178 research outputs found

    Discovery and Expansion of Gene Modules by Seeking Isolated Groups in a Random Graph Process

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    BACKGROUND: A central problem in systems biology research is the identification and extension of biological modules-groups of genes or proteins participating in a common cellular process or physical complex. As a result, there is a persistent need for practical, principled methods to infer the modular organization of genes from genome-scale data. RESULTS: We introduce a novel approach for the identification of modules based on the persistence of isolated gene groups within an evolving graph process. First, the underlying genomic data is summarized in the form of ranked gene-gene relationships, thereby accommodating studies that quantify the relevant biological relationship directly or indirectly. Then, the observed gene-gene relationship ranks are viewed as the outcome of a random graph process and candidate modules are given by the identifiable subgraphs that arise during this process. An isolation index is computed for each module, which quantifies the statistical significance of its survival time. CONCLUSIONS: The Miso (module isolation) method predicts gene modules from genomic data and the associated isolation index provides a module-specific measure of confidence. Improving on existing alternative, such as graph clustering and the global pruning of dendrograms, this index offers two intuitively appealing features: (1) the score is module-specific; and (2) different choices of threshold correlate logically with the resulting performance, i.e. a stringent cutoff yields high quality predictions, but low sensitivity. Through the analysis of yeast phenotype data, the Miso method is shown to outperform existing alternatives, in terms of the specificity and sensitivity of its predictions

    ICC-CLASS: isotopically-coded cleavable crosslinking analysis software suite

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    <p>Abstract</p> <p>Background</p> <p>Successful application of crosslinking combined with mass spectrometry for studying proteins and protein complexes requires specifically-designed crosslinking reagents, experimental techniques, and data analysis software. Using isotopically-coded ("heavy and light") versions of the crosslinker and cleavable crosslinking reagents is analytically advantageous for mass spectrometric applications and provides a "handle" that can be used to distinguish crosslinked peptides of different types, and to increase the confidence of the identification of the crosslinks.</p> <p>Results</p> <p>Here, we describe a program suite designed for the analysis of mass spectrometric data obtained with isotopically-coded <it>cleavable </it>crosslinkers. The suite contains three programs called: DX, DXDX, and DXMSMS. DX searches the mass spectra for the presence of ion signal doublets resulting from the light and heavy isotopic forms of the isotopically-coded crosslinking reagent used. DXDX searches for possible mass matches between cleaved and uncleaved isotopically-coded crosslinks based on the established chemistry of the cleavage reaction for a given crosslinking reagent. DXMSMS assigns the crosslinks to the known protein sequences, based on the isotopically-coded and un-coded MS/MS fragmentation data of uncleaved and cleaved peptide crosslinks.</p> <p>Conclusion</p> <p>The combination of these three programs, which are tailored to the analytical features of the specific isotopically-coded cleavable crosslinking reagents used, represents a powerful software tool for automated high-accuracy peptide crosslink identification. See: <url>http://www.creativemolecules.com/CM_Software.htm</url></p

    Asteroids' physical models from combined dense and sparse photometry and scaling of the YORP effect by the observed obliquity distribution

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    The larger number of models of asteroid shapes and their rotational states derived by the lightcurve inversion give us better insight into both the nature of individual objects and the whole asteroid population. With a larger statistical sample we can study the physical properties of asteroid populations, such as main-belt asteroids or individual asteroid families, in more detail. Shape models can also be used in combination with other types of observational data (IR, adaptive optics images, stellar occultations), e.g., to determine sizes and thermal properties. We use all available photometric data of asteroids to derive their physical models by the lightcurve inversion method and compare the observed pole latitude distributions of all asteroids with known convex shape models with the simulated pole latitude distributions. We used classical dense photometric lightcurves from several sources and sparse-in-time photometry from the U.S. Naval Observatory in Flagstaff, Catalina Sky Survey, and La Palma surveys (IAU codes 689, 703, 950) in the lightcurve inversion method to determine asteroid convex models and their rotational states. We also extended a simple dynamical model for the spin evolution of asteroids used in our previous paper. We present 119 new asteroid models derived from combined dense and sparse-in-time photometry. We discuss the reliability of asteroid shape models derived only from Catalina Sky Survey data (IAU code 703) and present 20 such models. By using different values for a scaling parameter cYORP (corresponds to the magnitude of the YORP momentum) in the dynamical model for the spin evolution and by comparing synthetics and observed pole-latitude distributions, we were able to constrain the typical values of the cYORP parameter as between 0.05 and 0.6.Comment: Accepted for publication in A&A, January 15, 201

