Machine learning-based prediction of transfusion.

BACKGROUND: The ability to predict transfusions arising during hospital admission might enable economized blood supply management and might furthermore increase patient safety by ensuring a sufficient stock of red blood cells (RBCs) for a specific patient. We therefore investigated the precision of four different machine learning-based prediction algorithms to predict transfusion, massive transfusion, and the number of transfusions in patients admitted to a hospital. STUDY DESIGN AND METHODS: This was a retrospective, observational study in three adult tertiary care hospitals in Western Australia between January 2008 and June 2017. Primary outcome measures for the classification tasks were the area under the curve for the receiver operating characteristics curve, the F1 score, and the average precision of the four machine learning algorithms used: neural networks (NNs), logistic regression (LR), random forests (RFs), and gradient boosting (GB) trees. RESULTS: Using our four predictive models, transfusion of at least 1 unit of RBCs could be predicted rather accurately (sensitivity for NN, LR, RF, and GB: 0.898, 0.894, 0.584, and 0.872, respectively; specificity: 0.958, 0.966, 0.964, 0.965). Using the four methods for prediction of massive transfusion was less successful (sensitivity for NN, LR, RF, and GB: 0.780, 0.721, 0.002, and 0.797, respectively; specificity: 0.994, 0.995, 0.993, 0.995). As a consequence, prediction of the total number of packed RBCs transfused was also rather inaccurate. CONCLUSION: This study demonstrates that the necessity for intrahospital transfusion can be forecasted reliably, however the amount of RBC units transfused during a hospital stay is more difficult to predict.

Furby: fuzzy force-directed bicluster visualization.

BACKGROUND: Cluster analysis is widely used to discover patterns in multi-dimensional data. Clustered heatmaps are the standard technique for visualizing one-way and two-way clustering results. In clustered heatmaps, rows and/or columns are reordered, resulting in a representation that shows the clusters as contiguous blocks. However, for biclustering results, where clusters can overlap, it is not possible to reorder the matrix in this way without duplicating rows and/or columns. RESULTS: We present Furby, an interactive visualization technique for analyzing biclustering results. Our contribution is twofold. First, the technique provides an overview of a biclustering result, showing the actual data that forms the individual clusters together with the information which rows and columns they share. Second, for fuzzy clustering results, the proposed technique additionally enables analysts to interactively set the thresholds that transform the fuzzy (soft) clustering into hard clusters that can then be investigated using heatmaps or bar charts. Changes in the membership value thresholds are immediately reflected in the visualization. We demonstrate the value of Furby by loading biclustering results applied to a multi-tissue dataset into the visualization. CONCLUSIONS: The proposed tool allows analysts to assess the overall quality of a biclustering result. Based on this high-level overview, analysts can then interactively explore the individual biclusters in detail. This novel way of handling fuzzy clustering results also supports analysts in finding the optimal thresholds that lead to the best clusters.

cn.MOPS: mixture of Poissons for discovering copy number variations in next-generation sequencing data with a low false discovery rate.

Quantitative analyses of next-generation sequencing (NGS) data, such as the detection of copy number variations (CNVs), remain challenging. Current methods detect CNVs as changes in the depth of coverage along chromosomes. Technological or genomic variations in the depth of coverage thus lead to a high false discovery rate (FDR), even upon correction for GC content. In the context of association studies between CNVs and disease, a high FDR means many false CNVs, thereby decreasing the discovery power of the study after correction for multiple testing. We propose 'Copy Number estimation by a Mixture Of PoissonS' (cn.MOPS), a data processing pipeline for CNV detection in NGS data. In contrast to previous approaches, cn.MOPS incorporates modeling of depths of coverage across samples at each genomic position. Therefore, cn.MOPS is not affected by read count variations along chromosomes. Using a Bayesian approach, cn.MOPS decomposes variations in the depth of coverage across samples into integer copy numbers and noise by means of its mixture components and Poisson distributions, respectively. The noise estimate allows for reducing the FDR by filtering out detections having high noise that are likely to be false detections. We compared cn.MOPS with the five most popular methods for CNV detection in NGS data using four benchmark datasets: (i) simulated data, (ii) NGS data from a male HapMap individual with implanted CNVs from the X chromosome, (iii) data from HapMap individuals with known CNVs, (iv) high coverage data from the 1000 Genomes Project. cn.MOPS outperformed its five competitors in terms of precision (1-FDR) and recall for both gains and losses in all benchmark data sets. The software cn.MOPS is publicly available as an R package at http://www.bioinf.jku.at/software/cnmops/ and at Bioconductor.

cn.FARMS: a latent variable model to detect copy number variations in microarray data with a low false discovery rate.

