clusterExperiment and RSEC: A Bioconductor package and framework for clustering of single-cell and other large gene expression datasets

Clustering of genes and/or samples is a common task in gene expression analysis. The goals in clustering can vary, but an important scenario is that of finding biologically meaningful subtypes within the samples. This is an application that is particularly appropriate when there are large numbers of samples, as in many human disease studies. With the increasing popularity of single-cell transcriptome sequencing (RNA-Seq), many more controlled experiments on model organisms are similarly creating large gene expression datasets with the goal of detecting previously unknown heterogeneity within cells. It is common in the detection of novel subtypes to run many clustering algorithms, as well as rely on subsampling and ensemble methods to improve robustness. We introduce a Bioconductor R package, clusterExperiment, that implements a general and flexible strategy we entitle Resampling-based Sequential Ensemble Clustering (RSEC). RSEC enables the user to easily create multiple, competing clusterings of the data based on different techniques and associated tuning parameters, including easy integration of resampling and sequential clustering, and then provides methods for consolidating the multiple clusterings into a final consensus clustering. The package is modular and allows the user to separately apply the individual components of the RSEC procedure, i.e., apply multiple clustering algorithms, create a consensus clustering or choose tuning parameters, and merge clusters. Additionally, clusterExperiment provides a variety of visualization tools for the clustering process, as well as methods for the identification of possible cluster signatures or biomarkers. The R package clusterExperiment is publicly available through the Bioconductor Project, with a detailed manual (vignette) as well as well documented help pages for each function.</div

Rarest of the rare: advances in combining evolutionary distinctiveness and scarcity to inform conservation at biogeographical scales

In an era of global habitat loss and species extinction, conservation biology is increasingly becoming a science of triage. A key approach has been the designation of global biodiversity hotspots – areas of high species richness and endemism – prioritizing regions that are disproportionately valuable. However, traditional hotspot approaches leave absent information on species evolutionary histories. We argue that prioritizing the preservation of evolutionary diversity is one way to maximize genotypic and functional diversity, providing ecosystems with the greatest number of options for dealing with an uncertain future.Global.We review methods for encapsulating phylogenetic diversity and distinctiveness and provide an illustration of how phylogenetic metrics can be extended to include data on geographical rarity and inform conservation prioritization at biogeographic scales.Abundance-weighted metrics of evolutionary diversity can be used to simultaneously prioritize populations, species, habitats and biogeographical regions.Policy makers need to know where scarce conservation funds should be focused to maximize gains and minimize the loss of biological diversity. By incorporating these evolutionary diversity metrics into prioritization schemes, managers can better quantify the valuation of different regions based on evolutionary information.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79366/1/j.1472-4642.2010.00650.x.pd

Edge-Related Loss of Tree Phylogenetic Diversity in the Severely Fragmented Brazilian Atlantic Forest

Deforestation and forest fragmentation are known major causes of nonrandom extinction, but there is no information about their impact on the phylogenetic diversity of the remaining species assemblages. Using a large vegetation dataset from an old hyper-fragmented landscape in the Brazilian Atlantic rainforest we assess whether the local extirpation of tree species and functional impoverishment of tree assemblages reduce the phylogenetic diversity of the remaining tree assemblages. We detected a significant loss of tree phylogenetic diversity in forest edges, but not in core areas of small (<80 ha) forest fragments. This was attributed to a reduction of 11% in the average phylogenetic distance between any two randomly chosen individuals from forest edges; an increase of 17% in the average phylogenetic distance to closest non-conspecific relative for each individual in forest edges; and to the potential manifestation of late edge effects in the core areas of small forest remnants. We found no evidence supporting fragmentation-induced phylogenetic clustering or evenness. This could be explained by the low phylogenetic conservatism of key life-history traits corresponding to vulnerable species. Edge effects must be reduced to effectively protect tree phylogenetic diversity in the severely fragmented Brazilian Atlantic forest

The desmosomal cadherin desmoglein-3 acts as a keratinocyte anti-stress protein via suppression of p53

Desmoglein-3 (Dsg3), the Pemphigus Vulgaris (PV) antigen (PVA), plays an essential role in keratinocyte cell–cell adhesion and regulates various signaling pathways involved in the progression and metastasis of cancer where it is upregulated. We show here that expression of Dsg3 impacts on the expression and function of p53, a key transcription factor governing the responses to cellular stress. Dsg3 depletion increased p53 expression and activity, an effect enhanced by treating cells with UVB, mechanical stress and genotoxic drugs, whilst increased Dsg3 expression resulted in the opposite effects. Such a pathway in the negative regulation of p53 by Dsg3 was Dsg3 specific since neither E-cadherin nor desmoplakin knockdown caused similar effects. Analysis of Dsg3−/− mouse skin also indicated an increase of p53/p21WAF1/CIP1 and cleaved caspase-3 relative to Dsg3+/− controls. Finally, we evaluated whether this pathway was operational in the autoimmune disease PV in which Dsg3 serves as a major antigen involved in blistering pathogenesis. We uncovered increased p53 with diffuse cytoplasmic and/or nuclear staining in the oral mucosa of patients, including cells surrounding blisters and the pre-lesional regions. This finding was verified by in vitro studies where treatment of keratinocytes with PV sera, as well as a characterized pathogenic antibody specifically targeting Dsg3, evoked pronounced p53 expression and activity accompanied by disruption of cell–cell adhesion. Collectively, our findings suggThe study was supported by the Barts and The London School of Medicine and Dentistry and Guizhou Medical University, China. The animal work was supported by Deutsche Forschungsgemeinschaft (TR-SFB 156). Jutamas Uttagomol was supported by a scholarship from Naresuan University, Thailand

Extinction Risk and Diversification Are Linked in a Plant Biodiversity Hotspot

Plant extinction risks in the Cape, South Africa differ from those for vertebrates worldwide, with young and fast-evolving plant lineages marching towards extinction at the fastest rate, but independently of human effects

Ecological correlates of extinction risk in Chinese birds

China is one of the countries with the richest bird biodiversity in the world. Among the 1372 Chinese birds, 146 species are considered threatened and three species are regionally extinct according to the officially released China Biodiversity Red List in 2015. Here, we conducted the first extensive analysis to systematically investigate the patterns and processes of extinction and threat in Chinese birds. We addressed the following four questions. First, is extinction risk randomly distributed among avian families in Chinese birds? Second, which families contain more threatened species than would be expected by chance? Third, which species traits are important in determining the extinction risk in Chinese birds using a multivariate phylogenetic comparative approach? Finally, is the form of the relationship between traits additive or nonadditive (synergistic)? We found that the extinction risk of Chinese birds was not randomly distributed among taxonomic families. The families that contained significantly more threatened species than expected were the hornbills, cranes, pittas, pheasants and hawks and eagles. We obtained eleven species traits that are commonly hypothesized to influence extinction risk from the literature: body size, clutch size, trophic level, mobility, habitat specificity, geographical range size, nest type, nest site, flocking tendency, migrant status and hunting vulnerability. After phylogenetic correction, model selection based on Akaike's information criterion identified the synergistic interaction between body size and hunting vulnerability as the single best correlate of extinction risk in Chinese birds. Our results suggest that, in order to be effective, priority management efforts should be given both to certain extinction-prone families, particularly the hornbills, pelicans, cranes, pittas, pheasants and hawks and eagles, and to bird species with large body size and high hunting vulnerability

Threatened reef corals of the world

10.1371/journal.pone.0034459PLoS ONE73