medical history. We defined 3 states in the finite-state machine and transition matrix, which depend on the identified keyword. In addition, we also defined a state-change action matrix, which is essentially an action associated with each transition. The dataset used in this study was obtained from an indigenously developed electronic medical record system called eyeSmart that was implemented across a large, multitier ophthalmology network in India. The dataset included patients’ past medical history and contained records of 10,000 distinct patients. Results We extracted disease names and associated keywords by using the finite-state machine with an accuracy of 95%, sensitivity of 94.9%, and positive predictive value of 100%. For the extraction of the duration of disease, the machine’s accuracy was 93%, sensitivity was 92.9%, and the positive predictive value was 100%. Conclusions We demonstrated that the finite-state machine we developed in this study can be used to accurately identify disease names, associated keywords, and time durations from a large cohort of patient records obtained using an electronic medical record system.

Significance: Melanoma is a deadly cancer that physicians struggle to diagnose early because they lack the knowledge to differentiate benign from malignant lesions. Deep machine learning approaches to image analysis offer promise but lack the transparency to be widely adopted as stand-alone diagnostics. Aim: We aimed to create a transparent machine learning technology (i.e., not deep learning) to discriminate melanomas from nevi in dermoscopy images and an interface for sensory cue integration. Approach: Imaging biomarker cues (IBCs) fed ensemble machine learning classifier (Eclass) training while raw images fed deep learning classifier training. We compared the areas under the diagnostic receiver operator curves. Results: Our interpretable machine learning algorithm outperformed the leading deep-learning approach 75% of the time. The user interface displayed only the diagnostic imaging biomarkers as IBCs. Conclusions: From a translational perspective, Eclass is better than convolutional machine learning diagnosis in that physicians can embrace it faster than black box outputs. Imaging biomarkers cues may be used during sensory cue integration in clinical screening. Our method may be applied to other image-based diagnostic analyses, including pathology and radiology.

Motivation The recently proposed knockoff filter is a general framework for controlling the false discovery rate (FDR) when performing variable selection. This powerful new approach generates a ‘knockoff’ of each variable tested for exact FDR control. Imitation variables that mimic the correlation structure found within the original variables serve as negative controls for statistical inference. Current applications of knockoff methods use linear regression models and conduct variable selection only for variables existing in model functions. Here, we extend the use of knockoffs for machine learning with boosted trees, which are successful and widely used in problems where no prior knowledge of model function is required. However, currently available importance scores in tree models are insufficient for variable selection with FDR control. Results We propose a novel strategy for conducting variable selection without prior model topology knowledge using the knockoff method with boosted tree models. We extend the current knockoff method to model-free variable selection through the use of tree-based models. Additionally, we propose and evaluate two new sampling methods for generating knockoffs, namely the sparse covariance and principal component knockoff methods. We test and compare these methods with the original knockoff method regarding their ability to control type I errors and power. In simulation tests, we compare the properties and performance of importance test statistics of tree models. The results include different combinations of knockoffs and importance test statistics. We consider scenarios that include main-effect, interaction, exponential and second-order models while assuming the true model structures are unknown. We apply our algorithm for tumor purity estimation and tumor classification using Cancer Genome Atlas (TCGA) gene expression data. Our results show improved discrimination between difficult-to-discriminate cancer types. Availability and implementation The proposed algorithm is included in the KOBT package, which is available at https://cran.r-project.org/web/packages/KOBT/index.html. Supplementary information Supplementary data are available at Bioinformatics online.

Background The rapid spread of COVID-19 means that government and health services providers have little time to plan and design effective response policies. It is therefore important to quickly provide accurate predictions of how vulnerable geographic regions such as counties are to the spread of this virus. Objective The aim of this study is to develop county-level prediction around near future disease movement for COVID-19 occurrences using publicly available data. Methods We estimated county-level COVID-19 occurrences for the period March 14 to 31, 2020, based on data fused from multiple publicly available sources inclusive of health statistics, demographics, and geographical features. We developed a three-stage model using XGBoost, a machine learning algorithm, to quantify the probability of COVID-19 occurrence and estimate the number of potential occurrences for unaffected counties. Finally, these results were combined to predict the county-level risk. This risk was then used as an estimated after-five-day-vulnerability of the county. Results The model predictions showed a sensitivity over 71% and specificity over 94% for models built using data from March 14 to 31, 2020. We found that population, population density, percentage of people aged >70 years, and prevalence of comorbidities play an important role in predicting COVID-19 occurrences. We observed a positive association at the county level between urbanicity and vulnerability to COVID-19. Conclusions The developed model can be used for identification of vulnerable counties and potential data discrepancies. Limited testing facilities and delayed results introduce significant variation in reported cases, which produces a bias in the model.

