Statistical learning of peptide retention behavior in chromatographic separations: a new kernel-based approach for computational proteomics

<p>Abstract</p> <p>Background</p> <p>High-throughput peptide and protein identification technologies have benefited tremendously from strategies based on tandem mass spectrometry (MS/MS) in combination with database searching algorithms. A major problem with existing methods lies within the significant number of false positive and false negative annotations. So far, standard algorithms for protein identification do not use the information gained from separation processes usually involved in peptide analysis, such as retention time information, which are readily available from chromatographic separation of the sample. Identification can thus be improved by comparing measured retention times to predicted retention times. Current prediction models are derived from a set of measured test analytes but they usually require large amounts of training data.</p> <p>Results</p> <p>We introduce a new kernel function which can be applied in combination with support vector machines to a wide range of computational proteomics problems. We show the performance of this new approach by applying it to the prediction of peptide adsorption/elution behavior in strong anion-exchange solid-phase extraction (SAX-SPE) and ion-pair reversed-phase high-performance liquid chromatography (IP-RP-HPLC). Furthermore, the predicted retention times are used to improve spectrum identifications by a <it>p</it>-value-based filtering approach. The approach was tested on a number of different datasets and shows excellent performance while requiring only very small training sets (about 40 peptides instead of thousands). Using the retention time predictor in our retention time filter improves the fraction of correctly identified peptide mass spectra significantly.</p> <p>Conclusion</p> <p>The proposed kernel function is well-suited for the prediction of chromatographic separation in computational proteomics and requires only a limited amount of training data. The performance of this new method is demonstrated by applying it to peptide retention time prediction in IP-RP-HPLC and prediction of peptide sample fractionation in SAX-SPE. Finally, we incorporate the predicted chromatographic behavior in a <it>p</it>-value based filter to improve peptide identifications based on liquid chromatography-tandem mass spectrometry.</p

Trends in the prevalence of grandparents living with grandchild(ren) in selected European countries and the United States

Research from the United States has shown significant increases in the prevalence of three-generation households and in households consisting solely of grandparents and grandchildren. Such shifts in household composition, which are associated with socio-economic disadvantage, may reflect the activation of grandparents as a latent network of support in response to social and demographic changes such as rising partnership disruption. However, to date, little is known in Europe about trends in grandparent households or whether these households are also likely to be disadvantaged. Moreover, we know little about how the familistic and defamilised policy environments in Europe may affect the activation of such latent kin networks. Employing the Integrated Public Use Microdata Series—International and the Office for National Statistics’ Longitudinal Study for England and Wales, we used multivariate techniques to investigate changes in prevalence over time in co-residence with a grandchild across Austria, England and Wales, France, Greece, Portugal, Romania, and the United States. We expected increases in grandparent households in Portugal and Greece, familistic societies with few public alternatives to family support. However, only Romania (like the US) showed an increase in the percentage of people aged 40 and over co-residing with their grandchildren in three-generation households between the late 1970s and 2002. Given rises in poverty and limited support for low-income families in Romania, rises in grandparent coresidence may reflect a coping strategy among poorer families to increasing financial hardship. Regardless of the trends, grandparent households in all the countries studied remained associated with socio-economic disadvantag

Grandparenting after parental divorce: the association between non-resident parent–child meetings and grandparenting in Italy

Previous studies have shown that parental divorce has negative consequences on parent–child relationships and that these effects extend to relations between grandchildren and their grandparents. After parental divorce, grandchildren have less intense and lower quality relations with their grandparents. Some studies suggest that this negative association between union dissolution in the middle generation and grandparent–grandchild relations is explained by the post-divorce residential arrangements and, to a lesser extent, by the gatekeeping role exercised by the resident parent. The role of the frequency of meetings between the non-resident parent and his/her children, however, has been often overlooked in this literature. Using cross-sectional data from the Italian Family and Social Subject Survey, our study explores the extent to which frequent meetings between non-resident separated or divorced parents and their children below age 14 are correlated with grandparent involvement in looking after their grandchildren. The results show that young children who have very frequent meetings with their non-resident parents are more likely to receive care from their grandparents than are those who meet the non-resident parents once a week or less frequently