    Detection of Crosslinks within and between Proteins by LC-MALDI-TOFTOF and the Software FINDX to Reduce the MSMS-Data to Acquire for Validation

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    Lysine-specific chemical crosslinking in combination with mass spectrometry is emerging as a tool for the structural characterization of protein complexes and protein-protein interactions. After tryptic digestion of crosslinked proteins there are thousands of peptides amenable to MSMS, of which only very few are crosslinked peptides of interest. Here we describe how the advantage offered by off-line LC-MALDI-TOF/TOF mass spectrometry is exploited in a two-step workflow to focus the MSMS-acquisition on crosslinks mainly. In a first step, MS-data are acquired and all the peak list files from the LC-separated fractions are merged by the FINDX software and screened for presence of crosslinks which are recognized as isotope-labeled doublet peaks. Information on the isotope doublet peak mass and intensity can be used as search constraints to reduce the number of false positives that match randomly to the observed peak masses. Based on the MS-data a precursor ion inclusion list is generated and used in a second step, where a restricted number of MSMS-spectra are acquired for crosslink validation. The decoupling of MS and MSMS and the peptide sorting with FINDX based on MS-data has the advantage that MSMS can be restricted to and focused on crosslinks of Type 2, which are of highest biological interest but often lowest in abundance. The LC-MALDI TOF/TOF workflow here described is applicable to protein multisubunit complexes and using 14N/15N mixed isotope strategy for the detection of inter-protein crosslinks within protein oligomers

    Ready for O4 II: GRANDMA Observations of Swift GRBs during eight-weeks of Spring 2022

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    We present a campaign designed to train the GRANDMA network and its infrastructure to follow up on transient alerts and detect their early afterglows. In preparation for O4 II campaign, we focused on GRB alerts as they are expected to be an electromagnetic counterpart of gravitational-wave events. Our goal was to improve our response to the alerts and start prompt observations as soon as possible to better prepare the GRANDMA network for the fourth observational run of LIGO-Virgo-Kagra (which started at the end of May 2023), and future missions such as SM. To receive, manage and send out observational plans to our partner telescopes we set up dedicated infrastructure and a rota of follow-up adcates were organized to guarantee round-the-clock assistance to our telescope teams. To ensure a great number of observations, we focused on Swift GRBs whose localization errors were generally smaller than the GRANDMA telescopes' field of view. This allowed us to bypass the transient identification process and focus on the reaction time and efficiency of the network. During 'Ready for O4 II', 11 Swift/INTEGRAL GRB triggers were selected, nine fields had been observed, and three afterglows were detected (GRB 220403B, GRB 220427A, GRB 220514A), with 17 GRANDMA telescopes and 17 amateur astronomers from the citizen science project Kilonova-Catcher. Here we highlight the GRB 220427A analysis where our long-term follow-up of the host galaxy allowed us to obtain a photometric redshift of z=0.82±0.09z=0.82\pm0.09, its lightcurve elution, fit the decay slope of the afterglows, and study the properties of the host galaxy

    GRANDMA and HXMT Observations of GRB 221009A -- the Standard-Luminosity Afterglow of a Hyper-Luminous Gamma-Ray Burst

