Improving genomic prediction for two Yorkshire populations with a limited size using the single‐step method

In this study, we conducted genomic prediction for two Yorkshire purebred populations (Yichun and Chifeng) from two different provinces of China that both had a limited population size. Two growth traits (age adjusted to 100 kg weight, AGE; back‐fat thickness adjusted to 100 kg weight, BF) and one reproduction trait (total number of piglets born, TNB) were analyzed with four prediction strategies: one‐population BLUP, joint two‐population BLUP, one‐population single‐step BLUP (SSBLUP) and joint two‐population SSBLUP. Our results illustrate that accuracies of genomic estimated breeding values were improved for BF and TNB for the Yichun population and for BF for the Chifeng population by genomic prediction (one‐population SSBLUP and joint two‐population SSBLUP). The accuracy of TNB for the Yichun population was increased two fold when comparing the one‐population SSBLUP to the one‐population BLUP prediction. Meanwhile, prediction biases were dramatically reduced for AGE for the Yichun population and for TNB for the Chifeng population. The conclusions of this study are as follows: first, genomic prediction is useful for improving prediction accuracy for purebred pig breeding farms with a limited population size; second, joint genomic prediction for different populations of the same breed with certain genetic links has the trend to further improve prediction accuracy.     

A global optimization method for prediction of muscle forces of human musculoskeletal system

Inverse dynamic optimization is a popular method for predicting muscle and joint reaction forces within human musculoskeletal joints. However, the traditional formulation of the optimization method does not include the joint reaction moment in the moment equilibrium equation, potentially violating the equilibrium conditions of the joint. Consequently, the predicted muscle and joint reaction forces are coordinate system-dependent. This paper presents an improved optimization method for the prediction of muscle forces and joint reaction forces. In this method, the location of the rotation center of the joint is used as an optimization variable, and the moment equilibrium equation is formulated with respect to the joint rotation center to represent an accurate moment constraint condition. The predicted muscle and joint reaction forces are independent of the joint coordinate system. The new optimization method was used to predict muscle forces of an elbow joint. The results demonstrated that the joint rotation center location varied with applied loading conditions. The predicted muscle and joint reaction forces were different from those predicted by using the traditional optimization method. The results further demonstrated that the improved optimization method converged to a minimum for the objective function that is smaller than that reached by using the traditional optimization method. Therefore, the joint rotation center location should be involved as a variable in an inverse dynamic optimization method for predicting muscle and joint reaction forces within human musculoskeletal joints.     

Predicting the shapes of bones at a joint: application to the shoulder

This paper presents a novel method to explore the intrinsic morphological correlation between the bones of a shoulder joint (humerus and scapula). To model this correlation, canonical correlation analysis (CCA) is used. We also propose a technique to predict a three-dimensional (3D) bone shape from its adjoining segment at a joint based on partial least squares regression (PLS). The high dimensional 3D surface information of a bone is represented by a few variables using principal component analysis, which also captures the pattern of variability of the shapes in our datasets. Our results show that the humerus set and scapula set have highly linear morphological relationship and that the correlation information can be used as a classifier. In this study, primate shoulder bone datasets were categorised into two clusters: great apes (including humans) and monkeys. A leave one out experiment was performed to test the robustness of this prediction method. The prediction behaviour using this method shows statistically significantly better results than using the mean shape from the training set.     

Combinatorial analysis of interacting RNA molecules

Recently several minimum free energy (MFE) folding algorithms for predicting the joint structure of two interacting RNA molecules have been proposed. Their folding targets are interaction structures, that can be represented as diagrams with two backbones drawn horizontally on top of each other such that (1) intramolecular and intermolecular bonds are noncrossing and (2) there is no “zigzag” configuration. This paper studies joint structures with arc-length at least four in which both, interior and exterior stack-lengths are at least two (no isolated arcs). The key idea in this paper is to consider a new type of shape, based on which joint structures can be derived via symbolic enumeration. Our results imply simple asymptotic formulas for the number of joint structures with surprisingly small exponential growth rates. They are of interest in the context of designing prediction algorithms for RNA-RNA interactions.     

