Testing of alignment parameters for ancient samples: evaluating and optimizing mapping parameters for ancient samples using the TAPAS tool

High-throughput sequence data retrieved from ancient or other degraded samples has led to unprecedented insights into the evolutionary history of many species, but the analysis of such sequences also poses specific computational challenges. The most commonly used approach involves mapping sequence reads to a reference genome. However, this process becomes increasingly challenging with an elevated genetic distance between target and reference or with the presence of contaminant sequences with high sequence similarity to the target species. The evaluation and testing of mapping efficiency and stringency are thus paramount for the reliable identification and analysis of ancient sequences. In this paper, we present ‘TAPAS’, (Testing of Alignment Parameters for Ancient Samples), a computational tool that enables the systematic testing of mapping tools for ancient data by simulating sequence data reflecting the properties of an ancient dataset and performing test runs using the mapping software and parameter settings of interest. We showcase TAPAS by using it to assess and improve mapping strategy for a degraded sample from a banded linsang (Prionodon linsang), for which no closely related reference is currently available. This enables a 1.8-fold increase of the number of mapped reads without sacrificing mapping specificity. The increase of mapped reads effectively reduces the need for additional sequencing, thus making more economical use of time, resources, and sample material

Optimizing the setup of multienvironmental hybrid wheat yield trials for boosting the selection capability

Abstract The accuracy of genomic prediction increases with increasing heritability, and thus the challenge of optimizing the design of multienvironment yield trials under a limited budget arises. With this in mind, we aimed to find the best of several options to sparsely distribute a fixed number of plots across different environments to increase the accuracy of hybrid performance prediction. We used a comprehensive published genomic and phenotypic data set of 1,604 winter wheat (Triticum aestivum L.) hybrids and compared several commonly used biometric models for phenotypic data analysis in a resampling study to identify the one that most accurately estimated the hybrid performance in different imbalanced trials. Our results showed that when using information about genotypic relationships, genotypic values were more strongly associated with the reference values than when this information was ignored. In addition, a balanced environmental sampling resulted in an adequate characterization of each environment and increased the accuracy for estimating the hybrid performance. One promising design involved dividing the genotypes into equally sized subgroups that were tested in a subset of environments, with the constraint that the subgroups overlapped with respect to the environments. This scenario appears to be particularly appropriate, as it provided both high accuracies in the estimates of genotypic values and had low variability resulting from the data sample used. Thus, we were able to clearly demonstrate the utility for optimizing the design of multienvironment hybrid wheat yield trials in times of genomic selection

Efficacy and Safety of Fosmidomycin-Piperaquine as Nonartemisinin-Based Combination Therapy for Uncomplicated Falciparum Malaria : A Single-Arm, Age De-escalation Proof-of-Concept Study in Gabon

Background. Fosmidomycin-piperaquine is being developed as nonartemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. Methods. The study was a phase 2, single-arm, proof-of-concept study of the efficacy, tolerability, and safety of fosmidomycin-piperaquine for the treatment of uncomplicated Plasmodium falciparum monoinfection in Gabon. Adults and children of both sexes with initial parasite counts between 1000 and 150 000/mu L received oral treatment with fosmidomycin (twice daily doses of 30 mg/kg) and piperaquine (once daily dose of 16 mg/kg) for 3 days and followed-up for 63 days. The primary efficacy endpoint was the per-protocol polymerase chain reaction (PCR)-corrected day 28 adequate clinical and parasitological response (ACPR). Results. One hundred patients were enrolled. The PCR-corrected day 28 ACPR rate was 83/83, or 100% (95% confidence interval, 96-100). Fourteen patients had asexual parasitaemia between day 28 and day 63; all were typed by PCR as new infections. Fosmidomycin-piperaquine therapy led to rapid parasite clearance (median, 36 hours; interquartile range [IQR], 6-60) and fever clearance time (median, 12 hours; IQR, 6-48). The electrocardiogram assessments showed 2 patients with prolonged QT interval >500 msec following study drug administration. The majority of adverse events affected the gastrointestinal and respiratory tracts and were transient and mild to moderate in severity. Conclusions. This is the first report of the use of the combination fosmidomycin-piperaquine. The combination appeared to have high efficacy and be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval