bluuebunny/crossref_metadata_2025_split huggingface dataset:
A weighted exact test for mutually exclusive mutations in cancer
Authors: Leiserson Mark DM , Reyna Matthew A , Raphael Benjamin J 
Published: September 2016

Abstract

Motivation
The somatic mutations in the pathways that drive cancer development tend to be mutually exclusive across tumors, providing a signal for distinguishing driver mutations from a larger number of random passenger mutations. This mutual exclusivity signal can be confounded by high and highly variable mutation rates across a cohort of samples. Current statistical tests for exclusivity that incorporate both per-gene and per-sample mutational frequencies are computationally expensive and have limited precision.

Results
We formulate a weighted exact test for assessing the significance of mutual exclusivity in an arbitrary number of mutational events. Our test conditions on the number of samples with a mutation as well as per-event, per-sample mutation probabilities. We provide a recursive formula to compute P-values for the weighted test exactly as well as a highly accurate and efficient saddlepoint approximation of the test. We use our test to approximate a commonly used permutation test for exclusivity that conditions on per-event, per-sample mutation frequencies. However, our test is more efficient and it recovers more significant results than the permutation test. We use our Weighted Exclusivity Test (WExT) software to analyze hundreds of colorectal and endometrial samples from The Cancer Genome Atlas, which are two cancer types that often have extremely high mutation rates. On both cancer types, the weighted test identifies sets of mutually exclusive mutations in cancer genes with fewer false positives than earlier approaches.

Availability and Implementation
See http://compbio.cs.brown.edu/projects/wext for software.

Contact
braphael@cs.brown.edu

Supplementary information
Supplementary data are available at Bioinformatics online.
iReMet-flux: constraint-based approach for integrating relative metabolite levels into a stoichiometric metabolic models
Authors: Sajitz-Hermstein Max , Töpfer Nadine , Kleessen Sabrina , Fernie Alisdair R , Nikoloski Zoran 
Published: September 2016

Abstract

Motivation
Understanding the rerouting of metabolic reaction fluxes upon perturbations has the potential to link changes in molecular state of a cellular system to alteration of growth. Yet, differential flux profiling on a genome-scale level remains one of the biggest challenges in systems biology. This is particularly relevant in plants, for which fluxes in autotrophic growth necessitate time-consuming instationary labeling experiments and costly computations, feasible for small-scale networks.

Results
Here we present a computationally and experimentally facile approach, termed iReMet-Flux, which integrates relative metabolomics data in a metabolic model to predict differential fluxes at a genome-scale level. Our approach and its variants complement the flux estimation methods based on radioactive tracer labeling. We employ iReMet-Flux with publically available metabolic profiles to predict reactions and pathways with altered fluxes in photo-autotrophically grown Arabidopsis and four photorespiratory mutants undergoing high-to-low CO2 acclimation. We also provide predictions about reactions and pathways which are most strongly regulated in the investigated experiments. The robustness and variability analyses, tailored to the formulation of iReMet-Flux, demonstrate that the findings provide biologically relevant information that is validated with external measurements of net CO2 exchange and biomass production. Therefore, iReMet-Flux paves the wave for mechanistic dissection of the interplay between pathways of primary and secondary metabolisms at a genome-scale.

Availability and Implementation
The source code is available from the authors upon request.

Contact
nikoloski@mpimp-golm.mpg.de

Supplementary information
Supplementary data are available at Bioinformatics online.
MetaProb: accurate metagenomic reads binning based on probabilistic sequence signatures
Authors: Girotto Samuele , Pizzi Cinzia , Comin Matteo 
Published: September 2016

Abstract

Motivation
Sequencing technologies allow the sequencing of microbial communities directly from the environment without prior culturing. Taxonomic analysis of microbial communities, a process referred to as binning, is one of the most challenging tasks when analyzing metagenomic reads data. The major problems are the lack of taxonomically related genomes in existing reference databases, the uneven abundance ratio of species and the limitations due to short read lengths and sequencing errors.

