MotivationA central task of bioinformatics is to develop sensitive and specific means of providing medical prognoses from biomarker patterns. Common methods to predict phenotypes in RNA-Seq datasets utilize machine learning algorithms trained via gene expression. Isoforms, however, generated from alternative splicing, may provide a novel and complementary set of transcripts for phenotype prediction. In contrast to gene expression, the number of isoforms increases significantly due to numerous alternative splicing patterns, resulting in a prioritization problem for many machine learning algorithms. This study identifies the empirically optimal methods of transcript quantification, feature engineering and filtering steps using phenotype prediction accuracy as a metric. At the same time, the complementary nature of gene and isoform data is analyzed and the feasibility of identifying isoforms as biomarker candidates is examined.ResultsIsoform features are complementary to gene features, providing non-redundant information and enhanced predictive power when prioritized and filtered. A univariate filtering algorithm, which selects up to the N highest ranking features for phenotype prediction is described and evaluated in this study. An empirical comparison of pipelines for isoform quantification is reported by performing cross-validation prediction tests with datasets from human non-small cell lung cancer (NSCLC) patients, human patients with chronic obstructive pulmonary disease (COPD) and amyotrophic lateral sclerosis (ALS) transgenic mice, each including samples of diseased and non-diseased phenotypes.Availability and Implementation https://github.com/clabuzze/Phenotype-Prediction-Pipeline.git Contact clabuzze@iastate.edu, antoniom@bc.edu, watsondk@musc.edu, andersonpe2@cofc.edu

Global surface water classification layers, such as the European Joint Research Centre’s (JRC) Monthly Water History dataset, provide a starting point for accurate and large scale analyses of trends in waterbody extents. On the local scale, there is an opportunity to increase the accuracy and temporal frequency of these surface water maps by using locally trained classifiers and gap-filling missing values via imputation in all available satellite images. We developed the Surface Water IMputation (SWIM) classification framework using R and the Google Earth Engine computing platform to improve water classification compared to the JRC study. The novel contributions of the SWIM classification framework include (1) a cluster-based algorithm to improve classification sensitivity to a variety of surface water conditions and produce approximately unbiased estimation of surface water area, (2) a method to gap-fill every available Landsat image for a region of interest to generate submonthly classifications at the highest possible temporal frequency, (3) an outlier detection method for identifying images that contain classification errors due to failures in cloud masking. Validation and several case studies demonstrate the SWIM classification framework outperforms the JRC dataset in spatiotemporal analyses of small waterbody dynamics with previously unattainable sensitivity and temporal frequency. Most importantly, this study shows that reliable surface water classifications can be obtained for all pixels in every available Landsat image, even those containing cloud cover, after performing gap-fill imputation. By using this technique, the SWIM framework supports monitoring water extent on a submonthly basis, which is especially applicable to assessing the impact of short-term flood and drought events. Additionally, our results contribute to addressing the challenges of training machine learning classifiers with biased ground truth data and identifying images that contain regions of anomalous classification errors.

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