Breast cancer is one of the most frequent cancers among women. Extensive studies into the molecular heterogeneity of breast cancer have produced a plethora of molecular subtype classification and ...prognosis prediction algorithms, as well as numerous gene expression signatures. However, reimplementation of these algorithms is a tedious but important task to enable comparison of existing signatures and classification models between each other and with new models. Here, we present the genefu R/Bioconductor package, a multi-tiered compendium of bioinformatics algorithms and gene signatures for molecular subtyping and prognostication in breast cancer.
The genefu package is available from Bioconductor. http://www.bioconductor.org/packages/devel/bioc/html/genefu.html Source code is also available on Github https://github.com/bhklab/genefu
bhaibeka@uhnresearch.ca
Supplementary data are available at Bioinformatics online.
The survcomp package provides functions to assess and statistically compare the performance of survival/risk prediction models. It implements state-of-the-art statistics to (i) measure the ...performance of risk prediction models; (ii) combine these statistical estimates from multiple datasets using a meta-analytical framework; and (iii) statistically compare the performance of competitive models.
Availability: The R/Bioconductor package survcomp is provided open source under the Artistic-2.0 License with a user manual containing installation, operating instructions and use case scenarios on real datasets. survcomp requires R version 2.13.0 or higher. http://bioconductor.org/packages/release/bioc/html/survcomp.html
Contact:
bhaibeka@jimmy.harvard.edu; mschroed@jimmy.harvard.edu
Supplementary Information:
Supplementary data are available at Bioinformatics online.
Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi) that otherwise consists almost exclusively of plant pathogens. Malassezia are ...typically isolated from warm-blooded animals, are dominant members of the human skin mycobiome and are associated with common skin disorders. To characterize the genetic basis of the unique phenotypes of Malassezia spp., we sequenced the genomes of all 14 accepted species and used comparative genomics against a broad panel of fungal genomes to comprehensively identify distinct features that define the Malassezia gene repertoire: gene gain and loss; selection signatures; and lineage-specific gene family expansions. Our analysis revealed key gene gain events (64) with a single gene conserved across all Malassezia but absent in all other sequenced Basidiomycota. These likely horizontally transferred genes provide intriguing gain-of-function events and prime candidates to explain the emergence of Malassezia. A larger set of genes (741) were lost, with enrichment for glycosyl hydrolases and carbohydrate metabolism, concordant with adaptation to skin's carbohydrate-deficient environment. Gene family analysis revealed extensive turnover and underlined the importance of secretory lipases, phospholipases, aspartyl proteases, and other peptidases. Combining genomic analysis with a re-evaluation of culture characteristics, we establish the likely lipid-dependence of all Malassezia. Our phylogenetic analysis sheds new light on the relationship between Malassezia and other members of Ustilaginomycotina, as well as phylogenetic lineages within the genus. Overall, our study provides a unique genomic resource for understanding Malassezia niche-specificity and potential virulence, as well as their abundance and distribution in the environment and on human skin.
The rapid expansion of the CRISPR toolbox through tagging effector domains to either enzymatically inactive Cas9 (dCas9) or Cas9 nickase (nCas9) has led to several promising new gene editing ...strategies. Recent additions include CRISPR cytosine or adenine base editors (CBEs and ABEs) and the CRISPR prime editors (PEs), in which a deaminase or reverse transcriptase are fused to nCas9, respectively. These tools hold great promise to model and correct disease-causing mutations in animal and plant models. But so far, no widely-available tools exist to automate the design of both BE and PE reagents.
We developed PnB Designer, a web-based application for the design of pegRNAs for PEs and guide RNAs for BEs. PnB Designer makes it easy to design targeting guide RNAs for single or multiple targets on a variant or reference genome from organisms spanning multiple kingdoms. With PnB Designer, we designed pegRNAs to model all known disease causing mutations available in ClinVar. Additionally, PnB Designer can be used to design guide RNAs to install or revert a SNV, scanning the genome with one CBE and seven different ABE PAM variants and returning the best BE to use. PnB Designer is publicly accessible at http://fgcz-shiny.uzh.ch/PnBDesigner/ CONCLUSION: With PnB Designer we created a user-friendly design tool for CRISPR PE and BE reagents, which should simplify choosing editing strategy and avoiding design complications.
Background
Eustachian tube dysfunction is regarded as a ‘black box’ term, reflecting a spectrum of dysfunction. The key to its diagnosis and management is in identifying the aetiology and exact ...pathophysiology of the dysfunction.
Design
We present our retrospective 5‐year results for the technique of transnasal endoscopic balloon dilatation of the cartilaginous part of the Eustachian tube, balloon Eustachian tuboplasty (BET). The indication for treatment is chronic obstructive Eustachian tube dysfunction.
Main outcome measures
Preoperatively, the Eustachian tube score (ETS) was obtained by a clinico‐objective assessment involving tubomanometry (TMM) and reported patient symptom. The measurements were repeated 1, 2, 3, 4 and 5 years postoperatively.
Setting
Tertiary referral centre.
Participants
A total of 622 patients (1076 ears) were treated with BET.
Results
One year after treatment, the Eustachian tube score improved from 3.13 (± 2.47 SD) to 5.75 (± 2.76 SD). The Eustachian tube score improved significantly in 73% of ears. The average Eustachian tube score 2 years after treatment improved from 2.65 (± 2.89 SD) to 6.26 (± 3.07 SD). In 82% of patients, the Eustachian tube score improved significantly at 5 years. The subjective satisfaction of the patients was approximately 80%.
