bluuebunny/crossref_metadata_2025_split huggingface dataset:
PinAPL-Py: A comprehensive web-application for the analysis of CRISPR/Cas9 screens
Authors: Spahn Philipp N. , Bath Tyler , Weiss Ryan J. , Kim Jihoon , Esko Jeffrey D. , Lewis Nathan E. , Harismendy Olivier 
Published: June 2017

AbstractBackgroundLarge-scale genetic screens using CRISPR/Cas9 technology have emerged as a major tool for functional genomics. With its increased popularity, experimental biologists frequently acquire large sequencing datasets for which they often do not have an easy analysis option. While a few bioinformatic tools have been developed for this purpose, their utility is still hindered either due to limited functionality or the requirement of bioinformatic expertise.ResultsTo make sequencing data analysis of CRISPR/Cas9 screens more accessible to a wide range of scientists, we developed a Platform-independent Analysis of Pooled Screens using Python (PinAPL-Py), which is operated as an intuitive web-service. PinAPL-Py implements state-of-the-art tools and statistical models, assembled in a comprehensive workflow covering sequence quality control, automated sgRNA sequence extraction, alignment, sgRNA enrichment/depletion analysis and gene ranking. The workflow is set up to use a variety of popular sgRNA libraries as well as custom libraries that can be easily uploaded. Various analysis options are offered, suitable to analyze a large variety of CRISPR/Cas9 screening experiments. Analysis output includes ranked lists of sgRNAs and genes, and publication-ready plots.ConclusionsPinAPL-Py helps to advance genome-wide screening efforts by combining comprehensive functionality with user-friendly implementation. PinAPL-Py is freely accessible athttp://pinapl-py.ucsd.eduwith instructions, documentation and test datasets. The source code is available athttps://github.com/LewisLabUCSD/PinAPL-Py
TCGAbiolinksGUI: A graphical user interface to analyze GDC cancer molecular and clinical data
Authors: Silva Tiago C , Colaprico Antonio , Olsen Catharina , Bontempi Gianluca , Ceccarelli Michele , Berman Benjamin P , Noushmehr Houtan 
Published: June 2017

AbstractBackground:The GDC (Genomic Data Commons) data portal provides users with data from cancer genomics studies. Recently, we developed the R/Bioconductor TCGAbiolinks package, which allows users to search, download and prepare cancer genomics data for integrative data analysis. The use of this package requires users to have advanced knowledge of R thus limiting the number of users.Results:To overcome this obstacle and improve the accessibility of the package by a wider range of users, we developedTCGAbiolinksGUIthat uses shiny graphical user interface (GUI) available through the R/Bioconductor package.Conclusion:The TCGAbiolinksGUI package is freely available within the Bioconductor project athttp://bioconductor.org/packages/TCGAbiolinksGUI/. Links to the GitHub repository, a demo version of the tool, a docker image and PDF/video tutorials are available athttp://bit.do/TCGAbiolinksDocs.
Independent contributions of noradrenaline to behavioural flexibility and motivation
Authors: Jahn Caroline , Gilardeau Sophie , Varazzani Chiara , Blain Bastien , Sallet Jerome , Walton Mark , Bouret Sebastien 
Published: June 2017

AbstractAmong neuromodulatory systems, the noradrenergic system remains one of the least understood. Several theories have pointed out its implication in behavioural flexibility and more recently in motivation, with a strong role in effort processing. Here, we designed a sequential cost/benefit decision task to test the causal role of noradrenaline in these two functions. We manipulated noradrenaline using clonidine, an alpha-2 noradrenergic receptor agonist, which reduces central noradrenaline levels. Clonidine had two distinct effects: it decreased choice volatility (without affecting the cost/benefit trade off) and reduced force production. Because the effects were independent, they cannot be accounted for by a non-specific effect on arousal. Altogether, these results support the global implication of noradrenaline in facing challenging situations in two complementary ways: by modulating behavioural volatility, which would facilitate adaptation depending on the lability of the environment, and by modulating the mobilization of resources to face immediate challenges.
Highly parallel genome variant engineering with CRISPR/Cas9 in eukaryotic cells
Authors: Sadhu Meru J. , Bloom Joshua S. , Day Laura , Siegel Jake J. , Kosuri Sriram , Kruglyak Leonid 
Published: June 2017

