bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subtype-specific and co-occurring genetic alterations in B-cell non-Hodgkin lymphoma
Authors: Ma Man Chun John , Tadros Saber , Bouska Alyssa , Heavican Tayla , Yang Haopeng , Deng Qing , Moore Dalia , Akhter Ariz , Hartert Keenan , Jain Neeraj , Showell Jordan , Ghosh Sreejoyee , Street Lesley , Davidson Marta , Carey Christopher , Tobin Joshua , Perumal Deepak , Vose Julie M. , Lunning Matthew A. , Sohani Aliyah R. , Chen Benjamin J. , Buckley Shannon , Nastoupil Loretta J. , Davis R. Eric , Westin Jason R. , Fowler Nathan H. , Parekh Samir , Gandhi Maher , Neelapu Sattva , Stewart Douglas , Bhalla Kapil , Iqbal Javeed , Greiner Timothy , Rodig Scott J. , Mansoor Adnan , Green Michael R. 
Published: June 2019

ABSTRACTB-cell non-Hodgkin’s lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL such as diffuse large B-cell lymphoma (DLBCL) have been comprehensively interrogated at the genomic level. But rarer subtypes such as mantle cell lymphoma (MCL) remain sparsely characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth; including DLBCL, MCL, follicular lymphoma (FL), and Burkitt lymphoma (BL). We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumor from each subtype, including the frequent genetic deregulation of the ubiquitin proteasome system (UPS). In addition, we identified subtype-specific patterns of genetic alterations, including clusters of co-occurring mutations and DNA copy number alterations. The cumulative burden of mutations within a single cluster were more discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic cooperation that contribute to disease etiology. We therefore provide the first cross-sectional analysis of mutations and DNA copy number alterations across major B-NHL subtypes and a framework of co-occurring genetic alterations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis.
Towards a gold standard for benchmarking gene set enrichment analysis
Authors: Geistlinger Ludwig , Csaba Gergely , Santarelli Mara , Ramos Marcel , Schiffer Lucas , Law Charity , Turaga Nitesh , Davis Sean , Carey Vincent , Morgan Martin , Zimmer Ralf , Waldron Levi 
Published: June 2019

AbstractBackgroundAlthough gene set enrichment analysis has become an integral part of high-throughput gene expression data analysis, the assessment of enrichment methods remains rudimentary and ad hoc. In the absence of suitable gold standards, evaluations are commonly restricted to selected data sets and biological reasoning on the relevance of resulting enriched gene sets. However, this is typically incomplete and biased towards the goals of individual investigations.ResultsWe present a general framework for standardized and structured benchmarking of enrichment methods based on defined criteria for applicability, gene set prioritization, and detection of relevant processes. This framework incorporates a curated compendium of 75 expression data sets investigating 42 different human diseases. The compendium features microarray and RNA-seq measurements, and each dataset is associated with a precompiled GO/KEGG relevance ranking for the corresponding disease under investigation. We perform a comprehensive assessment of 10 major enrichment methods on the benchmark compendium, identifying significant differences in (i) runtime and applicability to RNA-seq data, (ii) fraction of enriched gene sets depending on the type of null hypothesis tested, and (iii) recovery of thea prioridefined relevance rankings. Based on these findings, we make practical recommendations on (i) how methods originally developed for microarray data can efficiently be applied to RNA-seq data, (ii) how to interpret results depending on the type of gene set test conducted, and (iii) which methods are best suited to effectively prioritize gene sets with high relevance for the phenotype investigated.ConclusionWe carried out a systematic assessment of existing enrichment methods, and identified best performing methods, but also general shortcomings in how gene set analysis is currently conducted. We provide a directly executable benchmark system for straightforward assessment of additional enrichment methods.Availabilityhttp://bioconductor.org/packages/GSEABenchmarkeR
NONU-1 encodes a conserved endonuclease required for mRNA translation surveillance
Authors: Glover Marissa L. , Burroughs A. Max. , Egelhofer Thea A. , Pule Makena N. , Aravind L. , Arribere Joshua A. 
Published: June 2019

