Regression models using the LINEX loss to predict lower bounds for the number of points for approximating planar contour shapes.

Researchers in statistical shape analysis often analyze outlines of objects. Even though these contours are infinite-dimensional in theory, they must be discretized in practice. When discretizing, it is important to reduce the number of sampling points considerably to reduce computational costs, but to not use too few points so as to result in too much approximation error. Unfortunately, determining the minimum number of points needed to achieve sufficiently approximate the contours is computationally expensive. In this paper, we fit regression models to predict these lower bounds using characteristics of the contours that are computationally cheap as predictor variables. However, least squares regression is inadequate for this task because it treats overestimation and underestimation equally, but underestimation of lower bounds is far more serious. Instead, to fit the models, we use the LINEX loss function, which allows us to penalize underestimation at an exponential rate while penalizing overestimation only linearly. We present a novel approach to select the shape parameter of the loss function and tools for analyzing how well the model fits the data. Through validation methods, we show that the LINEX models work well for reducing the underestimation for the lower bounds.

An investigation of tuberculosis progression revealing the role of macrophages apoptosis via sensitivity and bifurcation analysis.

Mycobacterium tuberculosis infection features various disease outcomes: clearance, latency, active disease, and latent tuberculosis infection (LTBI) reactivation. Identifying the decisive factors for disease outcomes and progression is crucial to elucidate the macrophages-tuberculosis interaction and provide insights into therapeutic strategies. To achieve this goal, we first model the disease progression as a dynamical shift among different disease outcomes, which are characterized by various steady states of bacterial concentration. The causal mechanisms of steady-state transitions can be the occurrence of transcritical and saddle-node bifurcations, which are induced by slowly changing parameters. Transcritical bifurcation, occurring when the basic reproduction number equals to one, determines whether the infection clears or spreads. Saddle-node bifurcation is the key mechanism to create and destroy steady states. Based on these two steady-state transition mechanisms, we carry out two sample-based sensitivity analyses on transcritical bifurcation conditions and saddle-node bifurcation conditions. The sensitivity analysis results suggest that the macrophage apoptosis rate is the most significant factor affecting the transition in disease outcomes. This result agrees with the discovery that the programmed cell death (apoptosis) plays a unique role in the complex microorganism-host interplay. Sensitivity analysis narrows down the parameters of interest, but cannot answer how these parameters influence the model outcomes. To do this, we employ bifurcation analysis and numerical simulation to unfold various disease outcomes induced by the variation of macrophage apoptosis rate. Our findings support the hypothesis that the regulation mechanism of macrophage apoptosis affects the host immunity against tuberculosis infection and tuberculosis virulence. Moreover, our mathematical results suggest that new treatments and/or vaccines that regulate macrophage apoptosis in combination with weakening bacillary viability and/or promoting adaptive immunity could have therapeutic value.

A mathematical representation of protein binding sites using structural dispersion of atoms from principal axes for classification of binding ligands.

Many researchers have studied the relationship between the biological functions of proteins and the structures of both their overall backbones of amino acids and their binding sites. A large amount of the work has focused on summarizing structural features of binding sites as scalar quantities, which can result in a great deal of information loss since the structures are three-dimensional. Additionally, a common way of comparing binding sites is via aligning their atoms, which is a computationally intensive procedure that substantially limits the types of analysis and modeling that can be done. In this work, we develop a novel encoding of binding sites as covariance matrices of the distances of atoms to the principal axes of the structures. This representation is invariant to the chosen coordinate system for the atoms in the binding sites, which removes the need to align the sites to a common coordinate system, is computationally efficient, and permits the development of probability models. These can then be used to both better understand groups of binding sites that bind to the same ligand and perform classification for these ligand groups. We demonstrate the utility of our method for discrimination of binding ligand through classification studies with two benchmark datasets using nearest mean and polytomous logistic regression classifiers.

Nonparametric Bootstrap of Sample Means of Positive-Definite Matrices with an Application to Diffusion-Tensor-Imaging Data Analysis.

This paper presents nonparametric two-sample bootstrap tests formeans of randomsymmetric positivedefinite (SPD) matrices according to two differentmetrics: the Frobenius (or Euclidean)metric, inherited from the embedding of the set of SPD metrics in the Euclidean set of symmetric matrices, and the canonical metric, which is defined without an embedding and suggests an intrinsic analysis. A fast algorithm is used to compute the bootstrap intrinsic means in the case of the latter. The methods are illustrated in a simulation study and applied to a two-group comparison of means of diffusion tensors (DTs) obtained from a single voxel of registered DT images of children in a dyslexia study.

Protein surface matching by combining local and global geometric information.

Comparison of the binding sites of proteins is an effective means for predicting protein functions based on their structure information. Despite the importance of this problem and much research in the past, it is still very challenging to predict the binding ligands from the atomic structures of protein binding sites. Here, we designed a new algorithm, TIPSA (Triangulation-based Iterative-closest-point for Protein Surface Alignment), based on the iterative closest point (ICP) algorithm. TIPSA aims to find the maximum number of atoms that can be superposed between two protein binding sites, where any pair of superposed atoms has a distance smaller than a given threshold. The search starts from similar tetrahedra between two binding sites obtained from 3D Delaunay triangulation and uses the Hungarian algorithm to find additional matched atoms. We found that, due to the plasticity of protein binding sites, matching the rigid body of point clouds of protein binding sites is not adequate for satisfactory binding ligand prediction. We further incorporated global geometric information, the radius of gyration of binding site atoms, and used nearest neighbor classification for binding site prediction. Tested on benchmark data, our method achieved a performance comparable to the best methods in the literature, while simultaneously providing the common atom set and atom correspondences.