Ribofsm: Frequent Subgraph Mining For the Discovery of RNA Structures and Interactions

Frequent subgraph mining is a useful method for extracting meaningful patterns from a set of graphs or a single large graph. Here, the graph represents all possible RNA structures and interactions. Patterns that are significantly more frequent in this graph over a random graph are extracted. We hypothesize that these patterns are most likely to represent biological mechanisms. The graph representation used is a directed dual graph, extended to handle intermolecular interactions. The graph is sampled for subgraphs, which are labeled using a canonical labeling method and counted. The resulting patterns are compared to those created from a randomized dataset and scored. The algorithm was applied to the mitochondrial genome of the kinetoplastid species Trypanosoma brucei, which has a unique RNA editing mechanism. The most significant patterns contain two stem-loops, indicative of gRNA, and represent interactions of these structures with target mRNA

Utilité de l’exposé magistral en ligne dans la formation universitaire en sciences de l’activité physique

La formation professionnelle en sciences de l’activité physique à l’université est principalement axée sur l’acquisition de savoirs et de savoir-faire. En particulier, la faible participation des étudiants à la formation théorique est une problématique importante. Le but de cette étude est de vérifier la perception de l’utilité de deux exposés magistraux en ligne dans la formation théorique. Deux formulaires placés en ligne ont permis de recueillir auprès des étudiants les avantages et les inconvénients associés à la mise en œuvre de ce dispositif de formation. Les réponses données par les étudiants sont discutées à la lumière du modèle de St-Yves (1982) qui identifie les conditions internes et externes au déroulement du processus d’enseignement-apprentissage. Plus de 43 des 53 répondants considèrent ces exposés magistraux en ligne utiles. L’avantage majeur réside dans l’accès en tout temps aux exposés. L’inconvénient majeur consiste en l’absence d’interaction sur-le-champ. L’ajout d’un forum de discussion en ligne constitue fort probablement une solution de premier plan.The training of professional specialists in the field of physical activity is based on the acquisition of knowledge and know-how. Practical courses are preferred to theoretical courses. As a result, students often skip lectures. The purpose of this study is to analyze the utility of short online lectures. Two online questionnaires made of closed and open questions respectively were emailed to the students. The advantages and disadvantages are analyzed using the model of St-Yves (1982) who considers the process of teaching and learning as a function of internal and external conditions. More than 43 of the 53 students who answered the questionnaires found the online lectures useful. The major advantage is a 24 hour access to the online lecture and the major disadvantage is the lack of interaction with the teacher. A likely solution is the addition of an online forum to the lecture

Replicating financial market dynamics with a simple self-organized critical lattice model

We explore a simple lattice field model intended to describe statistical properties of high frequency financial markets. The model is relevant in the cross-disciplinary area of econophysics. Its signature feature is the emergence of a self-organized critical state. This implies scale invariance of the model, without tuning parameters. Prominent results of our simulation are time series of gains, prices, volatility, and gains frequency distributions, which all compare favorably to features of historical market data. Applying a standard GARCH(1,1) fit to the lattice model gives results that are almost indistinguishable from historical NASDAQ data.Comment: 20 pages, 33 figure

High frequency intrinsic modes in El Ni\~no Southern Oscillation Index

Recent $daily$ data of the Southern Oscillation Index have been analyzed. The power spectrum indicates major intrinsic geophysical short periods. We find interesting ``high frequency'' oscillations at 24, 27, 37, 76, 100 and 365 days. In particular the 24 days peaks may correspond to the Branstator-Kushnir wave, the 27 days may be due to the moon effect rotation, the 37 days peaks is most probably related to the Madden and Julian Oscillation. It is not yet clear the explanations for the 76 days which may be associated with interseasonal oscillation in the tropical atmosphere; the 100 days could be resulting from a mere beat between the 37 and 27 periods, or the 76 and 365 days. Next these periods are used to reconstruct the signal and to produce a forecast for the next 9 months, at the time of writing. After cleansing the signal of those periodicities a detrended fluctuation analysis is performed to reveal the nature of the stochastic structures in the signal and whether specific correlation can be found. We study the evolution of the distribution of first return times, in particular between $extreme$ $events$. A markedly significant difference from the expected distribution for uncorrelated events is found.Comment: accepted for publication on Physica

Can Clustal-style progressive pairwise alignment of multiple sequences be used in RNA secondary structure prediction?