Least-squares identification of the dynamic relation between the electromyogram and joint moment

The dynamic relation between surface EMG of an agonist and isometric joint moment is important in models for the prediction of dynamic joint moment from EMG. An efficient approach for determining the best-fitting linear transfer function relating EMG and isometric moment, using a least-squares approach, is presented and illustrated for a second-order model.     

The effect of high-density genotypic data and different methods on joint genomic prediction: A case study in large white pigs

Joint genomic prediction (GP) is an attractive method to improve the accuracy of GP by combining information from multiple populations. However, many factors can negatively influence the accuracy of joint GP, such as differences in linkage disequilibrium phasing between single nucleotide polymorphisms (SNPs) and causal variants, minor allele frequencies and causal variants’ effect sizes across different populations. The objective of this study was to investigate whether the imputed high-density genotype data can improve the accuracy of joint GP using genomic best linear unbiased prediction (GBLUP), single-step GBLUP (ssGBLUP), multi-trait GBLUP (MT-GBLUP) and GBLUP based on genomic relationship matrix considering heterogenous minor allele frequencies across different populations (wGBLUP). Three traits, including days taken to reach slaughter weight, backfat thickness and loin muscle area, were measured on 67 276 Large White pigs from two different populations, for which 3334 were genotyped by SNP array. The results showed that a combined population could substantially improve the accuracy of GP compared with a single-population GP, especially for the population with a smaller size. The imputed SNP data had no effect for single population GP but helped to yield higher accuracy than the medium-density array data for joint GP. Of the four methods, ssGLBUP performed the best, but the advantage of ssGBLUP decreased as more individuals were genotyped. In some cases, MT-GBLUP and wGBLUP performed better than GBLUP. In conclusion, our results confirmed that joint GP could be beneficial from imputed high-density genotype data, and the wGBLUP and MT-GBLUP methods are promising for joint GP in pig breeding.     

Prediction of fingers posture using artificial neural networks

Predicting the hand and fingers posture during grasping tasks is an important issue in the frame of biomechanics. In this paper, a technique based on neural networks is proposed to learn the inverse kinematics mapping between the fingertip 3D position and the corresponding joint angles. Finger movements are obtained by an instrumented glove and are mapped to a multichain model of the hand. From the fingertip desired position, the neural networks allow predicting the corresponding finger joint angles keeping the specific subject coordination patterns. Two sets of movements are considered in this study. The first one, the training set, consisting of free fingers movements is used to construct the mapping between fingertip position and joint angles. The second one, constructed for testing purposes, is composed of a sequence of grasping tasks of everyday-life objects. The maximal mean error between fingertip measured position and fingertip position obtained from simulated joint angles and forward kinematics is 0.99+/-0.76mm for the training set and 1.49+/-1.62mm for the test set. Also, the maximal RMS error of joint angles prediction is 2.85 degrees and 5.10 degrees for the training and test sets respectively, while the maximal mean joint angles prediction error is -0.11+/-4.34 degrees and -2.52+/-6.71 degrees for the training and test sets, respectively. Results relative to the learning and generalization capabilities of this architecture are also presented and discussed.     

A Bayesian approach to joint modeling of matrix-valued imaging data and treatment outcome with applications to depression studies

In this paper, we propose a unified Bayesian joint modeling framework for studying association between a binary treatment outcome and a baseline matrix-valued predictor. Specifically, a joint modeling approach relating an outcome to a matrix-valued predictor through a probabilistic formulation of multilinear principal component analysis is developed. This framework establishes a theoretical relationship between the outcome and the matrix-valued predictor, although the predictor is not explicitly expressed in the model. Simulation studies are provided showing that the proposed method is superior or competitive to other methods, such as a two-stage approach and a classical principal component regression in terms of both prediction accuracy and estimation of association; its advantage is most notable when the sample size is small and the dimensionality in the imaging covariate is large. Finally, our proposed joint modeling approach is shown to be a very promising tool in an application exploring the association between baseline electroencephalography data and a favorable response to treatment in a depression treatment study by achieving a substantial improvement in prediction accuracy in comparison to competing methods.     

