MrBayes 3.2: efficient Bayesian phylogenetic inference and model choice across a large model space

Since its introduction in 2001, MrBayes has grown in popularity as a software package for Bayesian phylogenetic inference using Markov chain Monte Carlo (MCMC) methods. With this note, we announce the release of version 3.2, a major upgrade to the latest official release presented in 2003. The new version provides convergence diagnostics and allows multiple analyses to be run in parallel with convergence progress monitored on the fly. The introduction of new proposals and automatic optimization of tuning parameters has improved convergence for many problems. The new version also sports significantly faster likelihood calculations through streaming single-instruction-multiple-data extensions (SSE) and support of the BEAGLE library, allowing likelihood calculations to be delegated to graphics processing units (GPUs) on compatible hardware. Speedup factors range from around 2 with SSE code to more than 50 with BEAGLE for codon problems. Checkpointing across all models allows long runs to be completed even when an analysis is prematurely terminated. New models include relaxed clocks, dating, model averaging across time-reversible substitution models, and support for hard, negative, and partial (backbone) tree constraints. Inference of species trees from gene trees is supported by full incorporation of the Bayesian estimation of species trees (BEST) algorithms. Marginal model likelihoods for Bayes factor tests can be estimated accurately across the entire model space using the stepping stone method. The new version provides more output options than previously, including samples of ancestral states, site rates, site d(N)/d(S) rations, branch rates, and node dates. A wide range of statistics on tree parameters can also be output for visualization in FigTree and compatible software.     

BEAGLE: an application programming interface and high-performance computing library for statistical phylogenetics

Phylogenetic inference is fundamental to our understanding of most aspects of the origin and evolution of life, and in recent years, there has been a concentration of interest in statistical approaches such as Bayesian inference and maximum likelihood estimation. Yet, for large data sets and realistic or interesting models of evolution, these approaches remain computationally demanding. High-throughput sequencing can yield data for thousands of taxa, but scaling to such problems using serial computing often necessitates the use of nonstatistical or approximate approaches. The recent emergence of graphics processing units (GPUs) provides an opportunity to leverage their excellent floating-point computational performance to accelerate statistical phylogenetic inference. A specialized library for phylogenetic calculation would allow existing software packages to make more effective use of available computer hardware, including GPUs. Adoption of a common library would also make it easier for other emerging computing architectures, such as field programmable gate arrays, to be used in the future. We present BEAGLE, an application programming interface (API) and library for high-performance statistical phylogenetic inference. The API provides a uniform interface for performing phylogenetic likelihood calculations on a variety of compute hardware platforms. The library includes a set of efficient implementations and can currently exploit hardware including GPUs using NVIDIA CUDA, central processing units (CPUs) with Streaming SIMD Extensions and related processor supplementary instruction sets, and multicore CPUs via OpenMP. To demonstrate the advantages of a common API, we have incorporated the library into several popular phylogenetic software packages. The BEAGLE library is free open source software licensed under the Lesser GPL and available from http://beagle-lib.googlecode.com. An example client program is available as public domain software.     

International field hockey players perform more high-speed running than national-level counterparts

This study compared the activity profile of national and international male field hockey athletes. Sixteen players (mean (±SD) age, stature, and body mass: 22 ± 4 y, 178 ± 8 cm, and 78 ± 9 kg, respectively) competing in the national-level Australian Hockey League (AHL) and 16 players [mean (±SD) age, stature, and body mass: 27 ± 4 y, 179 ± 5 cm, and 77 ± 5 kg, respectively] competing in the international Champions Trophy (CT) tournament participated in this study. Global positioning systems assessed total distance (TD), meters per minute (m·min(-1)), and high-speed running distance (HSR; >4.17 m·s(-1)). Differences in multistage fitness test performance, movement between competition, positions, and halves were assessed using effect size and percent difference ±90% confidence intervals. The CT players had a 10.1% greater multistage fitness test, 13.9% and 42.0% more TD and HSR, respectively, than AHL. During CT, strikers performed 10.1 ± 7.4% less HSR than midfielders and 26.6 ± 8.2% more HSR than defenders. The AHL defenders covered less TD and HSR distance compared with strikers and midfielders (8.1 ± 3.6% and 8.4 ± 2.6%; 36.1 ± 11.1% and 51.5 ± 12.1%, respectively). The AHL strikers, midfielders, and defenders (19.9 ± 8.8%, 32.1 ± 7.9%, and 30.3 ± 10.7%, respectively), all performed less HSR distance than their CT counterparts. Finally, TD decreased from the first to second halves across all positions (6.1-7.5%) in both competitions. International competition increases the running profile of hockey players, with greater HSR at the elite level and positional differences including decreased running during the second half in both competitions.     

