Evaluation of consensus strategies for haplotype phasing

Haplotype phasing is a critical step for many genetic applications but incorrect estimates of phase can negatively impact downstream analyses. One proposed strategy to improve phasing accuracy is to combine multiple independent phasing estimates to overcome the limitations of any individual estimate. However, such a strategy is yet to be thoroughly explored. This study provides a comprehensive evaluation of consensus strategies for haplotype phasing. We explore the performance of different consensus paradigms, and the effect of specific constituent tools, across several datasets with different characteristics and their impact on the downstream task of genotype imputation. Based on the outputs of existing phasing tools, we explore two different strategies to construct haplotype consensus estimators: voting across outputs from multiple phasing tools and multiple outputs of a single non-deterministic tool. We find that the consensus approach from multiple tools reduces SE by an average of 10% compared to any constituent tool when applied to European populations and has the highest accuracy regardless of population ethnicity, sample size, variant density or variant frequency. Furthermore, the consensus estimator improves the accuracy of the downstream task of genotype imputation carried out by the widely used Minimac3, pbwt and BEAGLE5 tools. Our results provide guidance on how to produce the most accurate phasing estimates and the trade-offs that a consensus approach may have. Our implementation of consensus haplotype phasing, consHap, is available freely at https://github.com/ziadbkh/consHap. Supplementary information: Supplementary data are available at Briefings in Bioinformatics online.

Medical robotics simulation framework for application-specific optimal kinematics

Most kinematic structures in robot architectures for medical tasks are not optimal. Further, the workspace and payloads are often oversized which results in high product prices that are not suitable for a clinical technology transfer. To investigate optimal kinematic structures and configurations, we have developed an adaptive simulation framework with an associated workflow for requirement analyses, modelling and simulation of specific robot kinematics. The framework is used to build simple and cost effective medical robot designs and was evaluated in a tool manipulation task where medical instruments had to be positioned precisely and oriented on the patient's body. The model quality is measured based on the maximum workspace coverage according to a configurable scoring metric. The metric generalizes among different human body shapes that are based on anthropometric data from UMTRI Human Shape. This dexterity measure is used to analyze different kinematic structures in simulations using the open source simulation tool V-REP. Therefor we developed simulation and visualization procedures for medical tasks based on a patchwork of size-variant anatomical target regions that can be configured and selectively activated in a motion planning controller. In our evaluations we compared the dexterity scores of a commercial lightweight robot arm with 7 joints to optimized kinematic structures with 6, 7 and 8 joints. Compared to the commercial hardware, we achieved improvements of 59% when using an optimized 6- dimensional robot arm, 64% with the 7-dimensional arm and 96% with an 8-dimensional robot arm. Our results show that simpler robot designs can outperform the typically used commercial robot arms in medical applications where the maximum workspace coverage is essential. Our framework provides the basis for a fully automatic optimization tool of the robot parameters that can be applied to a large variety of problems.

Macroevolutionary patterns of sexual size dimorphism in copepods

Major theories compete to explain the macroevolutionary trends observed in sexual size dimorphism (SSD) in animals. Quantitative genetic theory suggests that the sex under historically stronger directional selection will exhibit greater interspecific variance in size, with covariation between allometric slopes (male to female size) and the strength of SSD across clades. Rensch's rule (RR) also suggests a correlation, but one in which males are always the more size variant sex. Examining free-living pelagic and parasitic Copepoda, we test these competing predictions. Females are commonly the larger sex in copepod species. Comparing clades that vary by four orders of magnitude in their degree of dimorphism, we show that isometry is widespread. As such we find no support for either RR or for covariation between allometry and SSD. Our results suggest that selection on both sexes has been equally important. We next test the prediction that variation in the degree of SSD is related to the adult sex ratio. As males become relatively less abundant, it has been hypothesized that this will lead to a reduction in both inter-male competition and male size. However, the lack of such a correlation across diverse free-living pelagic families of copepods provides no support for this hypothesis. By comparison, in sea lice of the family Caligidae, there is some qualitative support of the hypothesis, males may suffer elevated mortality when they leave the host and rove for sedentary females, and their female-biased SSD is greater than in many free-living families. However, other parasitic copepods which do not appear to have obvious differences in sex-based mate searching risks also show similar or even more extreme SSD, therefore suggesting other factors can drive the observed extremes.