AbstractDirect measurement of functional effects of DNA sequence variants throughout a genome is a major challenge. We developed a method that uses CRISPR/Cas9 to engineer many specific variants of interest in parallel in the budding yeastSaccharomyces cerevisiae, and to screen them for functional effects. We used the method to examine the functional consequences of premature termination codons (PTCs) at different locations within all annotated essential genes in yeast. We found that most PTCs were highly deleterious unless they occurred close to the C-terminal end and did not interrupt an annotated protein domain. Surprisingly, we discovered that some putatively essential genes are dispensable, while others have large dispensable regions. This approach can be used to profile the effects of large classes of variants in a high-throughput manner.
Competition in the savanna: models of species assemblages in Kruger National Park, South Africa
Authors: Ryan Sadie J. , Ladau Joshua 
Published: June 2017

AbstractWe examined hypotheses of spatial association arising from direct or indirect competitive interactions, using thirteen years of gridded mammal census data from Kruger National Park, South Africa. As interactions occur at different scales, we explored the data at 1, 5, 10, and 15 km2. We proposed four hypotheses structuring the mammal community: H1. direct competition between carnivores and herbivores; H2-4: indirect competition produced by each of three types of herbivore diet specialization: H2. ruminants and non-ruminants, H3. grazers and browsers, and H4. a four-way division of small and large grazers and browsers. We used the software CoOccur to implement a robus test for evidence of our hypotheses against null models of community assemblage. At 5, 10, and 15km2scales, the results supported a competition mechanism in the majority of years for hypotheses H1, H3, and H4, and facilitation in H2. At the finest spatial scale (1km2), we saw evidence for a mixture of competitive, neutral and facilitative process. These results suggest strong, large-scale effects of interspecific interactions on distributions of African megafauna, which may not operate at a more local (1km2) scale, underscoring the importance of scale and mechanism in the guild structure of communities.
A Negative Feedback Regulates The Flow Of Signal Through Akt/mTORC1/S6K1 Pathway
Authors: Dutta Poulami , Devaraj Vimalathithan , Bose Biplab 
Published: June 2017

AbstractSeveral growth factors, cytokines, hormones activate PI3K/Akt pathway. Akt is a key node in this pathway and activates different downstream paths. One such path is Akt/mTORC1/S6K1 that controls protein synthesis, cell survival, and proliferation. Here we show that a negative feedback controls activation of S6K1 through this pathway. Due to this negative feedback, a sustained phospho-Akt signal generates a transient pulse of phospho-S6K1. We have created a mathematical model for this circuit. Analysis of this model shows that the negative feedback acts as a filter and preferentially allows a signal, with sharp and faster rise of phospho-Akt, to induce pronounced activation of S6K1. It blocks an input with a fast oscillation of phospho-Akt to flow through this path. We show that this negative feedback leads to differential activation of S6K1 by Insulin and Insulin-like Growth Factor 1. Such differential effect may explain the difference in the mitogenic effect of these two molecules.
Robust Averaging Protects Decisions from Noise in Neural Computations
Authors: Li Vickie , Castañón Santiago Herce , Solomon Joshua A , Vandormael Hildward , Summerfield Christopher 
Published: June 2017