<p>Abstract</p> <p>Background</p> <p>In ribonucleic acid (RNA) molecules whose function depends on their final, folded three-dimensional shape (such as those in ribosomes or spliceosome complexes), the secondary structure, defined by the set of internal basepair interactions, is more consistently conserved than the primary structure, defined by the sequence of nucleotides.</p> <p>Results</p> <p>The research presented here investigates the possibility of applying a progressive, pairwise approach to the alignment of multiple RNA sequences by simultaneously predicting an energy-optimized consensus secondary structure. We take an existing algorithm for finding the secondary structure common to two RNA sequences, Dynalign, and alter it to align profiles of multiple sequences. We then explore the relative successes of different approaches to designing the tree that will guide progressive alignments of sequence profiles to create a multiple alignment and prediction of conserved structure.</p> <p>Conclusion</p> <p>We have found that applying a progressive, pairwise approach to the alignment of multiple ribonucleic acid sequences produces highly reliable predictions of conserved basepairs, and we have shown how these predictions can be used as constraints to improve the results of a single-sequence structure prediction algorithm. However, we have also discovered that the amount of detail included in a consensus structure prediction is highly dependent on the order in which sequences are added to the alignment (the guide tree), and that if a consensus structure does not have sufficient detail, it is less likely to provide useful constraints for the single-sequence method.</p

FIRRM/C1orf112 is synthetic lethal with PICH and mediates RAD51 dynamics

Joint DNA molecules are natural byproducts of DNA replication and repair. Persistent joint molecules give rise to ultrafine DNA bridges (UFBs) in mitosis, compromising sister chromatid separation. The DNA translocase PICH (ERCC6L) has a central role in UFB resolution. A genome-wide loss-of-function screen is performed to identify the genetic context of PICH dependency. In addition to genes involved in DNA condensation, centromere stability, and DNA-damage repair, we identify FIGNL1-interacting regulator of recombination and mitosis (FIRRM), formerly known as C1orf112. We find that FIRRM interacts with and stabilizes the AAA + ATPase FIGNL1. Inactivation of either FIRRM or FIGNL1 results in UFB formation, prolonged accumulation of RAD51 at nuclear foci, and impaired replication fork dynamics and consequently impairs genome maintenance. Combined, our data suggest that inactivation of FIRRM and FIGNL1 dysregulates RAD51 dynamics at replication forks, resulting in persistent DNA lesions and a dependency on PICH to preserve cell viability. </p

A search for structurally similar cellular internal ribosome entry sites

Internal ribosome entry sites (IRES) allow ribosomes to be recruited to mRNA in a cap-independent manner. Some viruses that impair cap-dependent translation initiation utilize IRES to ensure that the viral RNA will efficiently compete for the translation machinery. IRES are also employed for the translation of a subset of cellular messages during conditions that inhibit cap-dependent translation initiation. IRES from viruses like Hepatitis C and Classical Swine Fever virus share a similar structure/function without sharing primary sequence similarity. Of the cellular IRES structures derived so far, none were shown to share an overall structural similarity. Therefore, we undertook a genome-wide search of human 5′UTRs (untranslated regions) with an empirically derived structure of the IRES from the key inhibitor of apoptosis, X-linked inhibitor of apoptosis protein (XIAP), to identify novel IRES that share structure/function similarity. Three of the top matches identified by this search that exhibit IRES activity are the 5′UTRs of Aquaporin 4, ELG1 and NF-kappaB repressing factor (NRF). The structures of AQP4 and ELG1 IRES have limited similarity to the XIAP IRES; however, they share trans-acting factors that bind the XIAP IRES. We therefore propose that cellular IRES are not defined by overall structure, as viral IRES, but are instead dependent upon short motifs and trans-acting factors for their function