Real-time confocal imaging of trafficking of nestin-expressing multipotent stem cells in mouse whiskers in long-term 3-D histoculture

We have previously demonstrated that nestin-expressing multipotent hair follicle stem cells are located above the hair follicle bulge and can differentiate into neurons and other cell types in vitro. The nestin-expressing hair follicle stem cells promoted the recovery of pre-existing axons when they were transplanted to the severed sciatic nerve or injured spinal cord. We have also previously demonstrated that the whisker hair follicle contains nestin-expressing stem cells in the dermal papilla (DP) as well as in the bulge area (BA), but that their origin is in the BA. In the present study, we established the technique of long-term Gelfoam? histoculture of whiskers isolated from transgenic mice in which nestin drives green fluorescent protein (ND-GFP). Confocal imaging was used to monitor ND-GFP-expressing stem cells trafficking in real time between the BA and DP to determine the fate of the stem cells. It was observed over a 2-week period that the stem cells trafficked from the BA toward the DP area and extensively grew out onto Gelfoam? forming nerve-like structures. This new method of long-term histoculture of whiskers from ND-GFP mice will enable the extensive study of the behavior of nestin-expressing multipotent stem cells of the hair follicle.     

The Revised Classification of Eukaryotes

This revision of the classification of eukaryotes, which updates that of Adl et al. [J. Eukaryot. Microbiol. 52 (2005) 399], retains an emphasis on the protists and incorporates changes since 2005 that have resolved nodes and branches in phylogenetic trees. Whereas the previous revision was successful in re‐introducing name stability to the classification, this revision provides a classification for lineages that were then still unresolved. The supergroups have withstood phylogenetic hypothesis testing with some modifications, but despite some progress, problematic nodes at the base of the eukaryotic tree still remain to be statistically resolved. Looking forward, subsequent transformations to our understanding of the diversity of life will be from the discovery of novel lineages in previously under‐sampled areas and from environmental genomic information.     

Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing

We show that comprehensive sequence-function maps obtained by deep sequencing can be used to reprogram interaction specificity and to leapfrog over bottlenecks in affinity maturation by combining many individually small contributions not detectable in conventional approaches. We use this approach to optimize two computationally designed inhibitors against H1N1 influenza hemagglutinin and, in both cases, obtain variants with subnanomolar binding affinity. The most potent of these, a 51-residue protein, is broadly cross-reactive against all influenza group 1 hemagglutinins, including human H2, and neutralizes H1N1 viruses with a potency that rivals that of several human monoclonal antibodies, demonstrating that computational design followed by comprehensive energy landscape mapping can generate proteins with potential therapeutic utility.     

Absolute quantification of somatic DNA alterations in human cancer

We describe a computational method that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. The method, named ABSOLUTE, can detect subclonal heterogeneity and somatic homozygosity, and it can calculate statistical sensitivity for detection of specific aberrations. We used ABSOLUTE to analyze exome sequencing data from 214 ovarian carcinoma tumor-normal pairs. This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12. We also used ABSOLUTE to infer absolute allelic copy-number profiles from 3,155 diverse cancer specimens, revealing that genome-doubling events are common in human cancer, likely occur in cells that are already aneuploid, and influence pathways of tumor progression (for example, with recessive inactivation of NF1 being less common after genome doubling). ABSOLUTE will facilitate the design of clinical sequencing studies and studies of cancer genome evolution and intra-tumor heterogeneity.     

Ramping up mitosis: an AMPKα2-regulated signaling network promotes mitotic progression

In the December 23rd issue of Molecular Cell, Banko et al. (2011) describe a chemical genetic screen that identified 28 novel AMPKα2 direct substrates. A subset of these substrates comprise a signaling network by which AMPK, seemingly independent of cellular energy status, promotes mitotic progression.     

Diversity of Rich Fen Vegetation and Related Plant Specialists in Mountain Refugia of the Iberian Peninsula

In temperate mountains, fens have been reported as relict habitats subject to geographical fragmentation and broad climatic gradients, but few studies have analyzed the influence of these factors on plant diversity. Here we investigate the effect of isolation on the vegetation diversity of rich fens (Caricion davallianae) in the mountains of the Iberian Peninsula, the distribution limit of these habitats in south-western Europe. We used plot-based vegetation data from the Pyrenees and the Cantabrian mountain range to evaluate their regional species-pool, occurrence of specialists, beta-diversity and the effect of geo-climatic variables on their species-richness and species-composition. We found a lower ratio of rare specialists in the Pyrenees than in the Cantabrian range, but similar estimates in the species pools, total species-richness per plot and beta-diversity. The isolation of the two mountain regions resulted in different species assemblages best predicted by summer precipitation and bedrock types, showing region-based differences in the response of vegetation and plant specialists to the environment. The tighter correlation between local climate and diversity estimates in the Cantabrian range suggests relict character of rich fens in that region, where climatic conditions have restricted local distribution of formerly more widely distributed specialists. Although there is no relevant evidence of vegetation impoverishment in that region, historical isolation has probably resulted in the existence of fragmentary plant communities. We conclude that fen vegetation may experience long-time persistence in climatically sub-optimal mountain refugia, but related plant specialists may be sensitive to climatic changes and subject to the extinction of local populations.