Cost-effective oligonucleotide genotyping arrays like the Affymetrix SNP 6.0 are still the predominant technique to measure DNA copy number variations (CNVs). However, CNV detection methods for microarrays overestimate both the number and the size of CNV regions and, consequently, suffer from a high false discovery rate (FDR). A high FDR means that many CNVs are wrongly detected and therefore not associated with a disease in a clinical study, though correction for multiple testing takes them into account and thereby decreases the study's discovery power. For controlling the FDR, we propose a probabilistic latent variable model, 'cn.FARMS', which is optimized by a Bayesian maximum a posteriori approach. cn.FARMS controls the FDR through the information gain of the posterior over the prior. The prior represents the null hypothesis of copy number 2 for all samples from which the posterior can only deviate by strong and consistent signals in the data. On HapMap data, cn.FARMS clearly outperformed the two most prevalent methods with respect to sensitivity and FDR. The software cn.FARMS is publicly available as a R package at http://www.bioinf.jku.at/software/cnfarms/cnfarms.html.

Machine Learning-Based Mortality Prediction of Patients at Risk During Hospital Admission.

OBJECTIVES: The ability to predict in-hospital mortality from data available at hospital admission would identify patients at risk and thereby assist hospital-wide patient safety initiatives. Our aim was to use modern machine learning tools to predict in-hospital mortality from standardized data sets available at hospital admission. METHODS: This was a retrospective, observational study in 3 adult tertiary care hospitals in Western Australia between January 2008 and June 2017. Primary outcome measures were the area under the curve for the receiver operating characteristics curve, the F1 score, and the average precision of the 4 machine learning algorithms used: logistic regression, neural networks, random forests, and gradient boosting trees. RESULTS: Using our 4 predictive models, in-hospital mortality could be predicted satisfactorily (areas under the curve for neural networks, logistic regression, random forests, and gradient boosting trees: 0.932, 0.936, 0.935, and 0.935, respectively), with moderate F1 scores: 0.378, 0.367, 0.380, and 0.380, respectively. Average precision values were 0.312, 0.321, 0.334, and 0.323, respectively. It remains unknown whether additional features might improve our models; however, this would result in additional efforts for data acquisition in daily clinical practice. CONCLUSIONS: This study demonstrates that using only a limited, standardized data set in-hospital mortality can be predicted satisfactorily at the time point of hospital admission. More parameters describing patient's health are likely needed to improve our model.

FABIA: factor analysis for bicluster acquisition.

MOTIVATION: Biclustering of transcriptomic data groups genes and samples simultaneously. It is emerging as a standard tool for extracting knowledge from gene expression measurements. We propose a novel generative approach for biclustering called 'FABIA: Factor Analysis for Bicluster Acquisition'. FABIA is based on a multiplicative model, which accounts for linear dependencies between gene expression and conditions, and also captures heavy-tailed distributions as observed in real-world transcriptomic data. The generative framework allows to utilize well-founded model selection methods and to apply Bayesian techniques. RESULTS: On 100 simulated datasets with known true, artificially implanted biclusters, FABIA clearly outperformed all 11 competitors. On these datasets, FABIA was able to separate spurious biclusters from true biclusters by ranking biclusters according to their information content. FABIA was tested on three microarray datasets with known subclusters, where it was two times the best and once the second best method among the compared biclustering approaches. AVAILABILITY: FABIA is available as an R package on Bioconductor (http://www.bioconductor.org). All datasets, results and software are available at http://www.bioinf.jku.at/software/fabia/fabia.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.