AbstractAn ideal observer will give equivalent weight to sources of information that are equally reliable. However, when averaging visual information, human observers tend to downweight or discount features that are relatively outlying or deviant (‘robust averaging’). Why humans adopt an integration policy that discards important decision information remains unknown. Here, observers were asked to judge the average tilt in a circular array of high-contrast gratings, relative to an orientation boundary defined by a central reference grating. Observers showed robust averaging of orientation, but the extent to which they did so was a positive predictor of their overall performance. Using computational simulations, we show that although robust averaging is suboptimal for a perfect integrator, it paradoxically enhances performance in the presence of “late” noise, i.e. which corrupts decisions during integration. In other words, robust decision strategies increase the brain’s resilience to noise arising in neural computations during decision-making.Author SummaryHumans often make decisions by averaging information from multiple sources. When all the sources are equally reliable, they should all have equivalent impact (or weight) on the decisions of an “ideal” observer, i.e. one with perfect memory. However, recent experiments have suggested that humans give unequal weight to sources that are deviant or unusual, a phenomenon called “robust averaging”. Here, we use computer simulations to try to understand why humans do this. Our simulations show that under the assumption that information processing is limited by a source of internal uncertainty that we call “late” noise, robust averaging actually leads to improved performance. Using behavioural testing, we replicate the finding of robust averaging in a cohort of healthy humans, and show that those participants that engage in robust averaging perform better on the task. This study thus provides new information about the limitations on human decision-making.
Integrating long-range connectivity information into de Bruijn graphs
Authors: Turner Isaac , Garimella Kiran V , Iqbal Zamin , McVean Gil 
Published: June 2017

AbstractMotivationThe de Bruijn graph is a simple and efficient data structure that is used in many areas of sequence analysis including genome assembly, read error correction and variant calling. The data structure has a single parameterk, is straightforward to implement and is tractable for large genomes with high sequencing depth. It also enables representation of multiple samples simultaneously to facilitate comparison. However, unlike the string graph, a de Bruijn graph does not retain long range information that is inherent in the read data. For this reason, applications that rely on de Bruijn graphs can produce sub-optimal results given their input.ResultsWe present a novel assembly graph data structure: theLinked de Bruijn Graph (LdBG). Constructed by adding annotations on top of a de Bruijn graph, it stores long range connectivity information through the graph. We show that with error-free data it is possible to losslessly store and recover sequence from a Linked de Bruijn graph. With assembly simulations we demonstrate that the LdBG data structure outperforms both the de Bruijn graph and the String Graph Assembler (SGA). Finally we apply the LdBG toKlebsiella pneumoniaeshort read data to make large (12 kbp) variant calls, which we validate using PacBio sequencing data, and to characterise the genomic context of drug-resistance genes.AvailabilityLinked de Bruijn Graphs and associated algorithms are implemented as part of McCortex, available under the MIT license athttps://github.com/mcvean/mccortex.Contactturner.isaac@gmail.com.
A DNA Contact Map for the MouseRunx1Gene Identifies Novel Hematopoietic Enhancers
Authors: Marsman Judith , Thomas Amarni , Osato Motomi , O’Sullivan Justin M. , Horsfield Julia A. 
Published: June 2017

AbstractThe transcription factor Runx1 is essential for definitive hematopoiesis, and theRUNX1gene is frequently translocated or mutated in leukemia.Runx1is transcribed from two promoters, P1 and P2, to give rise to different protein isoforms. Although the expression of Runx1 must be tightly regulated for normal blood development, the mechanisms that regulateRunx1isoform expression during hematopoiesis remain poorly understood. Gene regulatory elements located in non-coding DNA are likely to be important forRunx1transcription. Here we use circular chromosome conformation capture sequencing to identify DNA interactions with the P1 and P2 promoters ofRunx1, and the previously identified +24 enhancer, in the mouse multipotent hematopoietic progenitor cell line HPC-7. The active promoter, P1, interacts with nine non-coding regions that are occupied by transcription factors within a 1 Mb topologically associated domain. Eight of nine regions function as blood-specific enhancers in zebrafish. Interestingly, the +24 enhancer interacted with multiple distant regions on chromosome 16, indicating it may regulate the expression of additional genes. TheRunx1DNA contact map identifies connections with multiple novel hematopoietic enhancers that are likely to be involved in regulatingRunx1expression in hematopoietic progenitor cells.
Metabolomics and biochemical approaches link salicylic acid biosynthesis to cyanogenesis in peach plants
Authors: Pedro Diaz-Vivancos , Agustina Bernal-Vicente , Daniel Cantabella , Cesar Petri , Antonio Hernández José 
Published: June 2017

