Feature selection, aiming to identify a subset of features among a possibly large set of features that are relevant for predicting a response, is an important preprocessing step in machine learning. In gene expression studies this is not a trivial task for several reasons, including potential temporal character of data. However, most feature selection approaches developed for microarray data cannot handle multivariate temporal data without previous data flattening, which results in loss of temporal information. We propose a temporal minimum redundancy - maximum relevance (TMRMR) feature selection approach, which is able to handle multivariate temporal data without previous data flattening. In the proposed approach we compute relevance of a gene by averaging F-statistic values calculated across individual time steps, and we compute redundancy between genes by using a dynamical time warping approach. The proposed method is evaluated on three temporal gene expression datasets from human viral challenge studies. Obtained results show that the proposed method outperforms alternatives widely used in gene expression studies. In particular, the proposed method achieved improvement in accuracy in 34 out of 54 experiments, while the other methods outperformed it in no more than 4 experiments. We developed a filter-based feature selection method for temporal gene expression data based on maximum relevance and minimum redundancy criteria. The proposed method incorporates temporal information by combining relevance, which is calculated as an average F-statistic value across different time steps, with redundancy, which is calculated by employing dynamical time warping approach. As evident in our experiments, incorporating the temporal information into the feature selection process leads to selection of more discriminative features.

Background: Machine learning models have been adapted in biomedical research and practice for knowledge discovery and decision support. While mainstream biomedical informatics research focuses on developing more accurate models, the importance of data preprocessing draws less attention. We propose the Generalized Logistic (GL) algorithm that scales data uniformly to an appropriate interval by learning a generalized logistic function to fit the empirical cumulative distribution function of the data. The GL algorithm is simple yet effective; it is intrinsically robust to outliers, so it is particularly suitable for diagnostic/classification models in clinical/medical applications where the number of samples is usually small; it scales the data in a nonlinear fashion, which leads to potential improvement in accuracy. Results: To evaluate the effectiveness of the proposed algorithm, we conducted experiments on 16 binary classification tasks with different variable types and cover a wide range of applications. The resultant performance in terms of area under the receiver operation characteristic curve (AUROC) and percentage of correct classification showed that models learned using data scaled by the GL algorithm outperform the ones using data scaled by the Min-max and the Z-score algorithm, which are the most commonly used data scaling algorithms. Conclusion: The proposed GL algorithm is simple and effective. It is robust to outliers, so no additional denoising or outlier detection step is needed in data preprocessing. Empirical results also show models learned from data scaled by the GL algorithm have higher accuracy compared to the commonly used data scaling algorithms.

Keeping track of blood glucose levels non-invasively is now possible due to diverse breakthroughs in wearable sensors technology coupled with advanced biomedical signal processing. However, each user might have different requirements and priorities when it comes to selecting a self-monitoring solution. After extensive research and careful selection, we have presented a comprehensive survey on noninvasive/pain-free blood glucose monitoring methods from the recent five years (2012-2016). Several techniques, from bioinformatics, computer science, chemical engineering, microwave technology, etc., are discussed in order to cover a wide variety of solutions available for different scales and preferences. We categorize the noninvasive techniques into nonsample- and sample-based techniques, which we further grouped into optical, nonoptical, intermittent, and continuous. The devices manufactured or being manufactured for noninvasive monitoring are also compared in this paper. These techniques are then analyzed based on certain constraints, which include time efficiency, comfort, cost, portability, power consumption, etc., a user might experience. Recalibration, time, and power efficiency are the biggest challenges that require further research in order to satisfy a large number of users. In order to solve these challenges, artificial intelligence (AI) has been employed by many researchers. AI-based estimation and decision models hold the future of noninvasive glucose monitoring in terms of accuracy, cost effectiveness, portability, efficiency, etc. The significance of this paper is twofold: first, to bridge the gap between IT and medical field; and second, to bridge the gap between end users and the solutions (hardware and software).