Results
MetaProb is a novel assembly-assisted tool for unsupervised metagenomic binning. The novelty of MetaProb derives from solving a few important problems: how to divide reads into groups of independent reads, so that k-mer frequencies are not overestimated; how to convert k-mer counts into probabilistic sequence signatures, that will correct for variable distribution of k-mers, and for unbalanced groups of reads, in order to produce better estimates of the underlying genome statistic; how to estimate the number of species in a dataset. We show that MetaProb is more accurate and efficient than other state-of-the-art tools in binning both short reads datasets (F-measure 0.87) and long reads datasets (F-measure 0.97) for various abundance ratios. Also, the estimation of the number of species is more accurate than MetaCluster. On a real human stool dataset MetaProb identifies the most predominant species, in line with previous human gut studies.

Availability and Implementation
https://bitbucket.org/samu661/metaprob

Contacts
cinzia.pizzi@dei.unipd.it or comin@dei.unipd.it

Supplementary information
Supplementary data are available at Bioinformatics online.
A program for verification of phylogenetic network models
Authors: Gunawan Andreas DM , Lu Bingxin , Zhang Louxin 
Published: September 2016

Abstract

Motivation
Genetic material is transferred in a non-reproductive manner across species more frequently than commonly thought, particularly in the bacteria kingdom. On one hand, extant genomes are thus more properly considered as a fusion product of both reproductive and non-reproductive genetic transfers. This has motivated researchers to adopt phylogenetic networks to study genome evolution. On the other hand, a gene’s evolution is usually tree-like and has been studied for over half a century. Accordingly, the relationships between phylogenetic trees and networks are the basis for the reconstruction and verification of phylogenetic networks. One important problem in verifying a network model is determining whether or not certain existing phylogenetic trees are displayed in a phylogenetic network. This problem is formally called the tree containment problem. It is NP-complete even for binary phylogenetic networks.

Results
We design an exponential time but efficient method for determining whether or not a phylogenetic tree is displayed in an arbitrary phylogenetic network. It is developed on the basis of the so-called reticulation-visible property of phylogenetic networks.

Availability and Implementation
A C-program is available for download on http://www.math.nus.edu.sg/∼matzlx/tcp_package.

Contact
matzlx@nus.edu.sg

Supplementary information
Supplementary data are available at Bioinformatics online.
Barley (Hordeum vulgare ) circadian clock genes can respond rapidly to temperature in an EARLY FLOWERING 3 -dependent manner
Authors: Ford Brett , Deng Weiwei , Clausen Jenni , Oliver Sandra , Boden Scott , Hemming Megan , Trevaskis Ben 
Published: September 2016

Abstract
An increase in global temperatures will impact future crop yields. In the cereal crops wheat and barley, high temperatures accelerate reproductive development, reducing the number of grains per plant and final grain yield. Despite this relationship between temperature and cereal yield, it is not clear what genes and molecular pathways mediate the developmental response to increased temperatures. The plant circadian clock can respond to changes in temperature and is important for photoperiod-dependent flowering, and so is a potential mechanism controlling temperature responses in cereal crops. This study examines the relationship between temperature, the circadian clock, and the expression of flowering-time genes in barley ( Hordeum vulgare ), a crop model for temperate cereals. Transcript levels of barley core circadian clock genes were assayed over a range of temperatures. Transcript levels of core clock genes CCA1 , GI , PRR59 , PRR73, PRR95 , and LUX are increased at higher temperatures. CCA1 and PRR73 respond rapidly to a decrease in temperature whereas GI and PRR59 respond rapidly to an increase in temperature. The response of GI and the PRR genes to changes in temperature is lost in the elf3 mutant indicating that their response to temperature may be dependent on a functional ELF3 gene.
Negative mood influences default mode network functional connectivity in patients with chronic low back pain: implications for functional neuroimaging biomarkers
Authors: Letzen Janelle E. , Robinson Michael E. 
Published: September 2016