Predicting Growth Conditions from Internal Metabolic Fluxes in an In-Silico Model of E. coli

A widely studied problem in systems biology is to predict bacterial phenotype from growth conditions, using mechanistic models such as flux balance analysis (FBA). However, the inverse prediction of growth conditions from phenotype is rarely considered. Here we develop a computational framework to carry out this inverse prediction on a computational model of bacterial metabolism. We use FBA to calculate bacterial phenotypes from growth conditions in E. coli, and then we assess how accurately we can predict the original growth conditions from the phenotypes. Prediction is carried out via regularized multinomial regression. Our analysis provides several important physiological and statistical insights. First, we show that by analyzing metabolic end products we can consistently predict growth conditions. Second, prediction is reliable even in the presence of small amounts of impurities. Third, flux through a relatively small number of reactions per growth source (∼10) is sufficient for accurate prediction. Fourth, combining the predictions from two separate models, one trained only on carbon sources and one only on nitrogen sources, performs better than models trained to perform joint prediction. Finally, that separate predictions perform better than a more sophisticated joint prediction scheme suggests that carbon and nitrogen utilization pathways, despite jointly affecting cellular growth, may be fairly decoupled in terms of their dependence on specific assortments of molecular precursors.     

Prediction of secondary structure for Eco RI endonuclease

The circular dichroism of Eco RI restriction endonuclease was measured to 178 nm and analyzed for secondary structure. The results (33% alpha-helix, 25% beta-sheet, 17% turns, and 25% other structures) compare well with our joint prediction from sequence data.     

Muscle forces predicted using optimization methods are coordinate system dependent

Optimization methods are widely used to predict in vivo muscle forces in musculoskeletal joints. Moment equilibrium at the joint center (usually chosen as the origin of the joint coordinate system) has been used as a constraint condition for optimization procedures and the joint reaction moments were assumed zero. This study, through the use of a three-dimensional elbow model, investigated the effect of coordinate system origin (joint center) location on muscle forces predicted using a nonlinear static optimization method. The results demonstrated that moving the origin of the coordinate system medially and laterally along the flexion-extension axis caused dramatic variations in the predicted muscle forces. For example, moving the origin of the coordinate system from a position 5mm medial to 5mm lateral of the geometric elbow center caused the predicted biceps force to vary from 12% to 46% and the brachialis force to vary from 80% to 34% of the total muscle loading. The joint reaction force reduced by 24% with this medial to lateral variation of the coordinate system origin location. This data revealed that the muscle forces predicted using the optimization method are sensitive to the coordinate system origin location due to the zero joint reaction moment assumption in the moment constraint condition. For accurate prediction of muscle load distributions using optimization methods, it is necessary to determine the accurate coordinate system origin location where the condition of a zero joint reaction moment is satisfied.     

Rectifying postures reconstructed from joint angles to meet constraints.

Postures are often described and modeled using angles between body segments rather than joint coordinates. Models can be used to predict these angles as a function of anthropometry and postural requirements. Postural representation, however, requires the joint coordinates. The use of conventional forward kinematics to derive joint coordinates from predicted angles may violate task constraints, such as the placement of a hand on a target or a foot on a pedal. Errors arise because the anthropometry or other motion characteristics of a subject, for which the prediction is to be made, may differ from the data from which the prediction model was derived. We describe how to rectify model-predicted postures to exactly satisfy such task constraints. We require that the model used for predicting the angles also produce estimates of the variation in these predictions. We show how to alter the initial angle predictions, with the amount of perturbation at each angle dependent on the accuracy of its estimation, so as to exactly satisfy the joint coordinate constraints. Finally, we show in an empirical example that this correction usually produces better overall predictions of posture than those obtained initially.     

