Fast and accurate genotype imputation in genome-wide association studies through pre-phasing

The 1000 Genomes Project and disease-specific sequencing efforts are producing large collections of haplotypes that can be used as reference panels for genotype imputation in genome-wide association studies (GWAS). However, imputing from large reference panels with existing methods imposes a high computational burden. We introduce a strategy called 'pre-phasing' that maintains the accuracy of leading methods while reducing computational costs. We first statistically estimate the haplotypes for each individual within the GWAS sample (pre-phasing) and then impute missing genotypes into these estimated haplotypes. This reduces the computational cost because (i) the GWAS samples must be phased only once, whereas standard methods would implicitly repeat phasing with each reference panel update, and (ii) it is much faster to match a phased GWAS haplotype to one reference haplotype than to match two unphased GWAS genotypes to a pair of reference haplotypes. We implemented our approach in the MaCH and IMPUTE2 frameworks, and we tested it on data sets from the Wellcome Trust Case Control Consortium 2 (WTCCC2), the Genetic Association Information Network (GAIN), the Women's Health Initiative (WHI) and the 1000 Genomes Project. This strategy will be particularly valuable for repeated imputation as reference panels evolve.     

Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A

Red blood cells (RBC) have emerged as a novel regulatory cell type endowed with bioactivities toward activated human T cells. Herein we show that the RBC bioactivities act on intracellular pathways initiated by T cell receptor (TCR)-dependent and -independent stimuli, including IL-2, IL-15, and the mixture of phorbol dibutyrate and ionomycin. The RBC bioactivities preserve the antioxidant status and are capable of rescuing activated T cells from cell death induced by serum deprivation. They are not mediated by glycosylphosphatidylinositol-linked receptors or sialic acids, and kinetic studies revealed that they hasten the entrance into the cell cycle. By using cyclosporine A (CsA) and rapamycin (Rapa) we show that the RBC bioactivities are calcineurin-dependent. Thus, treatment of T cells with CsA, but not Rapa, impaired RBC bioactivities, and preincubation of RBC with CsA completely abolished their bioactivities. We have demonstrated that RBC carry out bioactivities that are sensitive to CsA.     

Feature network-driven quadrant mapping for summarizing customer reviews

With the rapid growth of e-commerce, customers increasingly write online reviews of the product they purchase. These customer reviews are one of the most valuable sources of information affecting selection of products or services. Summarizing these customer reviews is becoming an interesting area of research, inspiring researchers to develop a more condensed, concise summarization for users. However, most of the current efforts at summarization are based on general product features without feature’s relationship. As a result, these summaries either ignore feedback from customers or do a poor job of reflecting the opinions expressed in customer reviews. To remedy this summarization shortcoming, we propose a feature network-driven quadrant mapping that captures and incorporates opinions from customer reviews. Our focus is on construction of a feature network, which is based on co-occurrence and sematic similarities, and a quadrant display showing the opinions polarity of feature groups. Moreover, the proposed approach involves clustering similar product features, and thus, it is different from standard text summarization based on abstraction and extraction. The summarized results can help customers better understand the overall opinions about a product.     

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.     

Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies

Genome-wide association is a promising approach to identify common genetic variants that predispose to human disease. Because of the high cost of genotyping hundreds of thousands of markers on thousands of subjects, genome-wide association studies often follow a staged design in which a proportion (pi(samples)) of the available samples are genotyped on a large number of markers in stage 1, and a proportion (pi(samples)) of these markers are later followed up by genotyping them on the remaining samples in stage 2. The standard strategy for analyzing such two-stage data is to view stage 2 as a replication study and focus on findings that reach statistical significance when stage 2 data are considered alone. We demonstrate that the alternative strategy of jointly analyzing the data from both stages almost always results in increased power to detect genetic association, despite the need to use more stringent significance levels, even when effect sizes differ between the two stages. We recommend joint analysis for all two-stage genome-wide association studies, especially when a relatively large proportion of the samples are genotyped in stage 1 (pi(samples) >or= 0.30), and a relatively large proportion of markers are selected for follow-up in stage 2 (pi(markers) >or= 0.01).     

金属离子和脲对背角无齿蚌碱性磷酸酶的影响

研究了多种金属离子对背角无齿蚌碱性磷酸酶（ＡＫＰ）活性的影响，结果表明：Ｎａ＾＋，Ｋ＾＋和Ｌｉ＾＋等一价金属离子没有影响：Ｍｇ＾２＋，Ｃａ＾２＋，Ｂａ＾２＋，Ｎｉ＾２＋，Ｍｎ＾２＋和Ｃｏ＾２＋有激活作用；而Ｃｕ＾２＋，Ｚｎ＾２＋，Ｈｇ＾２＋，Ｃｄ＾２＋及Ａｇ＾＋有抑制作用，脲对ＡＫＰ的变性失活作用，按脲浓度可为低于２ｍｏｌ／Ｌ和高于２ｍｏｌ／Ｌ两种类型，低浓度脲对背角无齿蚌ＡＫＰ活性抑制的动力学表     

Comparison of breeding biology aspects of Fluvicola nengeta (Aves: Tyrannidae) between two nesting sites

Fluvicola nengeta is an insectivorous bird that belongs to the Tyrannidae family, which lives close to bodies of water and can occur in urban areas as well. It makes use of natural and man-made substrates to build its nests. This study aims at describing the reproductive biology of F. nengeta by comparing nests built on vegetation and man-made structures as to their shapes, nest dimensions, building materials, distance from bodies of water and reproductive success. Forty-four nests were found, where 30 were located in vegetation and 14 on man-made structures. Nests did not exhibit any single pattern and were divided into three distinct shapes: closed/globular/base; closed/ovoid/base (45.5%; n = 5 for both) and low cup/base (9%; n = 1). Nests built on man-made structures exhibited a larger amount of anthropic material, such as plastic and paper, instead of plant-derived materials. Nests on man-made structures were found to be higher up from the ground (459.8 ± 46.9 m) and farther from water (232.9 ± 54.8 m) in comparison to those on vegetation (92.2 ± 28.6 m and 7.3 ± 4.7 m, respectively), aside from exhibiting a higher Mayfield reproductive success (37%) when compared to nests built on vegetation (34%). The estimated values of the daily survival rate (DSR) for vegetation nests were 0.997 for the incubation period and 0.928 for the nestling period. In man-made structure nests, DSRs were 0.968 and 0.964, respectively, during the incubation and nestling periods. The period survival rate (PSR) of nests in vegetation was significantly higher than the PSRs of nests in man-made structures during the incubation period. DSRs did not differ between incubation and nestling periods for either nesting sites.