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Countries globally reacted to the COVID-19 pandemic by imposing lockdowns, and as a consequence, higher education institutions were forced to rapidly transition into distance learning. Here, technology played a paramount role as the enabler of remote learning and shaping teaching practices. The aim of this study is to understand the broad trends in higher education during the early lockdown transitions and the role of technology in this process through a literature review approach. After searching for literature and applying inclusion and exclusion criteria, 61 relevant publications were discovered, which were sorted into three clusters using co-word analysis: (1) teaching and learning; (2) policy and managerial issues; and (3) students' psychological well-being. Each theme was further divided into subthemes based on a thematic clustering approach. Based on this review, implications on learning technology design during the time of a pandemic were derived. First, due to the lack of social contacts resulting from isolation measures, emphasis is needed on interstudent interaction. Second, mobile distance learning technologies and teaching methods could be designed to enable students to move or exercise while learning. Third, diverse pedagogical approaches should be looked into to bring variety into students' lives. publishedVersion

We present a method for training neural networks with synthetic electrocardiograms that mimic signals produced by a wearable single lead electrocardiogram monitor. We use domain randomization where the synthetic signal properties such as the waveform shape, RR-intervals and noise are varied for every training example. Models trained with synthetic data are compared to their counterparts trained with real data. Detection of r-waves in electrocardiograms recorded during different physical activities and in atrial fibrillation is used to compare the models. By allowing the randomization to increase beyond what is typically observed in the real-world data the performance is on par or superseding the performance of networks trained with real data. Experiments show robust performance with different seeds and training examples on different test sets without any test set specific tuning. The method makes possible to train neural networks using practically free-to-collect data with accurate labels without the need for manual annotations and it opens up the possibility of extending the use of synthetic data on cardiac disease classification when disease specific a priori information is used in the electrocardiogram generation. Additionally the distribution of data can be controlled eliminating class imbalances that are typically observed in health related data and additionally the generated data is inherently private.

We study the combinatorics of cross-validation based AUC estimation under the null hypothesis that the binary class labels are exchangeable, that is, the data are randomly assigned into two classes given a fixed class proportion. In particular, we study how the estimators based on leave-pair-out cross-validation (LPOCV), in which every possible pair of data with different class labels is held out from the training set at a time, behave under the null without any prior assumptions of the learning algorithm or the data. It is shown that the maximal number of different fixed proportion label assignments on a sample of data, for which a learning algorithm can achieve zero LPOCV error, is the maximal size of a constant weight error correcting code, whose length is the sample size, weight is the number of data labeled with one, and the Hamming distance between code words is four. We then introduce the concept of a light constant weight code and show similar results for nonzero LPOCV errors. We also prove both upper and lower bounds on the maximal sizes of the light constant weight codes that are similar to the classical results for contant weight codes. These results pave the way towards the design of new LPOCV based statistical tests for the learning algorithms ability of distinguishing two classes from each other that are analogous to the classical Wilcoxon-Mann-Whitney U test for fixed functions. Behavior of some representative examples of learning algorithms and data are simulated in an experimental case study.

Receiver operating characteristic analysis is widely used for evaluating diagnostic systems. Recent studies have shown that estimating an area under receiver operating characteristic curve with standard cross-validation methods suffers from a large bias. The leave-pair-out cross-validation has been shown to correct this bias. However, while leave-pair-out produces an almost unbiased estimate of area under receiver operating characteristic curve, it does not provide a ranking of the data needed for plotting and analyzing the receiver operating characteristic curve. In this study, we propose a new method called tournament leave-pair-out cross-validation. This method extends leave-pair-out by creating a tournament from pair comparisons to produce a ranking for the data. Tournament leave-pair-out preserves the advantage of leave-pair-out for estimating area under receiver operating characteristic curve, while it also allows performing receiver operating characteristic analyses. We have shown using both synthetic and real-world data that tournament leave-pair-out is as reliable as leave-pair-out for area under receiver operating characteristic curve estimation and confirmed the bias in leave-one-out cross-validation on low-dimensional data. As a case study on receiver operating characteristic analysis, we also evaluate how reliably sensitivity and specificity can be estimated from tournament leave-pair-out receiver operating characteristic curves.