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    GRB 221009A is the brightest Gamma-Ray Burst (GRB) detected in more than 50 years of study. In this paper, we present observations in the X-ray and optical domains after the GRB obtained by the GRANDMA Collaboration (which includes observations from more than 30 professional and amateur telescopes) and the Insight-HXMT Collaboration. We study the optical afterglow with empirical fitting from GRANDMA+HXMT data, augmented with data from the literature up to 60 days. We then model numerically, using a Bayesian approach, the GRANDMA and HXMT-LE afterglow observations, that we augment with Swift-XRT and additional optical/NIR observations reported in the literature. We find that the GRB afterglow, extinguished by a large dust column, is most likely behind a combination of a large Milky-Way dust column combined with moderate low-metallicity dust in the host galaxy. Using the GRANDMA+HXMT-LE+XRT dataset, we find that the simplest model, where the observed afterglow is produced by synchrotron radiation at the forward external shock during the deceleration of a top-hat relativistic jet by a uniform medium, fits the multi-wavelength observations only moderately well, with a tension between the observed temporal and spectral evolution. This tension is confirmed when using the extended dataset. We find that the consideration of a jet structure (Gaussian or power-law), the inclusion of synchrotron self-Compton emission, or the presence of an underlying supernova do not improve the predictions, showing that the modelling of GRB22109A will require going beyond the most standard GRB afterglow model. Placed in the global context of GRB optical afterglows, we find the afterglow of GRB 221009A is luminous but not extraordinarily so, highlighting that some aspects of this GRB do not deviate from the global known sample despite its extreme energetics and the peculiar afterglow evolution.Comment: Accepted to ApJL for the special issue, 37 pages, 23 pages main text, 6 tables, 13 figure

    The Rise of Three Rs Centres and Platforms in Europe*

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    Public awareness and discussion about animal experiments and replacement methods has greatly increased in recent years. The term 'the Three Rs', which stands for the Replacement, Reduction and Refinement of animal experiments, is inseparably linked in this context. A common goal within the Three Rs scientific community is to develop predictive non-animal models and to better integrate all available data from in vitro, in silico and omics technologies into regulatory decision-making processes regarding, for example, the toxicity of chemicals, drugs or food ingredients. In addition, it is a general concern to implement (human) non-animal methods in basic research. Toward these efforts, there has been an ever-increasing number of Three Rs centres and platforms established over recent years - not only to develop novel methods, but also to disseminate knowledge and help to implement the Three Rs principles in policies and education. The adoption of Directive 2010/63/EU on the protection of animals used for scientific purposes gave a strong impetus to the creation of Three Rs initiatives, in the form of centres and platforms. As the first of a series of papers, this article gives an overview of the European Three Rs centres and platforms, and their historical development. The subsequent articles, to be published over the course of ATLA's 50th Anniversary year, will summarise the current focus and tasks as well as the future and the plans of the Three Rs centres and platforms. The Three Rs centres and platforms are very important points of contact and play an immense role in their respective countries as 'on the ground' facilitators of Directive 2010/63/EU. They are also invaluable for the widespread dissemination of information and for promoting implementation of the Three Rs in general

    The Current Status and Work of Three Rs Centres and Platforms in Europe*

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    The adoption of Directive 2010/63/EU on the protection of animals used for scientific purposes has given a major push to the formation of Three Rs initiatives in the form of centres and platforms. These centres and platforms are dedicated to the so-called Three Rs, which are the Replacement, Reduction and Refinement of animal use in experiments. ATLA's 50th Anniversary year has seen the publication of two articles on European Three Rs centres and platforms. The first of these was about the progressive rise in their numbers and about their founding history; this second part focuses on their current status and activities. This article takes a closer look at their financial and organisational structures, describes their Three Rs focus and core activities (dissemination, education, implementation, scientific quality/translatability, ethics), and presents their areas of responsibility and projects in detail. This overview of the work and diverse structures of the Three Rs centres and platforms is not only intended to bring them closer to the reader, but also to provide role models and show examples of how such Three Rs centres and platforms could be made sustainable. The Three Rs centres and platforms are very important focal points and play an immense role as facilitators of Directive 2010/63/EU 'on the ground' in their respective countries. They are also invaluable for the wide dissemination of information and for promoting the implementation of the Three Rs in general
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