Pasture Feeding Changes the Bovine Rumen and Milk Metabolome

peer-reviewedThe purpose of this study was to examine the effects of two pasture feeding systems—perennial ryegrass (GRS) and perennial ryegrass and white clover (CLV)—and an indoor total mixed ration (TMR) system on the (a) rumen microbiome; (b) rumen fluid and milk metabolome; and (c) to assess the potential to distinguish milk from different feeding systems by their respective metabolomes. Rumen fluid was collected from nine rumen cannulated cows under the different feeding systems in early, mid and late lactation, and raw milk samples were collected from ten non-cannulated cows in mid-lactation from each of the feeding systems. The microbiota present in rumen liquid and solid portions were analysed using 16S rRNA gene sequencing, while 1H-NMR untargeted metabolomic analysis was performed on rumen fluid and raw milk samples. The rumen microbiota composition was not found to be significantly altered by any feeding system in this study, likely as a result of a shortened adaptation period (two weeks’ exposure time). In contrast, feeding system had a significant effect on both the rumen and milk metabolome. Increased concentrations of volatile fatty acids including acetic acid, an important source of energy for the cow, were detected in the rumen of TMR and CLV-fed cows. Pasture feeding resulted in significantly higher concentrations of isoacids in the rumen. The ruminal fluids of both CLV and GRS-fed cows were found to have increased concentrations of p-cresol, a product of microbiome metabolism. CLV feeding resulted in increased rumen concentrations of formate, a substrate compound for methanogenesis. The TMR feeding resulted in significantly higher rumen choline content, which contributes to animal health and milk production, and succinate, a product of carbohydrate metabolism. Milk and rumen-fluids were shown to have varying levels of dimethyl sulfone in each feeding system, which was found to be an important compound for distinguishing between the diets. CLV feeding resulted in increased concentrations of milk urea. Milk from pasture-based feeding systems was shown to have significantly higher concentrations of hippuric acid, a potential biomarker of pasture-derived milk. This study has demonstrated that 1H-NMR metabolomics coupled with multivariate analysis is capable of distinguishing both rumen-fluid and milk derived from cows on different feeding systems, specifically between indoor TMR and pasture-based diets used in this study

Building and validating biomarkers. Comparison of methods and application to prostate cancer

In the present work it is reviewed the the statistical tools available for the biomarker discovery process. Resampling techniques, feature selection, classifiers and metric to evaluate the performance of the biomarkers is reviewed. All the above concepts are tested, applying them into an appropriate work-flow, in a real prostate cancer study. The aim is to find biomarkes to be able to classify men depending the aggressiveness of the cancer after an intervention, from the analysis of the miRNA expression obtained from qPCR. Three different comparisons are assessed, and in each one a total of 20 models are compared to find the best. The R/Bioconductor CMA package is used to perform the analysis. Potential biomarkers are found, although further studies are recommended before its commercialization or other use

Building and validating biomarkers. Comparison of methods and application to prostate cancer

In the present work it is reviewed the the statistical tools available for the biomarker discovery process. Resampling techniques, feature selection, classifiers and metric to evaluate the performance of the biomarkers is reviewed. All the above concepts are tested, applying them into an appropriate work-flow, in a real prostate cancer study. The aim is to find biomarkes to be able to classify men depending the aggressiveness of the cancer after an intervention, from the analysis of the miRNA expression obtained from qPCR. Three different comparisons are assessed, and in each one a total of 20 models are compared to find the best. The R/Bioconductor CMA package is used to perform the analysis. Potential biomarkers are found, although further studies are recommended before its commercialization or other use

Building and validating biomarkers. Comparison of methods and application to prostate cancer

In the present work it is reviewed the the statistical tools available for the biomarker discovery process. Resampling techniques, feature selection, classifiers and metric to evaluate the performance of the biomarkers is reviewed. All the above concepts are tested, applying them into an appropriate work-flow, in a real prostate cancer study. The aim is to find biomarkes to be able to classify men depending the aggressiveness of the cancer after an intervention, from the analysis of the miRNA expression obtained from qPCR. Three different comparisons are assessed, and in each one a total of 20 models are compared to find the best. The R/Bioconductor CMA package is used to perform the analysis. Potential biomarkers are found, although further studies are recommended before its commercialization or other use

Estudi de paràmetres que determinen la qualitat dels vins escumosos i la seva relació amb l'enfosquiment

