Variable selection for BART: An application to gene regulation

We consider the task of discovering gene regulatory networks, which are defined as sets of genes and the corresponding transcription factors which regulate their expression levels. This can be viewed as a variable selection problem, potentially with high dimensionality. Variable selection is especially challenging in high-dimensional settings, where it is difficult to detect subtle individual effects and interactions between predictors. Bayesian Additive Regression Trees [BART, Ann. Appl. Stat. 4 (2010) 266-298] provides a novel nonparametric alternative to parametric regression approaches, such as the lasso or stepwise regression, especially when the number of relevant predictors is sparse relative to the total number of available predictors and the fundamental relationships are nonlinear. We develop a principled permutation-based inferential approach for determining when the effect of a selected predictor is likely to be real. Going further, we adapt the BART procedure to incorporate informed prior information about variable importance. We present simulations demonstrating that our method compares favorably to existing parametric and nonparametric procedures in a variety of data settings. To demonstrate the potential of our approach in a biological context, we apply it to the task of inferring the gene regulatory network in yeast (Saccharomyces cerevisiae). We find that our BART-based procedure is best able to recover the subset of covariates with the largest signal compared to other variable selection methods. The methods developed in this work are readily available in the R package bartMachine.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS755 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Neuro-Musculoskeletal Mapping for Man-Machine Interfacing.

We propose a myoelectric control method based on neural data regression and musculoskeletal modeling. This paradigm uses the timings of motor neuron discharges decoded by high-density surface electromyogram (HD-EMG) decomposition to estimate muscle excitations. The muscle excitations are then mapped into the kinematics of the wrist joint using forward dynamics. The offline tracking performance of the proposed method was superior to that of state-of-the-art myoelectric regression methods based on artificial neural networks in two amputees and in four out of six intact-bodied subjects. In addition to joint kinematics, the proposed data-driven model-based approach also estimated several biomechanical variables in a full feed-forward manner that could potentially be useful in supporting the rehabilitation and training process. These results indicate that using a full forward dynamics musculoskeletal model directly driven by motor neuron activity is a promising approach in rehabilitation and prosthetics to model the series of transformations from muscle excitation to resulting joint function

Motor unit characteristics after targeted muscle reinnervation

Targeted muscle reinnervation (TMR) is a surgical procedure used to redirect nerves originally controlling muscles of the amputated limb into remaining muscles above the amputation, to treat phantom limb pain and facilitate prosthetic control. While this procedure effectively establishes robust prosthetic control, there is little knowledge on the behavior and characteristics of the reinnervated motor units. In this study we compared the m. pectoralis of five TMR patients to nine able-bodied controls with respect to motor unit action potential (MUAP) characteristics. We recorded and decomposed high-density surface EMG signals into individual spike trains of motor unit action potentials. In the TMR patients the MUAP surface area normalized to the electrode grid surface (0.25 ± 0.17 and 0.81 ± 0.46, p < 0.001) and the MUAP duration (10.92 ± 3.89 ms and 14.03 ± 3.91 ms, p < 0.01) were smaller for the TMR group than for the controls. The mean MUAP amplitude (0.19 ± 0.11 mV and 0.14 ± 0.06 mV, p = 0.07) was not significantly different between the two groups. Finally, we observed that MUAP surface representation in TMR generally overlapped, and the surface occupied by motor units corresponding to only one motor task was on average smaller than 12% of the electrode surface. These results suggest that smaller MUAP surface areas in TMR patients do not necessarily facilitate prosthetic control due to a high degree of overlap between these areas, and a neural information—based control could lead to improved performance. Based on the results we also infer that the size of the motor units after reinnervation is influenced by the size of the innervating motor neuron

Pattern Recognition Software and Techniques for Biological Image Analysis

The increasing prevalence of automated image acquisition systems is enabling new types of microscopy experiments that generate large image datasets. However, there is a perceived lack of robust image analysis systems required to process these diverse datasets. Most automated image analysis systems are tailored for specific types of microscopy, contrast methods, probes, and even cell types. This imposes significant constraints on experimental design, limiting their application to the narrow set of imaging methods for which they were designed. One of the approaches to address these limitations is pattern recognition, which was originally developed for remote sensing, and is increasingly being applied to the biology domain. This approach relies on training a computer to recognize patterns in images rather than developing algorithms or tuning parameters for specific image processing tasks. The generality of this approach promises to enable data mining in extensive image repositories, and provide objective and quantitative imaging assays for routine use. Here, we provide a brief overview of the technologies behind pattern recognition and its use in computer vision for biological and biomedical imaging. We list available software tools that can be used by biologists and suggest practical experimental considerations to make the best use of pattern recognition techniques for imaging assays

Neuro-Musculoskeletal Mapping for Man-Machine Interfacing

We propose a myoelectric control method based on neural data regression and musculoskeletal modeling. This paradigm uses the timings of motor neuron discharges decoded by high-density surface electromyogram (HD-EMG) decomposition to estimate muscle excitations. The muscle excitations are then mapped into the kinematics of the wrist joint using forward dynamics. The offline tracking performance of the proposed method was superior to that of state-of-the-art myoelectric regression methods based on artificial neural networks in two amputees and in four out of six intact-bodied subjects. In addition to joint kinematics, the proposed data-driven model-based approach also estimated several biomechanical variables in a full feed-forward manner that could potentially be useful in supporting the rehabilitation and training process. These results indicate that using a full forward dynamics musculoskeletal model directly driven by motor neuron activity is a promising approach in rehabilitation and prosthetics to model the series of transformations from muscle excitation to resulting joint function

Man/machine interface based on the discharge timings of spinal motor neurons after targeted muscle reinnervation

The intuitive control of upper - limb prostheses requires a man/machine interface that directly exploits biological signals. Here, we define and experimentally test an offline man/machine interface that takes advantage of the discharge timings of spinal moto r neurons. The motor - neuron behaviour is identified by deconvolution of the electrical activity of muscles reinnervated by nerves of a missing limb in patients with amputation at the shoulder or humeral level. We mapped the series of motor - neuron discharge s into control commands across multiple degrees of freedom via the offline application of direct proportional control, pattern recognition and musculoskeletal modelling. A series of experiments performed on six patients reveal that the man/machine interfac e has superior offline performance than conventional direct electromyographic control applied after targeted muscle innervation. The combination of surgical procedures, decoding and mapping into effective commands constitutes an interface with the output l ayers of the spinal cord circuitry that allows for the intuitive control of multiple degrees of freedom