ABSTRACTCellular translation surveillance rescues ribosomes that stall on problematic mRNAs. During translation surveillance, endonucleolytic cleavage of the problematic mRNA is a critical step in rescuing stalled ribosomes. However, the nuclease(s) responsible remain unknown. Here we identify NONU-1 as a novel endoribonuclease required for translation surveillance pathways including No-Go and Nonstop mRNA Decay. We show that: (1) NONU-1 reduces Nonstop and No-Go mRNA levels; (2) NONU-1 contains an Smr RNase domain required for mRNA decay and with properties similar to the unknown endonuclease; and (3) the domain architecture and catalytic residues of NONU-1 are conserved throughout metazoans and eukaryotes, respectively. We extend our results inC. elegansto homologous factors inS. cerevisiae, showing conservation of function of the NONU-1 protein across billions of years of evolution. Our work establishes the identity of a previously unknown factor critical to translation surveillance and will inform mechanistic studies at the intersection of translation and mRNA decay.
Infect While the Iron is Scarce: Nutrient Explicit Phage-Bacteria Games
Authors: Muratore Daniel , Weitz Joshua S. 
Published: June 2019

AbstractMarine microbial primary production is influenced by the availability and uptake of essential nutrients, including iron. Although marine microbes have evolved mechanisms to scavenge sub-nanomolar concentrations of iron, recent observations suggest that viruses may co-opt these very same mechanisms to facilitate infection. The “Ferrojan Horse Hypothesis” proposes that viruses incorporate iron atoms into their tail fiber proteins to adsorb to target host receptors. Here, we propose an evolutionary game theoretic approach to consider the joint strategies of hosts and viruses in environments with limited nutrients (like iron). We analyze the bimatrix game and find that evolutionarily stable strategies depend on the stability and quality of nutrient conditions. For example, in highly stable iron conditions, virus pressure does not change host uptake strategies. However, when iron levels are dynamic, virus pressure can lead to fluctuations in the extent to which hosts invest in metabolic machinery that increases both iron uptake and susceptibility to viral infection. Altogether, this evolutionary game model provides further evidence that viral infection and nutrient dynamics jointly shape the fate of microbial populations.
Manipulation of Seedling Traits with Pulsed Light in Closed Controlled Environments
Authors: Song Shiwei , Kusuma Paul , Carvalho Sofia D. , Li Yan , Folta Kevin M. 
Published: June 2019

AbstractThere is substantial interest in growing crops in closed controlled environments, yet the energy requirements are high. Energy is required to produce light, but also to remove the heat generated when producing light. The goal of the current work examines a possible approach to decrease the energy requirement. The effect of pulsed light treatments was examined by monitoring seedling traits during early photomorphogenic development. Daily light integral remained unchanged between treatments, but the frequency of the pulses was varied. Developmental traits (such as inhibition of hypocotyl elongation rate) were most conspicuous during a normal photoperiod, as in twelve hours light, twelve hours darkness. Consistent with historical reports, when treatments were delivered in shorter durations (e.g. 1 hour on/off) photomorphogenic development was hindered, with the same daily light integral. However, at even shorter light intervals (e.g. seconds) seedlings developed as if they were provided full 12 h treatments. Extension of the dark period following a 5 s pulse was tested to determine the effect on seedling traits. The results showed that the dark period could be extended to at least 10 s without affecting seedling development, and extension to 20 s only had slight effects on seedling traits. The mechanism of the phenomenon was examined in Arabidopsis photosensory mutants, with substantial contributions from the phyA and cry1 pathways. The results suggest that pulsed light with extended dark periods can decrease energy input by at least 30% to >50% without affecting visible seedling traits. These pilot experiments in seedlings demonstrate that implementation of short-interval, pulsed-light strategies may lower energy requirements for growing crops in artificially illuminated environments.
Attraction of Triatoma infestans (Klug) to adhesive yeast-baited trap under laboratory conditions
Authors: Cardozo Miriam , Fiad Federico G. , Crocco Liliana B. , Gorla David E. 
Published: June 2019