Repertoire Enhancement with Adoptively Transferred Female Lymphocytes Controls the Growth of Pre-Implanted Murine Prostate Cancer

In prostate cancer, genes encoding androgen-regulated, Y-chromosome-encoded, and tissue-specific antigens may all be overexpressed. In the adult male host, however, most high affinity T cells targeting these potential tumor rejection antigens will be removed during negative selection. In contrast, the female mature T-cell repertoire should contain abundant precursors capable of recognizing these classes of prostate cancer antigens and mediating effective anti-tumor immune responses.We find that syngeneic TRAMP-C2 prostatic adenocarcinoma cells are spontaneously rejected in female hosts. Adoptive transfer of naïve female lymphocytes to irradiated male hosts bearing pre-implanted TRAMP-C2 tumor cells slows tumor growth and mediates tumor rejection in some animals. The success of this adoptive transfer was dependent on the transfer of female CD4 T cells and independent of the presence of CD25-expressing regulatory T cells in the transferred lymphocytes. We identify in female CD4 T cells stimulated with TRAMP-C2 a dominant MHC II-restricted response to the Y-chromosome antigen DBY. Furthermore, CD8 T cell responses in female lymphocytes to the immunodominant MHC I-restricted antigen SPAS-1 are markedly increased compared to male mice. Finally, we find no exacerbation of graft-versus-host disease in either syngeneic or minor-antigen mismatched allogeneic lymphocyte adoptive transfer models by using female into male versus male into male cells.This study shows that adoptively transferred female lymphocytes, particularly CD4 T cells, can control the outgrowth of pre-implanted prostatic adenocarcinoma cells. This approach does not significantly worsen graft-versus-host responses suggesting it may be viable in the clinic. Further, enhancing the available immune repertoire with female-derived T cells may provide an excellent pool of prostate cancer reactive T cells for further augmentation by combination with either vaccination or immune regulatory blockade strategies

Characteristics of the diffuse astrophysical electron and tau neutrino flux with six years of IceCube high energy cascade data

We report on the first measurement of the astrophysical neutrino flux using particle showers (cascades) in IceCube data from 2010 -- 2015. Assuming standard oscillations, the astrophysical neutrinos in this dedicated cascade sample are dominated ($\sim 90 \%$) by electron and tau flavors. The flux, observed in the sensitive energy range from $16\,\mathrm{TeV}$ to $2.6\,\mathrm{PeV}$, is consistent with a single power-law model as expected from Fermi-type acceleration of high energy particles at astrophysical sources. We find the flux spectral index to be $\gamma=2.53\pm0.07$ and a flux normalization for each neutrino flavor of $\phi_{astro} = 1.66^{+0.25}_{-0.27}$ at $E_{0} = 100\, \mathrm{TeV}$, in agreement with IceCube's complementary muon neutrino results and with all-neutrino flavor fit results. In the measured energy range we reject spectral indices $\gamma\leq2.28$ at $\ge3\sigma$ significance level. Due to high neutrino energy resolution and low atmospheric neutrino backgrounds, this analysis provides the most detailed characterization of the neutrino flux at energies below $\sim100\,{\rm{TeV}}$ compared to previous IceCube results. Results from fits assuming more complex neutrino flux models suggest a flux softening at high energies and a flux hardening at low energies (p-value $\ge 0.06$). The sizable and smooth flux measured below $\sim 100\,{\rm{TeV}}$ remains a puzzle. In order to not violate the isotropic diffuse gamma-ray background as measured by the Fermi-LAT, it suggests the existence of astrophysical neutrino sources characterized by dense environments which are opaque to gamma-rays.Comment: 4 figures, 4 tables, includes supplementary materia