Computing the Partition Function for Kinetically Trapped RNA Secondary Structures

An RNA secondary structure is locally optimal if there is no lower energy structure that can be obtained by the addition or removal of a single base pair, where energy is defined according to the widely accepted Turner nearest neighbor model. Locally optimal structures form kinetic traps, since any evolution away from a locally optimal structure must involve energetically unfavorable folding steps. Here, we present a novel, efficient algorithm to compute the partition function over all locally optimal secondary structures of a given RNA sequence. Our software, RNAlocopt runs in time and space. Additionally, RNAlocopt samples a user-specified number of structures from the Boltzmann subensemble of all locally optimal structures. We apply RNAlocopt to show that (1) the number of locally optimal structures is far fewer than the total number of structures – indeed, the number of locally optimal structures approximately equal to the square root of the number of all structures, (2) the structural diversity of this subensemble may be either similar to or quite different from the structural diversity of the entire Boltzmann ensemble, a situation that depends on the type of input RNA, (3) the (modified) maximum expected accuracy structure, computed by taking into account base pairing frequencies of locally optimal structures, is a more accurate prediction of the native structure than other current thermodynamics-based methods. The software RNAlocopt constitutes a technical breakthrough in our study of the folding landscape for RNA secondary structures. For the first time, locally optimal structures (kinetic traps in the Turner energy model) can be rapidly generated for long RNA sequences, previously impossible with methods that involved exhaustive enumeration. Use of locally optimal structure leads to state-of-the-art secondary structure prediction, as benchmarked against methods involving the computation of minimum free energy and of maximum expected accuracy. Web server and source code available at http://bioinformatics.bc.edu/clotelab/RNAlocopt/

CodingMotif: exact determination of overrepresented nucleotide motifs in coding sequences

<p>Abstract</p> <p>Background</p> <p>It has been increasingly appreciated that coding sequences harbor regulatory sequence motifs in addition to encoding for protein. These sequence motifs are expected to be overrepresented in nucleotide sequences bound by a common protein or small RNA. However, detecting overrepresented motifs has been difficult because of interference by constraints at the protein level. Sampling-based approaches to solve this problem based on codon-shuffling have been limited to exploring only an infinitesimal fraction of the sequence space and by their use of parametric approximations.</p> <p>Results</p> <p>We present a novel <it>O</it>(<it>N</it>(log <it>N</it>)²)-time algorithm, CodingMotif, to identify nucleotide-level motifs of unusual copy number in protein-coding regions. Using a new dynamic programming algorithm we are able to exhaustively calculate the distribution of the number of occurrences of a motif over all possible coding sequences that encode the same amino acid sequence, given a background model for codon usage and dinucleotide biases. Our method takes advantage of the sparseness of loci where a given motif can occur, greatly speeding up the required convolution calculations. Knowledge of the distribution allows one to assess the exact non-parametric p-value of whether a given motif is over- or under- represented. We demonstrate that our method identifies known functional motifs more accurately than sampling and parametric-based approaches in a variety of coding datasets of various size, including ChIP-seq data for the transcription factors NRSF and GABP.</p> <p>Conclusions</p> <p>CodingMotif provides a theoretically and empirically-demonstrated advance for the detection of motifs overrepresented in coding sequences. We expect CodingMotif to be useful for identifying motifs in functional genomic datasets such as DNA-protein binding, RNA-protein binding, or microRNA-RNA binding within coding regions. A software implementation is available at <url>http://bioinformatics.bc.edu/chuanglab/codingmotif.tar</url></p

LIVE COLOR PATTERNS DIAGNOSE SPECIES: A TALE OF TWO HERICHTHYS

The Rio Grande Cichlid, Herichthys cyanoguttatus, is native to the drainages of the Gulf Coast of northern Mexico and southern Texas and has been introduced at several sites in the US. Previous observations have suggested that non-native populations in Louisiana that are currently recognized as H. cyanoguttatus resemble another species, the Lowland Cichlid, H. carpintis. Traditional morphological and genetic techniques have been insufficient to differentiate these species, but H. carpintis has been reported to differ from H. cyanoguttatus in color pattern, so we turned to novel electronic photo archives to determine the identity of the species introduced in Louisiana. First, we used the public databases Nonindigenous Aquatic Species Database and Fishes of Texas to infer the historical distributions of these species in the US. We then used museum specimens, live specimens, and two additional databases, The Cichlid Room Companion and iNaturalist, to compare morphology and color patterns among individuals obtained from their native and introduced ranges in Mexico, Texas, and Louisiana. Our general observations found that H. cf. cyanoguttatus from Louisiana tended to have an obliquely oriented mouth and a more rounded ventral profile than H. cyanoguttatus from Texas, consistent with previous descriptions of H. carpintis, but our morphological analyses were unable to identify any significant differences among populations. Our analyses of color patterns found that H. cf. cyanoguttatus from Louisiana had larger iridescent spots than H. cyanoguttatus from Texas as well as black breeding coloration that extended anteriorly to the tip of the mouth, characters consistent with H. carpintis. Our observations indicate that at least some of the cichlids introduced in Louisiana are not H. cyanoguttatus but are instead H. carpintis, and that their presence there is likely due to release by humans. This is the first record of H. carpintis establishing a population in the US. Understanding the biology of not one, but two, species of Herichthys will be necessary to predict and mitigate their continued colonization of new environments in the US.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167241/1/UMMZ MP 209.pdfDescription of UMMZ MP 209.pdf : Main ArticleSEL