Background Sequential information in electronic medical records is valuable and helpful for patient outcome prediction but is rarely used for patient similarity measurement because of its unevenness, irregularity, and heterogeneity. Objective We aimed to develop a patient similarity framework for patient outcome prediction that makes use of sequential and cross-sectional information in electronic medical record systems. Methods Sequence similarity was calculated from timestamped event sequences using edit distance, and trend similarity was calculated from time series using dynamic time warping and Haar decomposition. We also extracted cross-sectional information, namely, demographic, laboratory test, and radiological report data, for additional similarity calculations. We validated the effectiveness of the framework by constructing k–nearest neighbors classifiers to predict mortality and readmission for acute myocardial infarction patients, using data from (1) a public data set and (2) a private data set, at 3 time points—at admission, on Day 7, and at discharge—to provide early warning patient outcomes. We also constructed state-of-the-art Euclidean-distance k–nearest neighbor, logistic regression, random forest, long short-term memory network, and recurrent neural network models, which were used for comparison. Results With all available information during a hospitalization episode, predictive models using the similarity model outperformed baseline models based on both public and private data sets. For mortality predictions, all models except for the logistic regression model showed improved performances over time. There were no such increasing trends in predictive performances for readmission predictions. The random forest and logistic regression models performed best for mortality and readmission predictions, respectively, when using information from the first week after admission. Conclusions For patient outcome predictions, the patient similarity framework facilitated sequential similarity calculations for uneven electronic medical record data and helped improve predictive performance.

How to improve the prediction accuracy of RNA secondary structure is currently a hot topic. The existing prediction methods for a single sequence do not fully consider the folding diversity which may occur among RNAs with different functions or sources. This paper explores the relationship between folding diversity and prediction accuracy, and puts forward a new method to improve the prediction accuracy of RNA secondary structure. Our research investigates the following: 1. The folding feature based on stochastic context-free grammar is proposed. By using dimension reduction and clustering techniques, some public data sets are analyzed. The results show that there is significant folding diversity among different RNA families. 2. To assign folding rules to RNAs without structural information, a classification method based on production probability is proposed. The experimental results show that the classification method proposed in this paper can effectively classify the RNAs of unknown structure. 3. Based on the existing prediction methods of statistical learning models, an RNA secondary structure prediction framework is proposed, namely "Cluster - Training - Parameter Selection - Prediction". The results show that, with information on folding diversity, prediction accuracy can be significantly improved.

Protein flexibility and solvation pose major challenges to docking algorithms and scoring functions. One established strategy for addressing these challenges is to use multiple protein conformations for docking (all‐against‐all ensemble docking). Recent studies have shown that the performance of ensemble docking can be improved by selecting the most relevant protein structures for docking. In search for a robust approach to protein structure selection, we have come up with an integrated mAchine Learning AnD DockINg approach (ALADDIN). ALADDIN employs a battery of random forest classifiers to select, individually for each compound of interest, from an ensemble of protein structures, the single most suitable protein structure for docking. ALADDIN outperformed the best single‐structure docking runs, ensemble docking and a similarity‐based docking approach on three out of four investigated targets, with up to 0.15, 0.11 and 0.16 higher area under the receiver operating characteristic curve (AUC) values, respectively. Only in the case of cytochrome P450 3A4, ALADDIN, like any of the other tested approaches, failed to obtain decent performance. ALADDIN can be particularly useful for structure‐based virtual screening of malleable proteins, including kinases, some viral enzymes and anti‐targets. publishedVersion

