Genomic prediction in a multiploid crop: genotype by environment interaction and allele dosage effects on predictive ability in banana

Open Access Journal; Published online: 2 March 2018Improving the efficiency of selection in conventional crossbreeding is a major priority in banana (Musa spp.) breeding. Routine application of classical marker assisted selection (MAS) is lagging in banana due to limitations in MAS tools. Genomic selection (GS) based on genomic prediction models can address some limitations of classical MAS, but the use of GS in banana has not been reported to date. The aim of this study was to evaluate the predictive ability of six genomic prediction models for 15 traits in a multi-ploidy training population. The population consisted of 307 banana genotypes phenotyped under low and high input field management conditions for two crop cycles. The single nucleotide polymorphism (SNP) markers used to fit the models were obtained from genotyping by sequencing (GBS) data. Models that account for additive genetic effects provided better predictions with 12 out of 15 traits. The performance of BayesB model was superior to other models particularly on fruit filling and fruit bunch traits. Models that included averaged environment data were more robust in trait prediction even with a reduced number of markers. Accounting for allele dosage in SNP markers (AD-SNP) reduced predictive ability relative to traditional bi-allelic SNP (BA-SNP), but the prediction trend remained the same across traits. The high predictive values (0.47– 0.75) of fruit filling and fruit bunch traits show the potential of genomic prediction to increase selection efficiency in banana breeding

Lectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema

We have previously shown that the defective ability of alveolar macrophages (AM) to phagocytose apoptotic cells (‘efferocytosis’) in chronic obstructive pulmonary disease/emphysema (COPD) could be therapeutically improved using the C-type lectin, mannose binding lectin (MBL), although the exact mechanisms underlying this effect are unknown. An S-type lectin, galectin-3, is also known to regulate macrophage phenotype and function, via interaction with its receptor CD98. We hypothesized that defective expression of galectin/CD98 would be associated with defective efferocytosis in COPD and that mechanisms would include effects on cytoskeletal remodeling and macrophage phenotype and glutathione (GSH) availability. Galectin-3 was measured by ELISA in BAL from controls, smokers and current/ex-smokers with COPD. CD98 was measured on AM using flow cytometry. We assessed the effects of galectin-3 on efferocytosis, CD98, GSH, actin polymerisation, rac activation, and the involvement of PI3K (using β-actin probing and wortmannin inhibition) in vitro using human AM and/or MH-S macrophage cell line. Significant decreases in BAL galectin-3 and AM CD98 were observed in BAL from both current- and ex-smoker COPD subjects vs controls. Galectin 3 increased efferocytosis via an increase in active GTP bound Rac1. This was confirmed with β-actin probing and the role of PI3K was confirmed using wortmannin inhibition. The increased efferocytosis was associated with increases in available glutathione and expression of CD98. We provide evidence for a role of airway lectins in the failed efferocytosis in COPD, supporting their further investigation as potential macrophage-targeted therapies.Violet R. Mukaro, Johan Bylund, Greg Hodge, Mark Holmes, Hubertus Jersmann, Paul N. Reynolds, Sandra Hodg

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Multidimensional signals and analytic flexibility: Estimating degrees of freedom in human speech analyses

Recent empirical studies have highlighted the large degree of analytic flexibility in data analysis which can lead to substantially different conclusions based on the same data set. Thus, researchers have expressed their concerns that these researcher degrees of freedom might facilitate bias and can lead to claims that do not stand the test of time. Even greater flexibility is to be expected in fields in which the primary data lend themselves to a variety of possible operationalizations. The multidimensional, temporally extended nature of speech constitutes an ideal testing ground for assessing the variability in analytic approaches, which derives not only from aspects of statistical modeling, but also from decisions regarding the quantification of the measured behavior. In the present study, we gave the same speech production data set to 46 teams of researchers and asked them to answer the same research question, resulting insubstantial variability in reported effect sizes and their interpretation. Using Bayesian meta-analytic tools, we further find little to no evidence that the observed variability can be explained by analysts’ prior beliefs, expertise or the perceived quality of their analyses. In light of this idiosyncratic variability, we recommend that researchers more transparently share details of their analysis, strengthen the link between theoretical construct and quantitative system and calibrate their (un)certainty in their conclusions

Preregistration for speech researchers (Brown & Strand, 2022)

Purpose: In the last decade, psychology and other sciences have implemented numerous reforms to improve the robustness of our research, many of which are based on increasing transparency throughout the research process. Among these reforms is the practice of preregistration, in which researchers create a time-stamped and uneditable document before data collection that describes the methods of the study, how the data will be analyzed, the sample size, and many other decisions. The current article highlights the benefits of preregistration with a focus on the specific issues that speech, language, and hearing researchers are likely to encounter, and additionally provides a tutorial for writing preregistrations. Conclusions: Although rates of preregistration have increased dramatically in recent years, the practice is still relatively uncommon in research on speech, language, and hearing. Low rates of adoption may be driven by a lack of understanding of the benefits of preregistration (either generally or for our discipline in particular) or uncertainty about how to proceed if it becomes necessary to deviate from the preregistered plan. Alternatively, researchers may see the benefits of preregistration but not know where to start, and gathering this information from a wide variety of sources is arduous and time consuming. This tutorial addresses each of these potential roadblocks to preregistration and equips readers with tools to facilitate writing preregistrations for research on speech, language, and hearing. Supplemental Material S1. Sample preregistration. Brown, V. A., & Strand, J. F. (2022). Preregistration: Practical considerations for speech, language, and hearing research. Journal of Speech, Language, and Hearing Research. Advance online publication. https://doi.org/10.1044/2022_JSLHR-22-00317 Publisher Note: This article is part of the Forum: Promoting Reproducibility for the Speech, Language, and Hearing Sciences.</p

What accounts for individual differences in susceptibility to the McGurk effect?

The McGurk effect is a classic audiovisual speech illusion in which discrepant auditory and visual syllables can lead to a fused percept (e.g., an auditory /bɑ/ paired with a visual /gɑ/ often leads to the perception of /dɑ/). The McGurk effect is robust and easily replicated in pooled group data, but there is tremendous variability in the extent to which individual participants are susceptible to it. In some studies, the rate at which individuals report fusion responses ranges from 0% to 100%. Despite its widespread use in the audiovisual speech perception literature, the roots of the wide variability in McGurk susceptibility are largely unknown. This study evaluated whether several perceptual and cognitive traits are related to McGurk susceptibility through correlational analyses and mixed effects modeling. We found that an individual's susceptibility to the McGurk effect was related to their ability to extract place of articulation information from the visual signal (i.e., a more fine-grained analysis of lipreading ability), but not to scores on tasks measuring attentional control, processing speed, working memory capacity, or auditory perceptual gradiency. These results provide support for the claim that a small amount of the variability in susceptibility to the McGurk effect is attributable to lipreading skill. In contrast, cognitive and perceptual abilities that are commonly used predictors in individual differences studies do not appear to underlie susceptibility to the McGurk effect