Accurate prediction of major histocompatibility complex class II epitopes by sparse representation via ℓ 1-minimization

Background: The major histocompatibility complex (MHC) is responsible for presenting antigens (epitopes) on the surface of antigen-presenting cells (APCs). When pathogen-derived epitopes are presented by MHC class II on an APC surface, T cells may be able to trigger an specific immune response. Prediction of MHC-II epitopes is particularly challenging because the open binding cleft of the MHC-II molecule allows epitopes to bind beyond the peptide binding groove; therefore, the molecule is capable of accommodating peptides of variable length. Among the methods proposed to predict MHC-II epitopes, artificial neural networks (ANNs) and support vector machines (SVMs) are the most effective methods. We propose a novel classification algorithm to predict MHC-II called sparse representation via 1-minimization. Results: We obtained a collection of experimentally confirmed MHC-II epitopes from the Immune Epitope Database and Analysis Resource (IEDB) and applied our 1-minimization algorithm. To benchmark the performance of our proposed algorithm, we compared our predictions against a SVM classifier. We measured sensitivity, specificity abd accuracy; then we used Receiver Operating Characteristic (ROC) analysis to evaluate the performance of our method. The prediction performance of MHC-II epitopes of the 1-minimization algorithm was generally comparable and, in some cases, superior to the standard SVM classification method and overcame the lack of robustness of other methods with respect to outliers. While our method consistently favoured DPPS encoding with the alleles tested, SVM showed a slightly better accuracy when “11-factor” encoding was used. Conclusions: 1-minimization has similar accuracy than SVM, and has additional advantages, such as overcoming the lack of robustness with respect to outliers. With 1-minimization no model selection dependency is involved

Digestion kinetics of dried cereal grains

Grain fermentability largely determines the feed value of grains for ruminants. Our objective was to evaluate the variation in kinetics of gas production of cereal grains and the relationship among gas production, chemical composition and feed value. Eighteen barley, 99 corn, 23 sorghum, and 57 wheat samples were fermented in vitro for 48 h. Gas production was measured with a computerized system and an exponential model was fitted to the data. The impact of the variation in composition and kinetics on the feed value of grains in feedlot rations was assessed with the Cornell Net Carbohydrate and Protein System (CNCPS). Fractional gas rates were significantly different between grains (P\u3c0.001), with a mean and S.D. of 0.24 (0.029) h-1 for barley (n=20), 0.15 (0.026) h-1 for corn (n=98), 0.06 (0.016) h-1 for sorghum (n=23) and 0.26 (0.039) h-1 for wheat (n=57). Fermentation rates were more variable than the chemical components. Fractional rates were poorly correlated with chemical composition within grain with the highest correlations for acid detergent insoluble crude protein (ADICP) (r=-0.31, P\u3c0.01) and ADF (r=-0.27, P\u3c0.01) for corn and neutral detergent insoluble crude protein (NDICP) (r=0.35, P\u3c0.05) for wheat. The impact of the variation in composition and kinetics on the feed value of grains in feedlot rations was assessed. The CNCPS predicted a maximal variation of \u3c2.1 MJ/day and \u3c60 g/day in metabolizable energy (ME) and metabolizable protein (MP) supply from grains, respectively. For sorghum, the fermentation rate was predicted to be a major determinant of the site of starch fermentation. A detailed evaluation of feed values for grains needs to include information on rates of fermentation

Improved feed protein fractionation schemes for formulating rations with the Cornell Net Carbohydrate and Protein System

Adequate predictions of rumen-degradable protein (RDP) and rumen-undegradable protein (RUP) supplies are necessary to optimize performance while minimizing losses of excess nitrogen (N). The objectives of this study were to evaluate the original Cornell Net Carbohydrate Protein System (CNCPS) protein fractionation scheme and to develop and evaluate alternatives designed to improve its adequacy in predicting RDP and RUP. The CNCPS version 5 fractionates CP into 5 fractions based on solubility in protein precipitant agents, buffers, and detergent solutions: A represents the soluble nonprotein N, B1 is the soluble true protein, B2 represents protein with intermediate rates of degradation, B3 is the CP insoluble in neutral detergent solution but soluble in acid detergent solution, and C is the unavailable N. Model predictions were evaluated with studies that measured N flow data at the omasum. The N fractionation scheme in version 5 of the CNCPS explained 78% of the variation in RDP with a root mean square prediction error (RMSPE) of 275 g/d, and 51% of the RUP variation with RMSPE of 248 g/d. Neutral detergent insoluble CP flows were overpredicted with a mean bias of 128 g/d (40% of the observed mean). The greatest improvements in the accuracy of RDP and RUP predictions were obtained with the following 2 alternative schemes. Alternative 1 used the inhibitory in vitro system to measure the fractional rate of degradation for the insoluble protein fraction in which A = nonprotein N, B1 = true soluble protein, B2 = insoluble protein, C = unavailable protein (RDP: R(2) = 0.84 and RMSPE = 167 g/d; RUP: R(2) = 0.61 and RMSPE = 209 g/d), whereas alternative 2 redefined A and B1 fractions as the non-amino-N and amino-N in the soluble fraction respectively (RDP: R(2) = 0.79 with RMSPE = 195 g/d and RUP: R(2) = 0.54 with RMSPE = 225 g/d). We concluded that implementing alternative 1 or 2 will improve the accuracy of predicting RDP and RUP within the CNCPS framework