Conclusions
Our long‐term results suggest that BET is a safe and feasible treatment for chronic obstructive Eustachian tube dysfunction with a success rate of more than 70%. This study has important implications for other Eustachian tube‐related clinical entities, such as glue ear management (adults and children), continued grommet insertion and tympanomastoid surgery outcomes.
Mating between different species produces hybrids that are usually asexual and stuck as diploids, but can also lead to the formation of new species. Here, we report the genome sequences of 27 ...isolates of the pathogenic yeast Candida orthopsilosis. We find that most isolates are diploid hybrids, products of mating between two unknown parental species (A and B) that are 5% divergent in sequence. Isolates vary greatly in the extent of homogenization between A and B, making their genomes a mosaic of highly heterozygous regions interspersed with homozygous regions. Separate phylogenetic analyses of SNPs in the A- and B-derived portions of the genome produces almost identical trees of the isolates with four major clades. However, the presence of two mutually exclusive genotype combinations at the mating type locus, and recombinant mitochondrial genomes diagnostic of inter-clade mating, shows that the species C. orthopsilosis does not have a single evolutionary origin but was created at least four times by separate interspecies hybridizations between parents A and B. Older hybrids have lost more heterozygosity. We also identify two isolates with homozygous genomes derived exclusively from parent A, which are pure non-hybrid strains. The parallel emergence of the same hybrid species from multiple independent hybridization events is common in plant evolution, but is much less documented in pathogenic fungi.
In-situ analyses reveal the presence of hydrogen within calcium sulfate veins crosscutting the sediments found in Gale crater. Laboratory experiments were performed to calibrate the hydrogen signal ...measured by laser induced breakdown spectroscopy (LIBS) in a range applicable to martian data. The analyses indicate that all veins targeted so far at Gale consist predominantly of bassanite which most likely formed by dehydration of gypsum. This scenario suggests that the percolating water produced gypsum, possibly by hydration of anhydrite in aqueous solution, and remained at temperatures below ∼60 °C at that time. Desiccating conditions followed, consistent with a hyperarid climate and favored by burial or impacts. Additionally, anhydrite with lesser bassanite has been found by XRD in samples of sediments hosting the veins. Our result suggests bassanite is likely found in the veins and anhydrite may be more common as a fine-grained component within the sediments.
•Experiments on calcium sulfate pellets were performed to calibrate the LIBS hydrogen signal.•Bright veins analyzed in situ at Gale crater are made predominantly of bassanite.•Bassanite could have resulted from the desiccation of gypsum.
Abstract
Engineering non-linear hybrid light-matter states in tailored lattices is a central research strategy for the simulation of complex Hamiltonians. Excitons in atomically thin crystals are an ...ideal active medium for such purposes, since they couple strongly with light and bear the potential to harness giant non-linearities and interactions while presenting a simple sample-processing and room temperature operability. We demonstrate lattice polaritons, based on an open, high-quality optical cavity, with an imprinted photonic lattice strongly coupled to excitons in a WS
2
monolayer. We experimentally observe the emergence of the canonical band-structure of particles in a one-dimensional lattice at room temperature, and demonstrate frequency reconfigurability over a spectral window exceeding 85 meV, as well as the systematic variation of the nearest-neighbour coupling, reflected by a tunability in the bandwidth of the p-band polaritons by 7 meV. The technology presented in this work is a critical demonstration towards reconfigurable photonic emulators operated with non-linear photonic fluids, offering a simple experimental implementation and working at ambient conditions.
The Mars Science Laboratory Curiosity rover is traversing a sequence of stratified sedimentary rocks in Gale crater that contain varied eolian, fluviodeltaic, and lake deposits, with phyllosilicates, ...iron oxides, and sulfate salts. Here, we report the chloride salt distribution along the rover traverse. Chlorine is detected at low levels (<3 wt.%) in soil and rock targets with multiple MSL instruments. Isolated fine‐scale observations of high chlorine (up to ≥15 wt.% Cl), detected using the ChemCam instrument, are associated with elevated Na2O and interpreted as halite grains or cements in bedrock. Halite is also interpreted at the margins of veins and in nodular, altered textures. We have not detected halite in obvious evaporitic layers. Instead, its scattered distribution indicates that chlorides emplaced earlier in particular members of the Murray formation were remobilized and reprecipitated by later groundwaters within Murray formation mudstones and in diagenetic veins and nodules.
Plain Language Summary
Chlorine is measured in soils and rocks in Gale crater by multiple instruments on the Mars Science Laboratory Curiosity rover. Fine‐scale points of enriched chlorine are detected by the ChemCam instrument in bedrock, nodules, and at the margins of veins in the Murray formation. Chlorine content is correlated with weight percent Na2O indicating halite composition, corroborated by CheMin and SAM data. The scattered distribution of chlorides in the Murray formation indicates they were dissolved by later groundwaters then recrystallized. The chlorides may have been emplaced as small‐scale primary deposits in particular members of the Murray formation, consistent with varying salinity in the waters that deposited the Murray.
Key Points
Isolated Cl enrichments in bedrock, in nodular textures, and at calcium sulfate vein margins, correlated with Na, indicate halite
Mapping of Cl along the Curiosity traverse in Gale Crater indicates Cl enrichments are more common in select Murray formation members
The scattered, isolated occurrences of chlorides are consistent with late groundwater reworking and remobilization of original deposits
PDF