HighlightMandelonitrile, and hence cyanogenic glycosides turnover, is involved in salicylic acid (SA) biosynthesis in peach plants under control and stress conditions. A third pathway for SA synthesis in peach is proposed.AbstractDespite the long-established importance of salicylic acid (SA) in plant stress responses and other biological processes, its biosynthetic pathway has not been fully characterized. The proposed SA synthesis originates from chorismate by two distinct pathways: isochorismate and penhylalanine (Phe) ammonia-lyase (PAL) pathways. Cyanogenesis is the process related to the release of hydrogen cyanide from endogenous cyanogenic glycosides (CNglcs), and it has been linked to plant plasticity improvement. To date, however, no relationship has been suggested between both pathways. In this work, by metabolomics and biochemical approaches (including [13C]-labelled compounds), we provide evidences showing that CNglcs turnover is involved, at least in part, in SA biosynthesis in peach plants under control and stress conditions.The main CNglcs in peach are prunasin and amygdalin, with mandelonitrile (MD), synthesized from Phe, controlling their turnover. In peach plants MD is at the hub of the suggested new SA biosynthetic pathway and CNglcs turnover, regulating both the amygdalin and SA biosynthesis. MD-treated peach plants displayed increased SA levels via benzoic acid (SA precursor). In addition, MD also provides partial protection againstPlum pox virusinfection in peach seedlings. Thus, we proposed a third pathway, alternative to the PAL pathway, for SA synthesis in peach plants.
WebMeV: a Cloud Platform for Analyzing and Visualizing Cancer Genomic Data
Authors: Wang Yaoyu E. , Kuznetsov Lev , Partensky Antony , Farid Jalil , Quackenbush John 
Published: June 2017

AbstractAlthough large, complex genomic data sets are increasingly easy to generate, and the number of publicly available data sets in cancer and other diseases is rapidly growing, the lack of intuitive, easy to use analysis tools has remained a barrier to the effective use of such data. WebMeV (https://mev.tm4.org) is an open-source, web-based tool that gives users access to sophisticated tools for analysis of RNA-Seq and other data in an interface designed to democratize data access. WebMeV combines cloud-based technologies with a simple user interface to allow users to access large public data sets such as that from The Cancer Genome Atlas (TCGA) or to upload their own. The interface allows users to visualize data and to apply advanced data mining analysis methods to explore the data and draw biologically meaningful conclusions. We provide an overview of WebMeV and demonstrate two simple use cases that illustrate the value of putting data analysis in the hands of those looking to explore the underlying biology of the systems being studied.
Polarization effects and the calibration of a donut beam axial optical tweezers for single-molecule force spectroscopy
Authors: Pollari Russell , Milstein Joshua 
Published: June 2017

ABSTRACTAdvances in light shaping techniques are leading to new tools for optical trapping and micromanipulation. For example, optical tweezers made from Laguerre-Gaussian or donut beams display an increased axial trap strength and can impart angular momentum to rotate a specimen. However, their application to precision, biophysical measurements remains limited as their are a number of challenges to applying this tool to optical force spectroscopy. One notable complication, not present when trapping with a Gaussian beam, is that the polarization of the trap light can significantly affect the tweezers’ strength as well as the precise location of the trap. In this article, we provide a practical implementation of a donut beam optical tweezers for applying axial forces. We show how to precisely calibrate the height of the optical trap above the coverslip surface while accounting for focal shifts in the trap position that arise due to radiation pressure, mismatches in the index of refraction, and polarization induced intensity variations.
eGARD: Extracting associations between genomic anomalies and drug responses from text
Authors: Mahmood A. S. M. Ashique , Rao Shruti , McGarvey Peter , Wu Cathy , Madhavan Subha , Vijay-Shanker K. 
Published: June 2017