Model or meal? Farm animal populations as models for infectious diseases of humans

In recent decades, theory addressing the processes that underlie the dynamics of infectious diseases has progressed considerably. Unfortunately, the availability of empirical data to evaluate these theories has not grown at the same pace. Although laboratory animals have been widely used as models at the organism level, they have been less appropriate for addressing issues at the population level. However, farm animal populations can provide empirical models to study infectious diseases at the population level

Development of a mechanistic model to represent the dynamics of liquid flow out of the rumen and to predict the rate of passage of liquid in dairy cattle

A mechanistic and dynamic model was developed to represent the physiological aspects of liquid dynamics in the rumen and to quantitatively predict liquid flow out of the reticulorumen (RR). The model is composed of 2 inflows (water consumption and salivary secretion), one outflow (liquid flow through the reticulo-omasal orifice (ROO), and one in-and-out flow (liquid flux through the rumen wall). We assumed that liquid flow through the ROO was coordinated with the primary reticular contraction, which is characterized by its frequency, duration, and amplitude during eating, ruminating, and resting. A database was developed to predict each component of the model. A random coefficients model was used with studies as a random variable to identify significant variables. Parameters were estimated using the same procedure only if a random study effect was significant. The input variables for the model were dry matter intake, body weight, dietary dry matter, concentrate content in the diet, time spent eating, and time spent ruminating. Total water consumption (kg/d) was estimated as 4.893 x dry matter intake (kg/d), and 20% of the water consumed by drinking was assumed to bypass the RR. The salivary secretion rate was estimated to be 210 g/min during chewing. During ruminating, however, the salivation rate was assumed to be adjusted for the proportion of liquid in the rumen. Resting salivation was exponentially related to dry matter intake. Liquid efflux through the rumen wall was assumed to be the mean value in the database (4.6 kg/h). The liquid outflow rate (kg/h) was assumed to be a product of the frequency of the ROO opening, its duration per opening, and the amount of liquid passed per opening. Simulations of our model suggest that the ROO may open longer for each contraction cycle than had been previously reported (about 3 s) and that it is affected by dry matter intake, body weight, and total digesta in the rumen. When compared with 28 observations in 7 experiments, the model accounted for 40, 70, and 90% of the variation, with root mean square prediction errors of 9.25 kg, 1.84 kg/h, and 0.013 h(-1) for liquid content in the rumen, liquid outflow rate, and fractional rate of liquid passage, respectively. A sensitivity analysis showed that dry matter intake, followed by body weight and time spent eating, were the most important input variables for predicting the dynamics of liquid flow from the rumen. We conclude that this model can be used to understand the factors that affect the dynamics of liquid flow out of the rumen and to predict the fractional rate of liquid passage from the RR in dairy cattle

Evaluation of protein fractionation systems used in formulating rations for dairy cattle

Production efficiency decreases when diets are not properly balanced for protein. Sensitivity analyses of the protein fractionation schemes used by the National Research Council Nutrient Requirement of Dairy Cattle (NRC) and the Cornell Net Carbohydrate and Protein System (CNCPS) were conducted to assess the influence of the uncertainty in feed inputs and the assumptions underlying the CNCPS scheme on metabolizable protein and amino acid predictions. Monte Carlo techniques were used. Two lactating dairy cow diets with low and high protein content were developed for the analysis. A feed database provided by a commercial laboratory and published sources were used to obtain the distributions and correlations of the input variables. Spreadsheet versions of the models were used. Both models behaved similarly when variation in protein fractionation was taken into account. The maximal impact of variation on metabolizable protein from rumen-undegradable protein (RUP) was 2.5 (CNCPS) and 3.0 (NRC) kg/d of allowable milk for the low protein diet, and 3.5 (CNCPS) and 3.9 (NRC) kg/d of allowable milk for the high protein diet. The RUP flows were sensitive to ruminal degradation rates of the B protein fraction in NRC and of the B2 protein fraction in the CNCPS for protein supplements, energy concentrates, and forages. Absorbed Met and Lys flows were also sensitive to intestinal digestibility of RUP, and the CNCPS model was sensitive to acid detergent insoluble crude protein and its assumption of complete unavailability. Neither the intestinal digestibility of the RUP nor the protein degradation rates are routinely measured. Approaches need to be developed to account for their variability. Research is needed to provide better methods for measuring pool sizes and ruminal digestion rates for protein fractionation systems