Analytical advances alleviate model misspecification in non-Brownian multivariate comparative methods.

Adams and Collyer argue that contemporary multivariate (Gaussian) phylogenetic comparative methods are prone to favouring more complex models of evolution and sometimes rotation invariance can be an issue. Here we dissect the concept of rotation invariance and point out that, depending on the understanding, this can be an issue with any method that relies on numerical instead of analytical estimation approaches. We relate this to the ongoing discussion concerning phylogenetic principal component analysis.

Model Selection Performance in Phylogenetic Comparative Methods Under Multivariate Ornstein-Uhlenbeck Models of Trait Evolution.

The advent of fast computational algorithms for phylogenetic comparative methods allows for considering multiple hypotheses concerning the co-adaptation of traits and also for studying if it is possible to distinguish between such models based on contemporary species measurements. Here we demonstrate how one can perform a study with multiple competing hypotheses using mvSLOUCH by analyzing two data sets, one concerning feeding styles and oral morphology in ungulates, and the other concerning fruit evolution in Ferula (Apiaceae). We also perform simulations to determine if it is possible to distinguish between various adaptive hypotheses.

Safety, Tolerability, and Parasite Clearance Kinetics in Controlled Human Malaria Infection after Direct Venous Inoculation of Plasmodium falciparum Sporozoites: A Model for Evaluating New Blood-Stage Antimalarial Drugs.

Plasmodium falciparum sporozoite (PfSPZ) direct venous inoculation (DVI) using cryopreserved, infectious PfSPZ (PfSPZ Challenge [Sanaria, Rockville, Maryland]) is an established controlled human malaria infection model. However, to evaluate new chemical entities with potential blood-stage activity, more detailed data are needed on safety, tolerability, and parasite clearance kinetics for DVI of PfSPZ Challenge with established schizonticidal antimalarial drugs. This open-label, phase Ib study enrolled 16 malaria-naïve healthy adults in two cohorts (eight per cohort).

A Phylogeny-aware GWAS Framework to Correct for Heritable Pathogen Effects on Infectious Disease Traits.

Infectious diseases are particularly challenging for genome-wide association studies (GWAS) because genetic effects from two organisms (pathogen and host) can influence a trait. Traditional GWAS assume individual samples are independent observations. However, pathogen effects on a trait can be heritable from donor to recipient in transmission chains.

Efficient simulation of clinical target response surfaces.

Simulation of combination therapies is challenging due to computational complexity. Either a simple model is used to simulate the response for many combinations of concentration to generate a response surface but parameter variability and uncertainty are neglected and the concentrations are constant-the link to the doses to be administered is difficult to make-or a population pharmacokinetic/pharmacodynamic model is used to predict the response to combination therapy in a clinical trial taking into account the time-varying concentration profile, interindividual variability (IIV), and parameter uncertainty but simulations are limited to only a few selected doses. We devised new algorithms to efficiently search for the combination doses that achieve a predefined efficacy target while taking into account the IIV and parameter uncertainty.

Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART.

The HIV-1 reservoir is the major hurdle to curing HIV-1. However, the impact of the viral genome on the HIV-1 reservoir, i.e.

Fast likelihood calculation for multivariate Gaussian phylogenetic models with shifts.

Phylogenetic comparative methods (PCMs) have been used to study the evolution of quantitative traits in various groups of organisms, ranging from micro-organisms to animal and plant species. A common approach has been to assume a Gaussian phylogenetic model for the trait evolution along the tree, such as a branching Brownian motion (BM) or an Ornstein-Uhlenbeck (OU) process. Then, the parameters of the process have been inferred based on a given tree and trait data for the sampled species.

Automatic generation of evolutionary hypotheses using mixed Gaussian phylogenetic models.

Phylogenetic comparative methods are widely used to understand and quantify the evolution of phenotypic traits, based on phylogenetic trees and trait measurements of extant species. Such analyses depend crucially on the underlying model. Gaussian phylogenetic models like Brownian motion and Ornstein-Uhlenbeck processes are the workhorses of modeling continuous-trait evolution.

A Practical Guide to Estimating the Heritability of Pathogen Traits.

Pathogen traits, such as the virulence of an infection, can vary significantly between patients. A major challenge is to measure the extent to which genetic differences between infecting strains explain the observed variation of the trait. This is quantified by the trait's broad-sense heritability, H2.

Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity.

Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as "per-parasite pathogenicity". Using viral load and CD4+ T-cell measures from 2014 HIV-1 subtype B-infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence-measured as the rate of decline of CD4+ T cells-and per-parasite pathogenicity are heritable from donor to recipient.

Taming the BEAST-A Community Teaching Material Resource for BEAST 2.

Phylogenetics and phylodynamics are central topics in modern evolutionary biology. Phylogenetic methods reconstruct the evolutionary relationships among organisms, whereas phylodynamic approaches reveal the underlying diversification processes that lead to the observed relationships. These two fields have many practical applications in disciplines as diverse as epidemiology, developmental biology, palaeontology, ecology, and linguistics.