Assessing models for genetic prediction of complex traits: a comparison of visualization and quantitative methods

Background

In silico models have recently been created in order to predict which genetic variants are more likely to contribute to the risk of a complex trait given their functional characteristics. However, there has been no comprehensive review as to which type of predictive accuracy measures and data visualization techniques are most useful for assessing these models.

Methods

We assessed the performance of the models for predicting risk using various methodologies, some of which include: receiver operating characteristic (ROC) curves, histograms of classification probability, and the novel use of the quantile-quantile plot. These measures have variable interpretability depending on factors such as whether the dataset is balanced in terms of numbers of genetic variants classified as risk variants versus those that are not.

Results

We conclude that the area under the curve (AUC) is a suitable starting place, and for models with similar AUCs, violin plots are particularly useful for examining the distribution of the risk scores.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1616-z) contains supplementary material, which is available to authorized users.     

Comparison of Worm Control Strategies in Grazing Sheep in Denmark

Control of nematode parasites with reduced reliance on the use of anthelmintics was studied in 16 ewes with suckling twin lambs on contaminated pasture in Denmark. Ewes and lambs were treated with albendazole at turn-out 3 May. Ewes were removed from the groups on 26 July, and lambs were slaughtered on 11 October. The animals were allocated to 4 groups of 8 lambs and their 4 ewes. Group TS was treated with albendazole at weeks 3, 6 and 8 after turnout and set-stocked; group TM was similarly treated but moved to clean pasture in conjunction with the last drenching; group US was untreated and set-stocked, and group UM was left untreated but moved to clean pasture week 8 after turn-out. Supplementary feed was offered in June and August due to scarcity of pasture. Strategic treatments of ewes and lambs weeks 3, 6 and 8 after turn-out, with or without a move to clean pasture, were highly effective in controlling nematode infections for most of the season. This was reflected in better weight gains and carcass characteristics in the treated compared to untreated lambs, resulting in an average increase in the value of the product by 36%. The effect of moving without treatment (UM) on faecal egg counts was limited but peak pasture infectivity was reduced to less than 10% compared to the set-stocked group and weight gains of lambs were significantly better despite poor feed availability in late season. The study showed that under set-stocked conditions repeated anthelmintic treatments of both ewes and lambs in early season may ensure sufficient nematode control whereas moving animals to clean pasture without dosing was less efficient. The latter may, however, still be a viable option in organic and other production systems where routine use of anthelmintics is banned, particularly if weaning and moving are combined or a second move is performed.     

Investigation of apoptosis in cultured cells infected with equine herpesvirus 1

Many viruses alter different stages of apoptosis of infected cells as a strategy for successful infection. Few studies have addressed mechanisms of equine herpesvirus 1 (EHV-1) strain-induced cell death. We investigated the effect of an abortigenic strain (AR8 strain) on heterologous Madin–Darby bovine kidney cells and homologous equine dermis (ED) cells cell lines. We compared morphologic and biochemical features of early and late apoptosis at different postinfection times. We investigated translocation of phosphatidylserine to the cell surface, nuclear fragmentation and changes in the cytoskeleton using flow cytometry and annexin V/propidium iodide staining, DNA laddering, terminal deoxynucleotidyl transferase UTP nick-end labeling assay and immunofluorescence staining of cytokeratin 18 cleavage. AR8 EVH-1 strain interfered with apoptosis in both cell lines, particularly during the middle stage of the replication cycle; this was more evident in ED cells. Although this antiapoptotic effect has been reported for other alpha herpesviruses, our findings may help elucidate how EHV-1 improves its infectivity during its cycle.     

在中国应用垂直波束雷达监测褐飞虱和其他水稻害虫迁飞的可行性

近年来,可用于昆虫迁飞研究且可自动运行的垂直波束雷达(vertical-looking radar,VLR)的发展使得对迁飞性害虫的周年长期自动监测成为可能。本文提供了我们对能否将这种雷达应用于中国的褐飞虱和其他水稻害虫的监测与预测体系以改善其综合治理的可行性研究结果。以往的研究已经表明,这些害虫一般在300—2000m高度迁飞;而我们根据褐飞虱的雷达和射有效截面的计算结果表明,目前使用的3．2cm波长的VLR对褐飞虱个体目标的最大可检测高度仅约240m;虽然建造一部8．8mm波长的VLR即可覆盖褐飞虱迁飞高度的绝大部分,但其造价和维护费用均过于昂贵。为此,一个更可行的解决方案是,以3．2cm波长的VLR作为包括大多数水稻害虫在内的个体较大的迁飞性害虫的监测工具。     

Functional changes in human leukemic cell line HL-60. A model for myeloid differentiation

Polar solvents induce terminal differentiation in the human promyelocytic leukemia cell line HL-60. The present studies describe the functional changes that accompany the morphologic progression from promyelocytes to bands and poly-morphonuclear leukocytes (PMN) over 9 d of culture in 1.3 percent dimethylsulfoxide (DMSO). As the HL-60 cells mature, the rate of O(2-) production increase 18-fold, with a progressive shortening of the lag time required for activation. Hexosemonophosphate shunt activity rises concomitantly. Ingestin of paraffin oil droplets opsonized with complement or Ig increases 10-fold over 9 d in DMSO. Latex ingestion per cell by each morphologic type does not change significantly, but total latex ingestion by groups of cells increases with the rise in the proportion of mature cells with greater ingestion capacities. Degranulation, as measured by release of β-glucuronidase, lysozyme, and peroxidase, reaches maximum after 3-6 d in DMSO, then declines. HL-60 cells contain no detectable lactoferrin, suggesting that their secondary granules are absent or defective. However, they kill staphylococci by day 6 in DMSO. Morphologically immature cells (days 1-3 in DMSO) are capable of O(2-) generation, hexosemonophosphate shunt activity, ingestion, degranulation, and bacterial killing. Maximal performance of each function by cells incubated in DMSO for longer periods of time is 50-100 percent that of normal PMN. DMSO- induced differentiation of HL-60 cells is a promising model for myeloid development.     

Evolution of a length polymorphism in the human PER3 gene, a component of the circadian system

Period homologue 3 (PER3) is a component of the mammalian circa-dian system, although its precise role is unknown. A biallelic variable number tandem repeat (VNTR) polymorphism exists in human PER3, consisting of 4 or 5 repeats of a 54-bp sequence in a region encoding a putative phosphorylation domain. This polymorphism has previously been reported to associate with diurnal preference ("morningness" and "eveningness") and delayed sleep-phase syndrome. We have investigated the global allele frequencies of this variant in ethnically distinct indigenous populations. All populations were polymorphic, with the shorter (4-repeat) allele ranging in frequency from 0.19 (Papua New Guinea) to 0.89 (Mongolia). To investigate if allele frequency has been influenced by natural selection, the authors 1) tested for a correlation with latitude and mean annual insolation (incident sunlight energy), using classical markers to correct for historical population differentiation; and they 2) compared allele-frequency difference between European American, African American, and East Asian populations, as measured using F(ST), to an empirical null distribution of F(ST)values based on a genome-wide dataset of single nucleotide polymorphisms (SNPs) of presumed neutral loci that were previously typed by The SNP Consortium. The variation in allele frequencies between indigenous populations did not show a pattern that would indicate selective pressure on PER3resulting from day-length variation or mean annual insolation, and the allele-frequency difference between European Americans, African Americans, and East Asians was not an outlier when compared to the distribution for presumed neutral SNPs. We therefore find no evidence for differential or balancing selection in the contemporary pattern of global PER3allele frequencies.