Cancers are composed of genetically distinct subpopulations of malignant cells. DNA-sequencing data can be used to determine the somatic point mutations specific to each population and build clone trees describing the evolutionary relationships between them. These clone trees can reveal critical points in disease development and inform treatment. Pairtree is a new method that constructs more accurate and detailed clone trees than previously possible using variant allele frequency data from one or more bulk cancer samples. It does so by first building a Pairs Tensor that captures the evolutionary relationships between pairs of subpopulations, and then it uses these relations to constrain clone trees and infer violations of the infinite sites assumption. Pairtree can accurately build clone trees using up to 100 samples per cancer that contain 30 or more subclonal populations. On 14 B-progenitor acute lymphoblastic leukemias, Pairtree replicates or improves upon expert-derived clone tree reconstructions. Significance: Clone trees illustrate the evolutionary history of a cancer and can provide insights into how the disease changed through time (e.g., between diagnosis and relapse). Pairtree uses DNA-sequencing data from many samples of the same cancer to build more detailed and accurate clone trees than previously possible. See related commentary by Miller.

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Wearable biosensors can be used to monitor opioid use, a problem of dire societal consequence given the current opioid epidemic in the US. Such surveillance can prompt interventions that promote behavioral change. Prior work has focused on the use of wearable biosensor data to detect opioid use. In this work, we present a method that uses machine learning to identify opioid withdrawal using data collected with a wearable biosensor. Our method involves developing a set of machine-learning classifiers, and then evaluating those classifiers using unseen test data. An analysis of the best performing model (based on the Random Forest algorithm) produced a receiver operating characteristic (ROC) area under the curve (AUC) of 0.9997 using completely unseen test data. Further, the model is able to detect withdrawal with just one minute of biosensor data. These results show the viability of using machine learning for opioid withdrawal detection. To our knowledge, the proposed method for identifying opioid withdrawal in OUD patients is the first of its kind.

Supplementary Data from Reconstructing Complex Cancer Evolutionary Histories from Multiple Bulk DNA Samples Using Pairtree