Early classification of time series is beneficial for biomedical informatics problems such including, but not limited to, disease change detection. Early classification can be of tremendous help by identifying the onset of a disease before it has time to fully take hold. In addition, extracting patterns from the original time series helps domain experts to gain insights into the classification results. This problem has been studied recently using time series segments called shapelets. In this paper, we present a method, which we call Multivariate Shapelets Detection (MSD), that allows for early and patient-specific classification of multivariate time series. The method extracts time series patterns, called multivariate shapelets, from all dimensions of the time series that distinctly manifest the target class locally. The time series were classified by searching for the earliest closest patterns.

Background: Infant birth weight is a complex quantitative trait associated with both neonatal and long-term health outcomes. Numerous studies have been published in which candidate genes (IGF1, IGF2, IGF2R, IGFbinding proteins,PHLDA2andPLAGL1) have been associated with birth weight, but these studies are difficult to reproduce in man and large cohort studies are needed due to the large inter individual variance in transcription levels. Also, very little of the trait variance is explained. We decided to identify additional candidates without regard for what is known about the genes. We hypothesize that DNA methylation differences between individuals can serve as markers of gene "expression potential" at growth related genes throughout development and that these differences may correlate with birth weight better than single time point measures of gene expression.Methods: We performed DNA methylation and transcript profiling on cord blood and placenta from newborns. We then used novel computational approaches to identify genes correlated with birth weight.Results: We identified 23 genes whose methylation levels explain 70-87% of the variance in birth weight. Six of these (ANGPT4, APOE, CDK2, GRB10, OSBPL5andREG1B) are associated with growth phenotypes in human or mouse models. Gene expression profiling explained a much smaller fraction of variance in birth weight than did DNA methylation. We further show that two genes, the transcriptional repressorMSX1and the growth factor receptor adaptor proteinGRB10, are correlated with transcriptional control of at least seven genes reported to be involved in fetal or placental growth, suggesting that we have identified important networks in growth control.GRB10methylation is also correlated with genes involved in reactive oxygen species signaling, stress signaling and oxygen sensing and more recent data implicateGRB10in insulin signaling.Conclusions: Single time point measurements of gene expression may reflect many factors unrelated to birth weight, while inter-individual differences in DNA methylation may represent a "molecular fossil record" of differences in birth weight-related gene expression. Finding these "unexpected" pathways may tell us something about the long-term association between low birth weight and adult disease, as well as which genes may be susceptible to environmental effects. These findings increase our understanding of the molecular mechanisms involved in human development and disease progression.

Objective: We sought to predict if patients with type 2 diabetes mellitus (DM2) would develop 10 selected complications. Accurate prediction of complications could help with more targeted measures that would prevent or slow down their development.Materials and Methods: Experiments were conducted on the Healthcare Cost and Utilization Project State Inpatient Databases of California for the period of 2003 to 2011. Recurrent neural network (RNN) long short-term memory (LSTM) and RNN gated recurrent unit (GRU) deep learning methods were designed and compared with random forest and multilayer perceptron traditional models. Prediction accuracy of selected complications were compared on 3 settings corresponding to minimum number of hospitalizations between diabetes diagnosis and the diagnosis of complications.Results: The diagnosis domain was used for experiments. The best results were achieved with RNN GRU model, followed by RNN LSTM model. The prediction accuracy achieved with RNN GRU model was between 73% (myocardial infarction) and 83% (chronic ischemic heart disease), while accuracy of traditional models was between 66% – 76%.Discussion: The number of hospitalizations was an important factor for the prediction accuracy. Experiments with 4 hospitalizations achieved significantly better accuracy than with 2 hospitalizations. To achieve improved accuracy deep learning models required training on at least 1000 patients and accuracy significantly dropped if training datasets contained 500 patients. The prediction accuracy of complications decreases over time period. Considering individual complications, the best accuracy was achieved on depressive disorder and chronic ischemic heart disease.Conclusions: The RNN GRU model was the best choice for electronic medical record type of data, based on the achieved results.