Introduction Predictive survival modeling offers systematic tools for clinical decision-making and individualized tailoring of treatment strategies to improve patient outcomes while reducing overall healthcare costs. In 2015, a number of machine learning and statistical models were benchmarked in the DREAM 9.5 Prostate Cancer Challenge, based on open clinical trial data for metastatic castration resistant prostate cancer (mCRPC). However, applying these models into clinical practice poses a practical challenge due to the inclusion of a large number of model variables, some of which are not routinely monitored or are expensive to measure. Objectives To develop cost-specified variable selection algorithms for constructing cost-effective prognostic models of overall survival that still preserve sufficient model performance for clinical decision making. Methods Penalized Cox regression models were used for the survival prediction. For the variable selection, we implemented two algorithms: (i) LASSO regularization approach; and (ii) a greedy cost-specified variable selection algorithm. The models were compared in three cohorts of mCRPC patients from randomized clinical trials (RCT), as well as in a real-world cohort (RWC) of advanced prostate cancer patients treated at the Turku University Hospital. Hospital laboratory expenses were utilized as a reference for computing the costs of introducing new variables into the models. Results Compared to measuring the full set of clinical variables, economic costs could be reduced by half without a significant loss of model performance. The greedy algorithm outperformed the LASSO-based variable selection with the lowest tested budgets. The overall top performance was higher with the LASSO algorithm. Conclusion The cost-specified variable selection offers significant budget optimization capability for the real-world survival prediction without compromising the predictive power of the model.

Supplemental material for Tournament leave-pair-out cross-validation for receiver operating characteristic analysis by Ileana Montoya Perez, Antti Airola, Peter J Boström, Ivan Jambor and Tapio Pahikkala in Statistical Methods in Medical Research

Receiver operating characteristic (ROC) analysis is widely used for evaluating diagnostic systems. Recent studies have shown that estimating an area under ROC curve (AUC) with standard cross-validation methods suffers from a large bias. The leave-pair-out (LPO) cross-validation has been shown to correct this bias. However, while LPO produces an almost unbiased estimate of AUC, it does not provide a ranking of the data needed for plotting and analyzing the ROC curve. In this study, we propose a new method called tournament leave-pair-out (TLPO) cross-validation. This method extends LPO by creating a tournament from pair comparisons to produce a ranking for the data. TLPO preserves the advantage of LPO for estimating AUC, while it also allows performing ROC analysis. We have shown using both synthetic and real world data that TLPO is as reliable as LPO for AUC estimation and confirmed the bias in leave-one-out cross-validation on low-dimensional data., Comment: 13 pages, 8 figures

We report the results of a DREAM challenge designed to predict relative genetic essentialities based on a novel dataset testing 98,000 shRNAs against 149 molecularly characterized cancer cell lines. We analyzed the results of over 3,000 submissions over a period of 4months. We found that algorithms combining essentiality data across multiple genes demonstrated increased accuracy; gene expression was the most informative molecular data type; the identity of the gene being predicted was far more important than the modeling strategy; well-predicted genes and selected molecular features showed enrichment in functional categories; and frequently selected expression features correlated with survival in primary tumors. This study establishes benchmarks for geneessentiality prediction, presents a community resource for future comparison with this benchmark, and provides insights into factors influencing the ability to predict gene essentiality from functional genetic screens. This study also demonstrates the value of releasing pre-publication data publicly to engage the community in an open research collaboration.

Due to relatively high costs and labor required for experimental profiling of the full target space of chemical compounds, various machine learning models have been proposed as cost-effective means to advance this process in terms of predicting the most potent compound-target interactions for subsequent verification. However, most of the model predictions lack direct experimental validation in the laboratory, making their practical benefits for drug discovery or repurposing applications largely unknown. Here, we therefore introduce and carefully test a systematic computational-experimental framework for the prediction and pre-clinical verification of drug-target interactions using a well-established kernel-based regression algorithm as the prediction model. To evaluate its performance, we first predicted unmeasured binding affinities in a large-scale kinase inhibitor profiling study, and then experimentally tested 100 compound-kinase pairs. The relatively high correlation of 0.77 (p < 0.0001) between the predicted and measured bioactivities supports the potential of the model for filling the experimental gaps in existing compound-target interaction maps. Further, we subjected the model to a more challenging task of predicting target interactions for such a new candidate drug compound that lacks prior binding profile information. As a specific case study, we used tivozanib, an investigational VEGF receptor inhibitor with currently unknown off-target profile. Among 7 kinases with high predicted affinity, we experimentally validated 4 new off-targets of tivozanib, namely the Src-family kinases FRK and FYN A, the non-receptor tyrosine kinase ABL1, and the serine/threonine kinase SLK. Our sub-sequent experimental validation protocol effectively avoids any possible information leakage between the training and validation data, and therefore enables rigorous model validation for practical applications. These results demonstrate that the kernel-based modeling approach offers practical benefits for probing novel insights into the mode of action of investigational compounds, and for the identification of new target selectivities for drug repurposing applications.