Abstract
The default mode network (DMN) has been proposed as a biomarker for several chronic pain conditions. Default mode network functional connectivity (FC) is typically examined during resting-state functional neuroimaging, in which participants are instructed to let thoughts wander. However, factors at the time of data collection (eg, negative mood) that might systematically impact pain perception and its brain activity, influencing the application of the DMN as a pain biomarker, are rarely reported. This study measured whether positive and negative moods altered DMN FC patterns in patients with chronic low back pain (CLBP), specifically focusing on negative mood because of its clinical relevance. Thirty-three participants (CLBP = 17) underwent resting-state functional magnetic resonance imaging scanning before and after sad and happy mood inductions, and rated levels of mood and pain intensity at the time of scanning. Two-way repeated-measures analysis of variances were conducted on resting-state functional connectivity data. Significant group (CLBP > healthy controls) × condition (sadness > baseline) interaction effects were identified in clusters spanning parietal operculum/postcentral gyrus, insular cortices, anterior cingulate cortex, frontal pole, and a portion of the cerebellum (P
FDR < 0.05). However, only 1 significant cluster covering a portion of the cerebellum was identified examining a two-way repeated-measures analysis of variance for happiness > baseline (P
FDR < 0.05). Overall, these findings suggest that DMN FC is affected by negative mood in individuals with and without CLBP. It is possible that DMN FC seen in patients with chronic pain is related to an affective dimension of pain, which is important to consider in future neuroimaging biomarker development and implementation.
Radiation and hybridization of the Little Devil poison frog (Oophaga sylvatica) in Ecuador
Authors: Roland Alexandre B. , Santos Juan C. , Carriker Bella C. , Caty Stephanie N. , Tapia Elicio E. , Coloma Luis A. , O’Connell Lauren A. 
Published: September 2016

AbstractGeographic variation of color pattern in the South American poison frogs (Dendrobatidae) is an intriguing evolutionary phenomenon. These chemically defended anurans use bright aposematic colors to warn potential predators of their unpalatibility. However, aposematic signals are frequency-dependent and individuals deviating from a local model are at a higher risk of predation. The well-known examples of Batesian and Müllerian mimics, hymenopterans (wasps and bees) andHeliconiusbutterflies, both support the benefits of unique models with relatively high frequencies. However, extreme diversity in the aposematic signal has been documented in the poison frogs of the genusDendrobates, especially in theOophagasubgenus. Here we investigate the phylogenetic and genomic differentiations among populations ofOophaga sylvatica, which exhibit one of the highest phenotypic diversification among poison frogs. Using a combination of PCR amplicons (mitochondrial and nuclear markers) and genome wide markers from a double-digested RAD data set, we characterize 13 populations (12 monotypic and 1 polytypic) across theO. sylvaticadistribution. These populations are mostly separated in two lineages distributed in the Northern and the Southern part of their range in Ecuador. We found relatively low genetic differentiation within each lineage, despite considerable phenotypic variation, and evidence suggesting ongoing gene flow and genetic admixture among some populations of the Northern lineage. Overall these data suggest that phenotypic diversification and novelty in aposematic coloration can arise in secondary contact zones even in systems where phenotypes are subject to strong stabilizing selection.
QCAT: testing causality of variants using only summary association statistics
Authors: Lee Donghyung , Bigdeli T. Bernard , Vladimirov Vladimir I. , Fanous Ayman H. , Bacanu Silviu-Alin 
Published: September 2016