AbstractExisting methods to detect domestic triatomines have low sensitivity. As early house infestation detection is epidemiologically important, the exploration of better methods is required. Hence, we measured the attractiveness of a yeast-baited trap to adults and nymphs of Triatoma infestans, under laboratory conditions.The assays were conducted in an experimental arena, with an experimental and a control traps placed at opposite sides and one refuge in the center area. Insects where released and the number of triatomines in the yeast and control traps were counted, after 3, 6 and 24 hours of the beginning of the experiment. We use generalized linear models within a multimodel inference approach to model the number of insects in the trap, using insect age classes, time after assay initiation and date of the experiment as predictors.Our results show that the attraction to CO2 depends upon the life stage of the insects. During the 24 hours of experiment a constant number of adults were attracted to the yeast trap, while nymphs show attraction only up to the first three hours after the initiation of CO2 liberation. Undoubtedly, the orientation response to chemical cues deserves further studies to be fully understood.
Gene expression analysis of Cyanophora paradoxa reveals conserved abiotic stress responses between basal algae and flowering plants
Authors: Ferrari Camilla , Mutwil Marek 
Published: June 2019

SummaryThe glaucophyte Cyanophora paradoxa represents the most basal member of the Archaeplastida kingdom, however the function and expression of most of its genes are unknown. This information is needed to uncover how functional gene modules, i.e. groups of genes performing a given function, evolved in the plant kingdom.We have generated a gene expression atlas capturing responses of Cyanophora to various abiotic stresses. This data was included in the CoNekT-Plants database, enabling comparative transcriptomic analyses across two algae and six land plants.We demonstrate how the database can be used to study gene expression, co-expression networks and gene function in Cyanophora, and how conserved transcriptional programs can be identified. We identified gene modules involved in phycobilisome biosynthesis, response to high light and cell division. While we observed no correlation between the number of differentially expressed genes and the impact on growth of Cyanophora, we found that the response to stress involves a conserved, kingdom-wide transcriptional reprogramming, which is activated upon most stresses in algae and land plants.The Cyanophora stress gene expression atlas and the tools found in https://conekt.plant.tools/ database provide a useful resource to reveal functionally related genes and stress responses in the plant kingdom.
Aneuploidy Spectrum Analysis as a Primer for Copy Number Profiling of Cancer Cells
Authors: Samir Khalil Ahmed Ibrahim , Chattopadhyay Anupam , Sanyal Amartya 
Published: June 2019

AbstractMotivationHyperploidy and segmental aneuploidy are hallmarks of cancer cells due to chromosome segregation errors and genomic instability. In such situations, accurate aneuploidy profiling of cancer data is critical for calibration of copy number (CN)-detection tools. Additionally, cancer cell populations suffer from different levels of clonal heterogeneity and aneuploidy alterations over time. The degree of heterogeneity adversely affects the segregation of the depth of coverage (DOC) signal into integral CN states. This, in turn, strongly influences the reliability of this data for ploidy profiling and copy number variation (CNV) analysis.ResultsWe developed AStra framework for aneuploidy profiling of cancer data and assessing their suitability for copy number analysis without any prior knowledge of the input sequencing data. AStra estimates the best-fit aneuploidy profile as the spectrum with most genomic segments around integral CN states. We employ this spectrum to extract the CN-associated features such as the homogeneity score (HS), whole-genome ploidy level, and CN correction factor. The HS measures the percentage of genomic regions around CN states. It is used as a reliability assessment of sequencing data for downstream aneuploidy profiling and CNV analysis. We evaluated the accuracy of AStra using 31 low-coverage datasets from 20 cancer cell lines. AStra successfully identified the aneuploidy spectrum of complex cell lines with HS greater than 75%. Benchmarking against nQuire tool showed that AStra is superior in detecting the ploidy level using both low- and high-coverage data. Furthermore, AStra accurately estimated the ploidy of 26/27 strains of MCF7 (hyperploid) cell line which exhibit varied levels of aneuploidy spectrum and heterogeneity. Remarkably, we found that HS is strongly correlated with the doubling time of these strains.Availability and implementationAStra is an open source software implemented in Python and is available at https://github.com/AISKhalil/AStra
Bayesian inference of ancestral host-parasite interactions under a phylogenetic model of host repertoire evolution
Authors: Braga Mariana P , Landis Michael , Nylin Sören , Janz Niklas , Ronquist Fredrik 
Published: June 2019

