Remote monitoring and evaluation of pulmonary diseases via tele-medicine are important to disease diagnosis and management, but current telemedicine solutions have limited capability of objectively examining the airway's internal physiological conditions that are crucial to pulmonary disease evaluation. Existing solutions based on smartphone sensing are also limited to externally monitoring breath rates, respiratory events, or lung function. In this paper, we present PTEase, a new system design that addresses these limitations and uses commodity smartphones to examine the airway's internal physiological conditions. PTEase uses active acoustic sensing to measure the internal changes of lower airway caliber, and then leverages machine learning to analyze the sensory data for pulmonary disease evaluation. We implemented PTEase as a smartphone app, and verified its measurement error in lab-controlled settings as <10%. Clinical studies further showed that PTEase reaches 75% accuracy on disease prediction and 11%-15% errors in estimating lung function indices. Given that such accuracy is comparable with that in clinical practice using spirometry, PTEase can be reliably used as an assistive telemedicine tool for disease evaluation and monitoring.

Pulmonary diseases, such as asthma and Chronic Obstructive Pulmonary Disease (COPD), constitute a major public health challenge. The disease symptoms, including airway obstruction and inflammation, usually result in changes in airway mechanical properties, such as the caliber and impedance of the airway. To measure such airway properties for disease evaluation and diagnosis purposes, pulmonary function tests (PFT) has been widely adopted. However, most existing PFT systems require expensive and cumbersome hardware that are impossible to be used out of clinic. To allow out-clinic continuous pulmonary disease evaluation, in this paper we present AWARE, a new sensing and AI system that supports accurate and reliable PFT using commodity smartphones. AWARE uses a smartphone to transmit acoustic signals and reconstructs the profile of human airway based on the analysis of reflected acoustic waves captured from the smartphone's microphone. The subject's pulmonary condition is then evaluated by a multi-task learning model that integrates both the airway measurements and the subject's lung function records as the ground truth. Evaluations on 75 human subjects demonstrate that AWARE has the capability to achieve 80% accuracy on distinguishing between humans with healthy pulmonary function and with asthma symptoms.

MOTIVATION: Tissue-level omics data such as transcriptomics and epigenomics are an average across diverse cell types. To extract cell-type-specific (CTS) signals, dozens of cellular deconvolution methods have been proposed to infer cell-type fractions from tissue-level data. However, these methods produce vastly different results under various real data settings. Simulation-based benchmarking studies showed no universally best deconvolution approaches. There have been attempts of ensemble methods, but they only aggregate multiple single-cell references or reference-free deconvolution methods. RESULTS: To achieve a robust estimation of cellular fractions, we proposed EnsDeconv (Ensemble Deconvolution), which adopts CTS robust regression to synthesize the results from 11 single deconvolution methods, 10 reference datasets, 5 marker gene selection procedures, 5 data normalizations and 2 transformations. Unlike most benchmarking studies based on simulations, we compiled four large real datasets of 4937 tissue samples in total with measured cellular fractions and bulk gene expression from different tissues. Comprehensive evaluations demonstrated that EnsDeconv yields more stable, robust and accurate fractions than existing methods. We illustrated that EnsDeconv estimated cellular fractions enable various CTS downstream analyses such as differential fractions associated with clinical variables. We further extended EnsDeconv to analyze bulk DNA methylation data. AVAILABILITY AND IMPLEMENTATION: EnsDeconv is freely available as an R-package from https://github.com/randel/EnsDeconv. The RNA microarray data from the TRAUMA study are available and can be accessed in GEO (GSE36809). The demographic and clinical phenotypes can be shared on reasonable request to the corresponding authors. The RNA-seq data from the EVAPR study cannot be shared publicly due to the privacy of individuals that participated in the clinical research in compliance with the IRB approval at the University of Pittsburgh. The RNA microarray data from the FHS study are available from dbGaP (phs000007.v32.p13). The RNA-seq data from ROS study is downloaded from AD Knowledge Portal. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Allele-specific differences in molecular traits can be obtained from next-generation sequencing data and could potentially improve testing power, but such information is usually overlooked in association studies. Furthermore, the variation of molecular quantitative traits (e.g. gene expression) could result from the interaction effect of genotypes and phenotypes, but it is challenging to identify such interaction signals in complex disease studies in humans due to small genetic effect sizes and/or small sample sizes. RESULTS: We develop a novel statistical method, the combined haplotype interaction test (CHIT), which tests for association between molecular quantitative traits and phenotype-genotype interactions by modeling the total read counts and allele-specific reads in a target region. CHIT can be used as a supplementary analysis to the regular linear interaction regression. In our simulations, CHIT obtains non-inflated type I error rates, and it has higher power than a standard interaction quantitative trait locus approach based on linear regression models. Finally, we illustrate CHIT by testing associations between gene expression obtained by RNA-seq and the interaction of SNPs and atopy status from a study of childhood asthma in Puerto Ricans, and results demonstrate that CHIT could be more powerful than a standard linear interaction expression quantitative trait loci approach. AVAILABILITY AND IMPLEMENTATION: The CHIT algorithm has been implemented in Python. The source code and documentation are available and can be downloaded from https://github.com/QiYanPitt/CHIT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Respiratory diseases have been a significant public health challenge. Efficient disease evaluation and monitoring call for daily spirometry tests, as an effective way of pulmonary function testing, out of clinic. This requirement, however, is hard to be satisfied due to the large size and high costs of current spirometry equipments. In this paper, we present SpiroSonic, a new system design that uses commodity smartphones to support complete, accurate yet reliable spirometry tests in regular home settings with various environmental and human factors. SpiroSonic measures the humans' chest wall motion via acoustic sensing and interprets such motion into lung function indices, based on the clinically validated correlation between them. We implemented SpiroSonic as a smartphone app, and verified SpiroSonic's monitoring error over healthy humans as <3%. Clinical studies further show that SpiroSonic reaches 5%-10% monitoring error among 83 pediatric patients. Given that the error of in-clinic spirometry is usually around 5%, SpiroSonic can be reliably used for disease tracking and evaluation out of clinic.

Device-free acoustic motion tracking allows a commodity mobile device to precisely track the human user's motion, without applying any extra hardware tracker on the human body. Most of current device-free acoustic motion tracking systems, however, are limited to tracking the motion of small parts of the human body with negligible sizes, such as human fingers. Their accuracy of motion tracking will significantly degrade when being applied to targets with large sizes, such as humans' hands, arms or body trunk. We envision the key reason to such degradation as the target size's significant impact on the pattern of the reflected acoustic signal, and develop analytical modeling of such reflected acoustic signal from large targets. Based on such modeling, we present a new system called Acoustic Tracking over targets with LArge Sizes (ATLAS), which ensures precise motion tracking over large targets by correctly interpreting the reflected acoustic signal and extracting the phase from the signal. Experiment results over commodity Android smartphones show that ATLAS can reduce the error of motion tracking by more than 75%, when being applied to targets with heterogeneous sizes in practice.