[cat] Segons estimació del Consell Regulador de l'any 2012, es van vendre 243 milions d'ampolles de vins escumosos amb denominació d'origen Cava, havent-hi registrats 253 cellers elaboradors de Cava i 163 empreses elaboradores del vi base. Per tant, és un sector econòmic important tant a Catalunya com en altres països, el qual vol oferir el millor producte als consumidors. La indústria elaboradora de vins escumosos considera important tenir paràmetres objectius que permetin estandarditzar la qualitat dels seus productes, i així poder garantir la millor qualitat d'aquests. L'aspecte visual és la primera característica que notem i que pot delectar o generar rebuig, podent influir en la percepció de l'aroma i/o el gust. L’estabilitat del color d'aquests vins en el procés d’elaboració, així com durant la distribució i l’emmagatzematge, és un aspecte de gran interès per les bodegues. El color dels vins escumosos acostuma a atribuir-se als compostos fenòlics procedents del raïm, tot i que hi ha altres substàncies en el medi que també poden contribuir en el procés de l'enfosquiment. Per altre banda, durant la rima les mares de segona fermentació poden alliberar o adsorbir compostos que poden alterar la qualitat visual dels vins, i per tant influir en el fenomen de l'enfosquiment. L’objectiu principal d’aquesta tesi Doctoral és avaluar el paper de les mares sobre el fenomen de l'enfosquiment i els compostos relacionats, així com trobar marcadors químics relacionats amb l'enfosquiment per crear models matemàtics per poder predir el període òptim de consum dels vins escumosos. Per a assolir aquest objectiu es van dissenyar dos mostrejos. Un per conèixer l'efecte de les mares de segona fermentació del Cava sobre l'enfosquiment i els compostos relacionats i l'altre per generar models matemàtics que permetin predir el temps màxim en el vi conservarà les seves propietats òptimes segons les condicions de conservació. En el primer, es va procedir a fer un estudi paral·lel amb dos series de vins comparant el període de rima i el mateix temps de vida comercial conservat en les mateixes condicions de celler. En el segon, es va realitzar un mostreig amb sis series de vins comercials, durant més de dos anys, conservats a diferents temperatures reals d'emmagatzematge (nevera, celler i ambient). No s'ha observat que les mares tinguin un paper destacat en la cinètica de formació de l'enfosquiment. Per altra banda, s'ha identificat el 5-HMF en el Cava i s'ha avaluat com a marcador de qualitat relacionat amb l'enfosquiment. En aquest sentit, aquest compost augmenta linealment amb el temps en el rang de temperatures estudiat. S'ha observat que posseïx bones característiques per ser emprat com a marcador de temps-temperatura, millors que la del clàssic paràmetre A420 i els compostos fenòlics. S'ha estudiat la cinètica de formació del 5-HMF, i a partir dels paràmetres cinètics s'han generat models matemàtics que permeten predir el temps de vida en el que el vi conserva les seves òptimes propietats. Aquests models permetran a les bodegues elaboradores de vins escumosos saber quan de temps els seus vins conservaran les propietats òptimes, així com disposar d'una eina útil per saber com han estat conservats els vins en cas de reclamació.[eng] The sparkling wine wineries consider important to have parameters that allow standardizing the quality of their products, so they can guarantee the best quality of their wines. The appearance is the first characteristic we notice and can generate delight or rejection, and also it can influence the perception of smell and/or taste. The color stability of these wines in the process, as well as during distribution and storage, is something of great interest for the wineries . The color of sparkling wines is usually attributed to phenolic compounds from the grape, although there are other substances in the environment that can also contribute to the browning process. On the other hand, during the second fermentation the lees can release or adsorb compounds that may alter the visual quality of the wines, and thus have influence to the browning phenomenon. The main objective of this thesis is to evaluate the role of the lees on the phenomenon of browning and related compounds, as well as find chemical markers related to the browning in order to create mathematical models to predict the optimum period consumption sparkling wines. It has not been observed that lees have a role in the kinetics of formation of browning. Furthermore, 5-HMF has been identified in Cava and also it has been evaluated as a marker of quality related to browning. In this sense, this compound increases linearly with time in the temperature range studied. It has been observed that possesses good characteristics to be used as a marker as time-temperature parameter, with better properties than the classic A420 and phenolic compounds. We have studied the kinetics of formation of 5-HMF, and from these kinetic parameters were generated mathematical models that allow predicting the lifetime which the wine retains its optimum properties. These models allow sparkling wine producers to know how long their wines will retain their optimum properties and also provide a useful tool to see how the wines have been preserved in case of complaint

Assessing the performance of genome-wide association studies for predicting disease risk.

To date more than 3700 genome-wide association studies (GWAS) have been published that look at the genetic contributions of single nucleotide polymorphisms (SNPs) to human conditions or human phenotypes. Through these studies many highly significant SNPs have been identified for hundreds of diseases or medical conditions. However, the extent to which GWAS-identified SNPs or combinations of SNP biomarkers can predict disease risk is not well known. One of the most commonly used approaches to assess the performance of predictive biomarkers is to determine the area under the receiver-operator characteristic curve (AUROC). We have developed an R package called G-WIZ to generate ROC curves and calculate the AUROC using summary-level GWAS data. We first tested the performance of G-WIZ by using AUROC values derived from patient-level SNP data, as well as literature-reported AUROC values. We found that G-WIZ predicts the AUROC with 0.75). On the other hand, the average GWA study produces a multi-SNP risk predictor with an AUROC of 0.55. Detailed AUROC comparisons indicate that most SNP-derived risk predictions are not as good as clinically based disease risk predictors. All our calculations (ROC curves, AUROCs, explained heritability) are in a publicly accessible database called GWAS-ROCS (http://gwasrocs.ca). The G-WIZ code is freely available for download at https://github.com/jonaspatronjp/GWIZ-Rscript/