AbstractIntimate ecological interactions, such as those between parasites and their hosts, may persist over long time spans, coupling the evolutionary histories of the lineages involved. Most methods that reconstruct the coevolutionary history of such associations make the simplifying assumption that parasites have a single host. Many methods also focus on congruence between host and parasite phylogenies, using cospeciation as the null model. However, there is an increasing body of evidence suggesting that the host ranges of parasites are more complex: that host ranges often include more than one host and evolve via gains and losses of hosts rather than through cospeciation alone. Here, we develop a Bayesian approach for inferring coevolutionary history based on a model accommodating these complexities. Specifically, a parasite is assumed to have a host repertoire, which includes both potential hosts and one or more actual hosts. Over time, potential hosts can be added or lost, and potential hosts can develop into actual hosts or vice versa. Thus, host colonization is modeled as a two-step process, which may potentially be influenced by host relatedness or host traits. We first explore the statistical behavior of our model by simulating evolution of host-parasite interactions under a range of parameters. We then use our approach, implemented in the program RevBayes, to infer the coevolutionary history between 34 Nymphalini butterfly species and 25 angiosperm families.
Terasaki Spiral Ramps and Intracellular Diffusion
Authors: Huber Greg , Wilkinson Michael 
Published: June 2019

AbstractThe sheet-like endoplasmic reticulum (ER) of eukaryotic cells has been found to be riddled with spiral dislocations, known as ‘Terasaki ramps’, in the vicinity of which the doubled bilayer membranes which make up ER sheets can be approximately modeled by helicoids. Here we analyze diffusion on a surface with locally helicoidal topological dislocations, and use the results to argue that the Terasaki ramps facilitate a highly efficient transport of water-soluble molecules within the lumen of the endoplasmic reticulum.
Metaecosystem dynamics drive community composition in experimental multilayered spatial networks
Authors: Harvey Eric , Gounand Isabelle , Fronhofer Emanuel A. , Altermatt Florian 
Published: June 2019

AbstractCross-ecosystem subsidies are studied with a focus on resource exchange at local ecosystem boundaries. This perspective ignores regional dynamics that can emerge via constraints imposed by the landscape, potentially leading to spatially-dependent effects of subsidies and spatial feedbacks. Using miniaturized landscape analogues of river dendritic and terrestrial lattice spatial networks, we manipulated and studied resource exchange between the two whole networks. We found that community composition in dendritic networks depended on the resource pulse from the lattice network, with the strength of this effect declining in larger downstream patches. In turn, this spatially-dependent effect imposed constraints on the lattice network with populations in that network reaching higher densities when connected to more central patches in the dendritic network. Consequently, localized cross-ecosystem fluxes, and their respective effects on recipient ecosystems, must be studied in a perspective taking into account the explicit spatial configuration of the landscape.Statement of authorshipEH, IG, EAF and FA designed the research; EH conducted the lab experiment with support from IG, EAF and FA, processed the experimental data with methodological developments from IG, and carried out the analysis of experimental data; all authors participated in results interpretation; EH wrote the first draft of the manuscript; All authors significantly contributed to further manuscript revisions.
Prolonged ovarian storage of matureDrosophilaoocytes dramatically increases meiotic spindle instability
Authors: Greenblatt Ethan J. , Obniski Rebecca , Mical Claire , Spradling Allan C. 
Published: June 2019