Pairwise learning or dyadic prediction concerns the prediction of properties for pairs of objects. It can be seen as an umbrella covering various machine learning problems such as matrix completion, collaborative filtering, multi-task learning, transfer learning, network prediction and zero-shot learning. In this work we analyze kernel-based methods for pairwise learning, with a particular focus on a recently-suggested two-step method. We show that this method offers an appealing alternative for commonly-applied Kronecker-based methods that model dyads by means of pairwise feature representations and pairwise kernels. In a series of theoretical results, we establish correspondences between the two types of methods in terms of linear algebra and spectral filtering, and we analyze their statistical consistency. In addition, the two-step method allows us to establish novel algorithmic shortcuts for efficient training and validation on very large datasets. Putting those properties together, we believe that this simple, yet powerful method can become a standard tool for many problems. Extensive experimental results for a range of practical settings are reported.

We consider the problem of learning regression functions from pairwise data when there exists prior knowledge that the relation to be learned is symmetric or anti-symmetric. Such prior knowledge is commonly enforced by symmetrizing or anti-symmetrizing pairwise kernel functions. Through spectral analysis, we show that these transformations reduce the kernel's effective dimension. Further, we provide an analysis of the approximation properties of the resulting kernels, and bound the regularization bias of the kernels in terms of the corresponding bias of the original kernel.

Dyadic prediction methods operate on pairs of objects (dyads), aiming to infer labels for out-of-sample dyads. We consider the full and almost full cold start problem in dyadic prediction, a setting that occurs when both objects in an out-of-sample dyad have not been observed during training, or if one of them has been observed, but very few times. A popular approach for addressing this problem is to train a model that makes predictions based on a pairwise feature representation of the dyads, or, in case of kernel methods, based on a tensor product pairwise kernel. As an alternative to such a kernel approach, we introduce a novel two-step learning algorithm that borrows ideas from the fields of pairwise learning and spectral filtering. We show theoretically that the two-step method is very closely related to the tensor product kernel approach, and experimentally that it yields a slightly better predictive performance. Moreover, unlike existing tensor product kernel methods, the two-step method allows closed-form solutions for training and parameter selection via cross-validation estimates both in the full and almost full cold start settings, making the approach much more efficient and straightforward to implement.

We propose a novel algorithm for greedy forward feature selection for regularized least-squares (RLS) regression and classification, also known as the least-squares support vector machine or ridge regression. The algorithm, which we call greedy RLS, starts from the empty feature set, and on each iteration adds the feature whose addition provides the best leave-one-out cross-validation performance. Our method is considerably faster than the previously proposed ones, since its time complexity is linear in the number of training examples, the number of features in the original data set, and the desired size of the set of selected features. Therefore, as a side effect we obtain a new training algorithm for learning sparse linear RLS predictors which can be used for large scale learning. This speed is possible due to matrix calculus based short-cuts for leave-one-out and feature addition. We experimentally demonstrate the scalability of our algorithm and its ability to find good quality feature sets., 17 pages, 15 figures

Reliable estimation of the classification performance of learned predictive models is difficult, when working in the small sample setting. When dealing with biological data it is often the case that separate test data cannot be afforded. Cross-validation is in this case a typical strategy for estimating the performance. Recent results, further supported by experimental evidence presented in this article, show that many standard approaches to cross-validation suffer from extensive bias or variance when the area under ROC curve (AUC) is used as performance measure. We advocate the use of leave-pair-out cross-validation (LPOCV) for performance estimation, as it avoids many of these problems. A method previously proposed by us can be used to efficiently calculate this estimate for regularized least-squares (RLS) based learners.