Background Semisupervised and unsupervised anomaly detection methods have been widely used in various applications to detect anomalous objects from a given data set. Specifically, these methods are popular in the medical domain because of their suitability for applications where there is a lack of a sufficient data set for the other classes. Infection incidence often brings prolonged hyperglycemia and frequent insulin injections in people with type 1 diabetes, which are significant anomalies. Despite these potentials, there have been very few studies that focused on detecting infection incidences in individuals with type 1 diabetes using a dedicated personalized health model. Objective This study aims to develop a personalized health model that can automatically detect the incidence of infection in people with type 1 diabetes using blood glucose levels and insulin-to-carbohydrate ratio as input variables. The model is expected to detect deviations from the norm because of infection incidences considering elevated blood glucose levels coupled with unusual changes in the insulin-to-carbohydrate ratio. Methods Three groups of one-class classifiers were trained on target data sets (regular days) and tested on a data set containing both the target and the nontarget (infection days). For comparison, two unsupervised models were also tested. The data set consists of high-precision self-recorded data collected from three real subjects with type 1 diabetes incorporating blood glucose, insulin, diet, and events of infection. The models were evaluated on two groups of data: raw and filtered data and compared based on their performance, computational time, and number of samples required. Results The one-class classifiers achieved excellent performance. In comparison, the unsupervised models suffered from performance degradation mainly because of the atypical nature of the data. Among the one-class classifiers, the boundary and domain-based method produced a better description of the data. Regarding the computational time, nearest neighbor, support vector data description, and self-organizing map took considerable training time, which typically increased as the sample size increased, and only local outlier factor and connectivity-based outlier factor took considerable testing time. Conclusions We demonstrated the applicability of one-class classifiers and unsupervised models for the detection of infection incidence in people with type 1 diabetes. In this patient group, detecting infection can provide an opportunity to devise tailored services and also to detect potential public health threats. The proposed approaches achieved excellent performance; in particular, the boundary and domain-based method performed better. Among the respective groups, particular models such as one-class support vector machine, K-nearest neighbor, and K-means achieved excellent performance in all the sample sizes and infection cases. Overall, we foresee that the results could encourage researchers to examine beyond the presented features into other additional features of the self-recorded data, for example, continuous glucose monitoring features and physical activity data, on a large scale.

Background As the need for sharing genomic data grows, privacy issues and concerns, such as the ethics surrounding data sharing and disclosure of personal information, are raised. Objective The main purpose of this study was to verify whether genomic data is sufficient to predict a patient's personal information. Methods RNA expression data and matched patient personal information were collected from 9538 patients in The Cancer Genome Atlas program. Five personal information variables (age, gender, race, cancer type, and cancer stage) were recorded for each patient. Four different machine learning algorithms (support vector machine, decision tree, random forest, and artificial neural network) were used to determine whether a patient's personal information could be accurately predicted from RNA expression data. Performance measurement of the prediction models was based on the accuracy and area under the receiver operating characteristic curve. We selected five cancer types (breast carcinoma, kidney renal clear cell carcinoma, head and neck squamous cell carcinoma, low-grade glioma, and lung adenocarcinoma) with large samples sizes to verify whether predictive accuracy would differ between them. We also validated the efficacy of our four machine learning models in analyzing normal samples from 593 cancer patients. Results In most samples, personal information with high genetic relevance, such as gender and cancer type, could be predicted from RNA expression data alone. The prediction accuracies for gender and cancer type, which were the best models, were 0.93-0.99 and 0.78-0.94, respectively. Other aspects of personal information, such as age, race, and cancer stage, were difficult to predict from RNA expression data, with accuracies ranging from 0.0026-0.29, 0.76-0.96, and 0.45-0.79, respectively. Among the tested machine learning methods, the highest predictive accuracy was obtained using the support vector machine algorithm (mean accuracy 0.77), while the lowest accuracy was obtained using the random forest method (mean accuracy 0.65). Gender and race were predicted more accurately than other variables in the samples. On average, the accuracy of cancer stage prediction ranged between 0.71-0.67, while the age prediction accuracy ranged between 0.18-0.23 for the five cancer types. Conclusions We attempted to predict patient information using RNA expression data. We found that some identifiers could be predicted, but most others could not. This study showed that personal information available from RNA expression data is limited and this information cannot be used to identify specific patients.

Background SymptomGuide Dementia (DGI Clinical Inc) is a publicly available online symptom tracking tool to support caregivers of persons living with dementia. The value of such data are enhanced when the specific dementia stage is identified. Objective We aimed to develop a supervised machine learning algorithm to classify dementia stages based on tracked symptoms. Methods We employed clinical data from 717 people from 3 sources: (1) a memory clinic; (2) long-term care; and (3) an open-label trial of donepezil in vascular and mixed dementia (VASPECT). Symptoms were captured with SymptomGuide Dementia. A clinician classified participants into 4 groups using either the Functional Assessment Staging Test or the Global Deterioration Scale as mild cognitive impairment, mild dementia, moderate dementia, or severe dementia. Individualized symptom profiles from the pooled data were used to train machine learning models to predict dementia severity. Models trained with 6 different machine learning algorithms were compared using nested cross-validation to identify the best performing model. Model performance was assessed using measures of balanced accuracy, precision, recall, Cohen κ, area under the receiver operating characteristic curve (AUROC), and area under the precision-recall curve (AUPRC). The best performing algorithm was used to train a model optimized for balanced accuracy. Results The study population was mostly female (424/717, 59.1%), older adults (mean 77.3 years, SD 10.6, range 40-100) with mild to moderate dementia (332/717, 46.3%). Age, duration of symptoms, 37 unique dementia symptoms, and 10 symptom-derived variables were used to distinguish dementia stages. A model trained with a support vector machine learning algorithm using a one-versus-rest approach showed the best performance. The correct dementia stage was identified with 83% balanced accuracy (Cohen κ=0.81, AUPRC 0.91, AUROC 0.96). The best performance was seen when classifying severe dementia (AUROC 0.99). Conclusions A supervised machine learning algorithm exhibited excellent performance in identifying dementia stages based on dementia symptoms reported in an online environment. This novel dementia staging algorithm can be used to describe dementia stage based on user-reported symptoms. This type of symptom recording offers real-world data that reflect important symptoms in people with dementia.