AbstractTumor molecular profiling plays an integral role in identifying genomic anomalies which may help in personalizing cancer treatments, improving patient outcomes and minimizing risks associated with different therapies. However, critical information regarding the evidence of clinical utility of such anomalies is largely buried in biomedical literature. It is becoming prohibitive for biocurators, clinical researchers and oncologists to keep up with the rapidly growing volume and breadth of information, especially those that describe therapeutic implications of biomarkers and therefore relevant for treatment selection. In an effort to improve and speed up the process of manually reviewing and extracting relevant information from literature, we have developed a natural language processing (NLP)-based text mining (TM) system called eGARD (extracting Genomic Anomalies association with Response to Drugs). This system relies on the syntactic nature of sentences coupled with various textual features to extract relations between genomic anomalies and drug response from MEDLINE abstracts. Our system achieved high precision, recall and F-measure of up to 0.95, 0.86 and 0.90, respectively, on annotated evaluation datasets created in-house and obtained externally from PharmGKB. Additionally, the system extracted information that helps determine the confidence level of extraction to support prioritization of curation. Such a system will enable clinical researchers to explore the use of published markers to stratify patients upfront for ‘best-fit’ therapies and readily generate hypotheses for new clinical trials.
Saccharomyces cerevisiaeas a Platform for Assessing Sphingolipid Lipid Kinase Inhibitors
Authors: Kharel Yugesh , Agah Sayeh , Huang Tao , Mendelson Anna J. , Eletu Oluwafunmilayo T. , Barkey-Bircann Peter , Gesualdi James , Smith Jeffrey S. , Santos Webster L. , Lynch Kevin R. 
Published: June 2017

AbstractSuccessful medicinal chemistry campaigns to discover and optimize sphingosine kinase inhibitors require a robust assay for screening chemical libraries and for determining rank order potencies. Existing assays for these enzymes are laborious, expensive and/or low throughput. The toxicity of excessive levels of phosphorylated sphingoid bases for the budding yeast,Saccharomyces cerevisiae, affords an assay wherein inhibitors added to the culture media rescue growth in a dose-dependent fashion. Herein, we describe our adaptation of a simple, inexpensive, and high throughput assay for assessing inhibitors of sphingosine kinase types 1 and 2 as well as ceramide kinase and for testing enzymatic activity of sphingosine kinase type 2 mutants. The assay was validated using recombinant enzymes and generally agrees with rank order of potencies of existing inhibitors.
Investigation of turbulent flow through microchannels consisting of different micropost arrangements
Authors: Kharati-Koopaee Masoud , Rezaee Mahsa 
Published: June 2017

Purpose
The purpose of the current research is to study the turbulent flow through microchannels having a micropost in aligned and staggered arrangements.

Design/methodology/approach
Numerical calculations are performed on the basis of the finite volume approach, which is based on the SIMPLEC algorithm. In this work, the slip velocity, flow velocity distribution and friction factor for the two micropost patterns are examined at friction Reynolds numbers of Reτ = 395 and 590, relative module widths of Wm = 0.1 and 1 and cavity fraction range of Fc = 0.1 to 0.9.

Findings
Results reveal that for the two micropost patterns, as the friction Reynolds number, relative module width or cavity fraction increases, the slip velocity increases and friction factor decreases. It is found that the aligned micropost configuration leads to higher slip velocity and lower friction factor. Numerical findings indicate that the existence of the continuous cavity surface along the flow direction could be a significant criterion to realize if the velocity distribution deviates from that of the smooth channel. It is also shown that the turbulent flows are capable of producing more drag reduction than the laminar ones.

Originality/value
Previous studies have shown that microchannels consisting of a micropost pattern in aligned and staggered arrangements could be viewed as a promising alternative in the microscale flows for the heat removal purposes. Therefore, understanding the fluid flow through microchannels consisting of these configurations (which is a prerequisite to better understand thermal performance of such microchannels) is a significant issue, which is the subject of the present work.