ABSTRACTGenome-wide and, very soon, sequencing association studies, might yield multiple regions harbouring interesting association signals. Given that each region encompasses numerous variants in high linkage disequilibrium, it is not clear which are i) truly causal or ii) just reasonably close to the causal ones. Researchers proposed many methods to predict, albeit not test, the causal SNPs in a region, a process commonly denoted as fine-mapping. Unfortunately, all existing fine-mapping methods output posterior causality probabilities assuming that causal SNPs are among those already measured in the study, or have been catalogued elsewhere. However, due to technological and computational obstacles in calling many types of genetic variants, such assumption is not realistic. We propose a novel method/software, denoted as Quasi-CAausality Test (QCAT), for testing (not just predicting) the causality of any catalogued genetic variant. QCAT i) makes no assumption that causal variants are among catalogued variants, and ii) makes use of easily available summary statistics from genetic studies, e.g. variant association Z-scores, to make statistical inferences. The proposed statistical test controls the type I error at or below the desired level. Its practical application to well-known smoking association signals provide some insightful results. The QCAT software is publically available at:http://dleelab.github.io/qcat/
Carry‐over effects on the annual cycle of a migratory seabird: an experimental study
Authors: Fayet Annette L. , Freeman Robin , Shoji Akiko , Kirk Holly L. , Padget Oliver , Perrins Chris M. , Guilford Tim 
Published: September 2016

SummaryLong‐lived migratory animals must balance the cost of current reproduction with their own condition ahead of a challenging migration and future reproduction. In these species, carry‐over effects, which occur when events in one season affect the outcome of the subsequent season, may be particularly exacerbated. However, how carry‐over effects influence future breeding outcomes and whether (and how) they also affect behaviour during migration and wintering is unclear.Here we investigate carry‐over effects induced by a controlled, bidirectional manipulation of the duration of reproductive effort on the migratory, wintering and subsequent breeding behaviour of a long‐lived migratory seabird, the Manx shearwaterPuffinus puffinus. By cross‐fostering chicks of different age between nests, we successfully prolonged or shortened by ∼25% the chick‐rearing period of 42 breeding pairs. We tracked the adults with geolocators over the subsequent year and combined migration route data with at‐sea activity budgets obtained from high‐resolution saltwater‐immersion data. Migratory behaviour was also recorded during non‐experimental years (the year before and/or two years after manipulation) for a subset of birds, allowing comparison between experimental and non‐experimental years within treatment groups.All birds cared for chicks until normal fledging age, resulting in birds with a longer breeding period delaying their departure on migration; however, birds that finished breeding earlier did not start migrating earlier. Increased reproductive effort resulted in less time spent at the wintering grounds, a reduction in time spent resting daily and a delayed start of breeding with lighter eggs and chicks and lower breeding success the following breeding season. Conversely, reduced reproductive effort resulted in more time resting and less time foraging during the winter, but a similar breeding phenology and success compared with control birds the following year, suggesting that ‘positive’ carry‐over effects may also occur but perhaps have a less long‐lasting impact than those incurred from increased reproductive effort.Our results shed light on how carry‐over effects can develop and modify an adult animal's behaviour year‐round and reveal how a complex interaction between current and future reproductive fitness, individual condition and external constraints can influence life‐history decisions.
Microbial diversity within the Trichodesmium holobiont
Authors: Rouco Mónica , Haley Sheean T. , Dyhrman Sonya T. 
Published: September 2016

SummaryNitrogen‐fixing cyanobacteria in the genus Trichodesmium play a critical role in the productivity of the tropical and subtropical oligotrophic oceans. The ecological success of these populations is likely associated with the diverse microbial interactions occurring within the Trichodesmium holobiont, especially between Trichodesmium and heterotrophic bacterial epibionts. Yet, the composition of the Trichodesmium holobiont and the processes governing microbial assemblage are not well documented. Here, we used high‐resolution 16S rDNA amplicon sequencing to examine the diversity of Trichodesmium and associated epibionts across different ocean regions and colony morphologies (puffs and rafts). Trichodesmium Clade I (i.e., T. thiebautii‐like) dominated the colonies in all ocean basins regardless of morphology, although the Trichodesmium community structure significantly varied between morphologies in some regions. On average, Alphaproteobacteria (i.e., Thalassobius), Gammaproteobacteria (i.e., Pseudoalteromonas), Sphingobacteria (i.e., Microscilla and Vibrio) and Flavobacteria dominated the epibiont communities, but community composition and structure significantly differed between regions. Epibionts from the two colony morphologies were taxonomically and functionally distinct in the North Atlantic and North Pacific. These findings suggest that the colony types might define two distinct niches and that epibiont assemblage might be driven in part by selective processes, where epibionts are selected according to their influence on colony metabolism.
Heterogeneous Treatment Effects? An Examination of Australian Non‐Government Primary Schools
Authors: Rodgers Joan , Neri Frank , Moran Ian 
Published: September 2016