Using graded response model for the prediction of prostate cancer risk

Disease risk-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association studies (GWAS) have the potential to be used for disease risk prediction. An important feature of these risk-associated SNPs is their weak individual effect but stronger cumulative effect on disease risk. To date, a stable summary estimate of the joint effect of genetic variants on disease risk prediction is not available. In this study, we propose to use the graded response model (GRM), which is based on the item response theory, for estimating the individual risk that is associated with a set of SNPs. We compare the GRM with a recently proposed risk prediction model called cumulative relative risk (CRR). Thirty-three prostate cancer risk-associated SNPs were originally discovered in GWAS by December 2009. These SNPs were used to evaluate the performance of GRM and CRR for predicting prostate cancer risk in three GWAS populations, including populations from Sweden, Johns Hopkins Hospital, and the National Cancer Institute Cancer Genetic Markers of Susceptibility study. Computational results show that the risk prediction estimates of GRM, compared to CRR, are less biased and more stable.     

PARTS: probabilistic alignment for RNA joinT secondary structure prediction

A novel method is presented for joint prediction of alignment and common secondary structures of two RNA sequences. The joint consideration of common secondary structures and alignment is accomplished by structural alignment over a search space defined by the newly introduced motif called matched helical regions. The matched helical region formulation generalizes previously employed constraints for structural alignment and thereby better accommodates the structural variability within RNA families. A probabilistic model based on pseudo free energies obtained from precomputed base pairing and alignment probabilities is utilized for scoring structural alignments. Maximum a posteriori (MAP) common secondary structures, sequence alignment and joint posterior probabilities of base pairing are obtained from the model via a dynamic programming algorithm called PARTS. The advantage of the more general structural alignment of PARTS is seen in secondary structure predictions for the RNase P family. For this family, the PARTS MAP predictions of secondary structures and alignment perform significantly better than prior methods that utilize a more restrictive structural alignment model. For the tRNA and 5S rRNA families, the richer structural alignment model of PARTS does not offer a benefit and the method therefore performs comparably with existing alternatives. For all RNA families studied, the posterior probability estimates obtained from PARTS offer an improvement over posterior probability estimates from a single sequence prediction. When considering the base pairings predicted over a threshold value of confidence, the combination of sensitivity and positive predictive value is superior for PARTS than for the single sequence prediction. PARTS source code is available for download under the GNU public license at http://rna.urmc.rochester.edu.     

SurvJamda: an R package to predict patients' survival and risk assessment using joint analysis of microarray gene expression data

SurvJamda (Survival prediction by joint analysis of microarray data) is an R package that utilizes joint analysis of microarray gene expression data to predict patients' survival and risk assessment. Joint analysis can be performed by merging datasets or meta-analysis to increase the sample size and to improve survival prognosis. The prognosis performance derived from the combined datasets can be assessed to determine which feature selection approach, joint analysis method and bias estimation provide the most robust prognosis for a given set of datasets. AVAILABILITY: The survJamda package is available at the Comprehensive R Archive Network, http://cran.r-project.org. CONTACT: hyasrebi@yahoo.com.     

Isokinetic elbow joint torques estimation from surface EMG and joint kinematic data: using an artificial neural network model.

Because the relations between electromyographic signal (EMG) and anisometric joint torque remain unpredictable, the aim of this study was to determine the relations between the EMG activity and the isokinetic elbow joint torque via an artificial neural network (ANN) model. This 3-layer feed-forward network was constructed using an error back-propagation algorithm with an adaptive learning rate. The experimental validation was achieved by rectified, low-pass filtered EMG signals from the representative muscles, joint angle and joint angular velocity and measured torque. Learning with a limited set of examples allowed accurate prediction of isokinetic joint torque from novel EMG activities, joint position, joint angular velocity. Sensitivity analysis of the hidden node numbers during the learning and testing phases demonstrated that the choice of numbers of hidden node was not critical except at extreme values of those parameters. Model predictions were well correlated with the experimental data (the mean root-mean-square-difference and correlation coefficient gamma in learning were 0.0290 and 0.998, respectively, and in three different speed testings were 0.1413 and 0.900, respectively). These results suggested that an ANN model can represent the relations between EMG and joint torque/moment in human isokinetic movements. The effect of different adjacent electrode sites was also evaluated and showed the location of electrodes was very important to produce errors in the ANN model.