Background Supervised machine learning (ML) is being featured in the health care literature with study results frequently reported using metrics such as accuracy, sensitivity, specificity, recall, or F1 score. Although each metric provides a different perspective on the performance, they remain to be overall measures for the whole sample, discounting the uniqueness of each case or patient. Intuitively, we know that all cases are not equal, but the present evaluative approaches do not take case difficulty into account. Objective A more case-based, comprehensive approach is warranted to assess supervised ML outcomes and forms the rationale for this study. This study aims to demonstrate how the item response theory (IRT) can be used to stratify the data based on how difficult each case is to classify, independent of the outcome measure of interest (eg, accuracy). This stratification allows the evaluation of ML classifiers to take the form of a distribution rather than a single scalar value. Methods Two large, public intensive care unit data sets, Medical Information Mart for Intensive Care III and electronic intensive care unit, were used to showcase this method in predicting mortality. For each data set, a balanced sample (n=8078 and n=21,940, respectively) and an imbalanced sample (n=12,117 and n=32,910, respectively) were drawn. A 2-parameter logistic model was used to provide scores for each case. Several ML algorithms were used in the demonstration to classify cases based on their health-related features: logistic regression, linear discriminant analysis, K-nearest neighbors, decision tree, naive Bayes, and a neural network. Generalized linear mixed model analyses were used to assess the effects of case difficulty strata, ML algorithm, and the interaction between them in predicting accuracy. Results The results showed significant effects (P Conclusions This demonstration shows that using the IRT is a viable method for understanding the data that are provided to ML algorithms, independent of outcome measures, and highlights how well classifiers differentiate cases of varying difficulty. This method explains which features are indicative of healthy states and why. It enables end users to tailor the classifier that is appropriate to the difficulty level of the patient for personalized medicine.

Drug target interaction (DTI) prediction is a foundational task for in silico drug discovery, which is costly and time-consuming due to the need of experimental search over large drug compound space. Recent years have witnessed promising progress for deep learning in DTI predictions. However, the following challenges are still open: (1) the sole data-driven molecular representation learning approaches ignore the sub-structural nature of DTI, thus produce results that are less accurate and difficult to explain; (2) existing methods focus on limited labeled data while ignoring the value of massive unlabelled molecular data. We propose a Molecular Interaction Transformer (MolTrans) to address these limitations via: (1) knowledge inspired sub-structural pattern mining algorithm and interaction modeling module for more accurate and interpretable DTI prediction; (2) an augmented transformer encoder to better extract and capture the semantic relations among substructures extracted from massive unlabeled biomedical data. We evaluate MolTrans on real world data and show it improved DTI prediction performance compared to state-of-the-art baselines., Bioinformatics, 2020

Motivation The latest advances in cancer sequencing, and the availability of a wide range of methods to infer the evolutionary history of tumors, have made it important to evaluate, reconcile and cluster different tumor phylogenies. Recently, several notions of distance or similarities have been proposed in the literature, but none of them has emerged as the golden standard. Moreover, none of the known similarity measures is able to manage mutations occurring multiple times in the tree, a circumstance often occurring in real cases. Results To overcome these limitations, in this article, we propose MP3, the first similarity measure for tumor phylogenies able to effectively manage cases where multiple mutations can occur at the same time and mutations can occur multiple times. Moreover, a comparison of MP3 with other measures shows that it is able to classify correctly similar and dissimilar trees, both on simulated and on real data. Availability and implementation An open source implementation of MP3 is publicly available at https://github.com/AlgoLab/mp3treesim. Supplementary information Supplementary data are available at Bioinformatics online.