SummaryMore than 95% of fertilizedDrosophilaoocytes from outbred stocks develop fully regardless of maternal age, in contrast to human oocytes, which frequently generate non-viable aneuploid embryos. SinceDrosophilaoocytes are normally stored only briefly prior to ovulation, unlike their human counterparts, we investigated the effects of storage on oocyte quality. Using a novel system to acquire oocytes held for known periods, we analyzed by ribosome profiling how translation and cellular function change over time. Oocyte developmental capacity decays in a precise temperature-dependent manner over 1-4 weeks, due to a progressive inability to complete meiosis. Meiotic metaphase genes, theFmr1translational regulator, and the small heat shock protein chaperonesHsp26andHsp27are preferentially translated during storage, and oocytes lackingHsp26andHsp27age prematurely. However translation falls generally 2.3-fold with age despite constant mRNA levels, and this inability to maintain translational equilibrium correlates with oocyte functional decline. These findings show that meiotic chromosome segregation inDrosophilaoocytes is uniquely sensitive to prolonged quiescence, and suggest that the extended storage of mature human oocytes contributes to their chromosome instability. If so, then these problems may be more amenable to intervention than previously supposed.
Concurrent Genome and Epigenome Editing by CRISPR-Mediated Sequence Replacement
Authors: Alexander Jes , Findlay Gregory M. , Kircher Martin , Shendure Jay 
Published: June 2019

AbstractRecent advances in genome editing have facilitated the direct manipulation of not only the genome, but also the epigenome. Genome editing is typically performed by introducing a single CRISPR/Cas9-mediated double stranded break (DSB), followed by NHEJ or HDR mediated repair. Epigenome editing, and in particular methylation of CpG dinucleotides, can be performed using catalytically inactive Cas9 (dCas) fused to a methyltransferase domain. However, for investigations of the role of methylation in gene silencing, studies based on dCas9-methyltransferase have limited resolution and are potentially confounded by the effects of binding of the fusion protein. As an alternative strategy for epigenome editing, we tested CRISPR/Cas9 dual cutting of the genome in the presence of in vitro methylated exogenous DNA, i.e. to drive replacement of the DNA sequence intervening the dual cuts via NHEJ. In a proof-of-concept at the HPRT1 promoter, successful replacement events with heavily methylated alleles of a CpG island resulted in functional silencing of the HPRT1 gene. Although still limited in efficiency, our study demonstrates concurrent epigenome and genome editing in a single event, and opens the door to investigations of the functional consequences of methylation patterns at single CpG dinucleotide resolution. Our results furthermore support the conclusion that promoter methylation is sufficient to functionally silence gene expression.
Differential Allele-Specific Expression Uncovers Breast Cancer Genes Dysregulated By Cis Noncoding Mutations
Authors: Przytycki Pawel F , Singh Mona 
Published: June 2019

SummaryIdentifying cancer-relevant mutations in noncoding regions is extremely challenging due to the large numbers of such mutations, their low levels of recurrence, and the general difficulty in interpreting their impact. To uncover genes that are dysregulated due to somatic mutations in cis, we build upon the concept of differential allele-specific expression (ASE) and introduce methods to identify genes within an individual’s cancer whose ASE differs from what is found in matched normal tissue. When applied to breast cancer tumor samples, our methods readily detect the known allele-specific effects of copy number variation and nonsense-mediated decay. Further, genes that are found to recurrently exhibit differential ASE across samples are cancer relevant. Genes with cis mutations are enriched for differential ASE, and we find 147 potentially functional noncoding mutations cis to genes that exhibit significant differential ASE. Overall, our results suggest that differential ASE is a promising means for discovering gene dysregulation within an individual due to cis noncoding mutations.