Elastic analysis of irregularly or sparsely sampled curves.

We provide statistical analysis methods for samples of curves in two or more dimensions, where the image, but not the parameterization of the curves, is of interest and suitable alignment/registration is thus necessary. Examples are handwritten letters, movement paths, or object outlines. We focus in particular on the computation of (smooth) means and distances, allowing, for example, classification or clustering. Existing parameterization invariant analysis methods based on the elastic distance of the curves modulo parameterization, using the square-root-velocity framework, have limitations in common realistic settings where curves are irregularly and potentially sparsely observed. We propose using spline curves to model smooth or polygonal (Fréchet) means of open or closed curves with respect to the elastic distance and show identifiability of the spline model modulo parameterization. We further provide methods and algorithms to approximate the elastic distance for irregularly or sparsely observed curves, via interpreting them as polygons. We illustrate the usefulness of our methods on two datasets. The first application classifies irregularly sampled spirals drawn by Parkinson's patients and healthy controls, based on the elastic distance to a mean spiral curve computed using our approach. The second application clusters sparsely sampled GPS tracks based on the elastic distance and computes smooth cluster means to find new paths on the Tempelhof field in Berlin. All methods are implemented in the R-package "elasdics" and evaluated in simulations.

Pedestrian exposure to black carbon and PM2.5 emissions in urban hot spots: new findings using mobile measurement techniques and flexible Bayesian regression models.

BACKGROUND: Data from extensive mobile measurements (MM) of air pollutants provide spatially resolved information on pedestrians' exposure to particulate matter (black carbon (BC) and PM2.5 mass concentrations). OBJECTIVE: We present a distributional regression model in a Bayesian framework that estimates the effects of spatiotemporal factors on the pollutant concentrations influencing pedestrian exposure. METHODS: We modeled the mean and variance of the pollutant concentrations obtained from MM in two cities and extended commonly used lognormal models with a lognormal-normal convolution (logNNC) extension for BC to account for instrument measurement error. RESULTS: The logNNC extension significantly improved the BC model. From these model results, we found local sources and, hence, local mitigation efforts to improve air quality, have more impact on the ambient levels of BC mass concentrations than on the regulated PM2.5. SIGNIFICANCE: Firstly, this model (logNNC in bamlss package available in R) could be used for the statistical analysis of MM data from various study areas and pollutants with the potential for predicting pollutant concentrations in urban areas. Secondly, with respect to pedestrian exposure, it is crucial for BC mass concentration to be monitored and regulated in areas dominated by traffic-related air pollution.

Classifying neck pain status using scalar and functional biomechanical variables - development of a method using functional data boosting.

BACKGROUND: Individuals with neck pain have different movement and muscular activation (collectively termed as biomechanical variables) patterns compared to healthy individuals. Incorporating biomechanical variables as covariates into prognostic models is challenging due to the high dimensionality of the data. RESEARCH QUESTION: What is the classification performance of neck pain status of a statistical model which uses both scalar and functional biomechanical covariates? METHODS: Motion capture with electromyography assessment on the sternocleidomastoid, splenius cervicis, erector spinae, was performed on 21 healthy and 26 individuals with neck pain during walking over three gait conditions (rectilinear, curvilinear clockwise (CW) and counterclockwise (CCW)). After removing highly collinear variables, 94 covariates across the three conditions were used to classify neck pain status using functional data boosting (FDboost). RESULTS: Two functional covariates trunk lateral flexion angle during CCW gait, and trunk flexion angle during CW gait; and a scalar covariate, hip jerk index during CCW gait were selected. The model achieved an estimated AUC of 80.8 %. For hip jerk index, an increase in hip jerk index by one unit increased the log odds of being in the neck pain group by 0.37. A 1° increase in trunk lateral flexion angle throughout gait alone reduced the probability of being in the neck pain group from 0.5 to 0.15. A 1° increase in trunk flexion angle throughout gait alone increased the probability of being in the neck pain group from 0.5 to 0.9. SIGNIFICANCE: Interpreting the physiological significance of the extracted covariates, with other biomechanical variables, suggests that individuals with neck pain performed curvilinear walking using a stiffer strategy, compared to controls; and this increased the risk of being in the neck pain group. FDboost can produce clinically interpretable models with complex high dimensional data and could be used in future prognostic modelling studies in neck pain research.

QUANTIFYING ALTERNATIVE SPLICING FROM PAIRED-END RNA-SEQUENCING DATA.

RNA-sequencing has revolutionized biomedical research and, in particular, our ability to study gene alternative splicing. The problem has important implications for human health, as alternative splicing may be involved in malfunctions at the cellular level and multiple diseases. However, the high-dimensional nature of the data and the existence of experimental biases pose serious data analysis challenges. We find that the standard data summaries used to study alternative splicing are severely limited, as they ignore a substantial amount of valuable information. Current data analysis methods are based on such summaries and are hence sub-optimal. Further, they have limited flexibility in accounting for technical biases. We propose novel data summaries and a Bayesian modeling framework that overcome these limitations and determine biases in a non-parametric, highly flexible manner. These summaries adapt naturally to the rapid improvements in sequencing technology. We provide efficient point estimates and uncertainty assessments. The approach allows to study alternative splicing patterns for individual samples and can also be the basis for downstream analyses. We found a several fold improvement in estimation mean square error compared popular approaches in simulations, and substantially higher consistency between replicates in experimental data. Our findings indicate the need for adjusting the routine summarization and analysis of alternative splicing RNA-seq studies. We provide a software implementation in the R package casper.