AbstractOn average, students in Australian non‐government schools consistently outperform their counterparts in government schools on standardised tests of literacy and numeracy. However, when differences across school sectors in student characteristics are taken into account, this performance differential largely disappears. Nevertheless, non‐government schools may have heterogeneous effects; that is, they may benefit particular groups of students. This study investigates the extent of non‐government‐school advantage for specific primary‐school student groups using data from National Assessment Program–Literacy and Numeracy and the Longitudinal Study of Australian Children. We find no evidence that non‐government primary schools have a positive effect on academic outcomes of children, categorised by sex or socioeconomic status.
Taxation of Housing
Authors: Freebairn John 
Published: September 2016

AbstractThe effects of taxation on housing market outcomes, and implications for efficiency and distribution, are assessed. Current consumption, income and asset taxes are evaluated. Effects of the taxes on decisions to purchase own home versus rent for housing services and for investment of household savings in own home, other property or other options, such as bank deposits and superannuation, are considered. Replacing conveyance duty and the current narrow‐base land tax with a broad‐based land tax is advocated. A more radical reform proposal for a larger land tax and lower income tax‐mix change is assessed.
The Inexorable Rise in House Prices in Australia since 1970: Unique or Not?
Authors: Stapledon Nigel 
Published: September 2016

AbstractThe period since 1970 has seen a very significant rise in house prices and rents in real terms in Australia. The geographical variance in house prices in the United States over the same period provides an insight into the rising value attached to amenity and the impact of supply constraints in explaining the rise. Financial deregulation and low interest rates are the key factors that, after 1991, boosted prices but at the same time limited rent growth. These factors are a one‐off and not a guide to the future. The decline in home‐ownership rates requires a more nuanced debate.
The Costs of Fall‐Related Injuries among Older Adults: Annual Per‐Faller, Service Component, and Patient Out‐of‐Pocket Costs
Authors: Hoffman Geoffrey J. , Hays Ron D. , Shapiro Martin F. , Wallace Steven P. , Ettner Susan L. 
Published: September 2016

ObjectiveTo estimate expenditures for fall‐related injuries (FRIs) among older Medicare beneficiaries.Data SourcesThe 2007–2009 Medicare claims and 2008 Health and Retirement Study (HRS) data for 5,497 (228 FRI and 5,269 non‐FRI) beneficiaries.Study DesignFRIs were indicated by inpatient/outpatient ICD‐9 diagnostic codes for fractures, trauma, dislocations, and by e‐codes. A pre‐post comparison group design was used to estimate the differential change in pre‐post expenditures for the FRI relative to the non‐FRI cohort (FRI expenditures). Out‐of‐pocket (OOP) costs, service category total annual FRI‐related Medicare expenditures, expenditures related to the type of initial FRI treatment (inpatient, ED, outpatient), and the risk of persistently high expenditures (4th quartile for each post‐FRI quarter) were estimated.Principal FindingsEstimated FRI expenditures were $9,389 (95 percent CI: $5,969–$12,808). Inpatient, physician/outpatient, skilled nursing facility, and home health comprised 31, 18, 39, and 12 percent of the total. OOP costs were $1,363.0 (95 percent CI: $889‐$1,837). Expenditures for FRIs initially treated in inpatient/ED/outpatient settings were $21,424/$6,142/$8,622. The FRI cohort had a 64 percent increased risk of persistently high expenditures. Total Medicare expenditures were $13 billion (95 percent CI: $9–$18 billion).ConclusionsFRIs are associated with substantial, persistent Medicare expenditures. Cost‐effectiveness of multifactorial falls prevention programs should be assessed using these expenditure estimates.