Cassini RADAR Sequence Planning and Instrument Performance

The Cassini RADAR is a multimode instrument used to map the surface of Titan, the atmosphere of Saturn, the Saturn ring system, and to explore the properties of the icy satellites. Four different active mode bandwidths and a passive radiometer mode provide a wide range of flexibility in taking measurements. The scatterometer mode is used for real aperture imaging of Titan, high-altitude (around 20 000 km) synthetic aperture imaging of Titan and Iapetus, and long range (up to 700 000 km) detection of disk integrated albedos for satellites in the Saturn system. Two SAR modes are used for high- and medium-resolution (300-1000 m) imaging of Titan's surface during close flybys. A high-bandwidth altimeter mode is used for topographic profiling in selected areas with a range resolution of about 35 m. The passive radiometer mode is used to map emission from Titan, from Saturn's atmosphere, from the rings, and from the icy satellites. Repeated scans with differing polarizations using both active and passive data provide data that can usefully constrain models of surface composition and structure. The radar and radiometer receivers show very good stability, and calibration observations have provided an absolute calibration good to about 1.3 dB. Relative uncertainties within a pass and between passes can be even smaller. Data are currently being processed and delivered to the planetary data system at quarterly intervals one year after being acquired

An Investigation into the Determining Factors of Zoo Visitor Attendances in UK Zoos

The debate as to which animals are most beneficial to keep in zoos in terms of financial and conservative value is readily disputed; however, demographic factors have also been shown to relate to visitor numbers on an international level. The main aims of this research were: (1) To observe the distribution and location of zoos across the UK, (2) to develop a way of calculating zoo popularity in terms of the species kept within a collection and (3) to investigate the factors related to visitor numbers regarding admission costs, popularity of the collection in terms of the species kept and local demographic factors. Zoo visitor numbers were positively correlated with generated popularity ratings for zoos based on the species kept within a collection and admission prices (Pearson correlation: n = 34, r = 0.268, P = 0.126 and n = 34, r = −0.430, P = 0.011). Animal collections are aggregated around large cities and tourist regions, particularly coastal areas. No relationship between demographic variables and visitor numbers was found (Pearson correlation: n = 34, r = 0.268, P = 0.126), which suggests that the popularity of a zoo's collection relative to the types and numbers of species kept is more indicative of a collection's visitor numbers than its surrounding demographic figures. Zoos should incorporate generating high popularity scores as part of their collection planning strategies, to ensure that they thrive in the future, not only as tourist attractions but also as major conservation organizations

Computing folding pathways between RNA secondary structures

Given an RNA sequence and two designated secondary structures A, B, we describe a new algorithm that computes a nearly optimal folding pathway from A to B. The algorithm, RNAtabupath, employs a tabu semi-greedy heuristic, known to be an effective search strategy in combinatorial optimization. Folding pathways, sometimes called routes or trajectories, are computed by RNAtabupath in a fraction of the time required by the barriers program of Vienna RNA Package. We benchmark RNAtabupath with other algorithms to compute low energy folding pathways between experimentally known structures of several conformational switches. The RNApathfinder web server, source code for algorithms to compute and analyze pathways and supplementary data are available at http://bioinformatics.bc.edu/clotelab/RNApathfinder

The right-hemisphere and valence hypotheses: could they both be right (and sometimes left)?

The two halves of the brain are believed to play different roles in emotional processing, but the specific contribution of each hemisphere continues to be debated. The right-hemisphere hypothesis suggests that the right cerebrum is dominant for processing all emotions regardless of affective valence, whereas the valence specific hypothesis posits that the left hemisphere is specialized for processing positive affect while the right hemisphere is specialized for negative affect. Here, healthy participants viewed two split visual-field facial affect perception tasks during functional magnetic resonance imaging, one presenting chimeric happy faces (i.e. half happy/half neutral) and the other presenting identical sad chimera (i.e. half sad/half neutral), each masked immediately by a neutral face. Results suggest that the posterior right hemisphere is generically activated during non-conscious emotional face perception regardless of affective valence, although greater activation is produced by negative facial cues. The posterior left hemisphere was generally less activated by emotional faces, but also appeared to recruit bilateral anterior brain regions in a valence-specific manner. Findings suggest simultaneous operation of aspects of both hypotheses, suggesting that these two rival theories may not actually be in opposition, but may instead reflect different facets of a complex distributed emotion processing system

Maximum expected accuracy structural neighbors of an RNA secondary structure

International audienceBACKGROUND: Since RNA molecules regulate genes and control alternative splicing by allostery, it is important to develop algorithms to predict RNA conformational switches. Some tools, such as paRNAss, RNAshapes and RNAbor, can be used to predict potential conformational switches; nevertheless, no existent tool can detect general (i.e., not family specific) entire riboswitches (both aptamer and expression platform) with accuracy. Thus, the development of additional algorithms to detect conformational switches seems important, especially since the difference in free energy between the two metastable secondary structures may be as large as 15-20 kcal/mol. It has recently emerged that RNA secondary structure can be more accurately predicted by computing the maximum expected accuracy (MEA) structure, rather than the minimum free energy (MFE) structure. RESULTS: Given an arbitrary RNA secondary structure S₀ for an RNA nucleotide sequence a = a₁,..., a(n), we say that another secondary structure S of a is a k-neighbor of S₀, if the base pair distance between S₀ and S is k. In this paper, we prove that the Boltzmann probability of all k-neighbors of the minimum free energy structure S₀ can be approximated with accuracy ε and confidence 1 - p, simultaneously for all 0 ≤ k N(ε,p,K)=Φ⁻¹(p/2K)²/4ε², where Φ(z) is the cumulative distribution function (CDF) for the standard normal distribution. We go on to describe the algorithm RNAborMEA, which for an arbitrary initial structure S₀ and for all values 0 ≤ k < K, computes the secondary structure MEA(k), having maximum expected accuracy over all k-neighbors of S₀. Computation time is O(n³ * K²), and memory requirements are O(n² * K). We analyze a sample TPP riboswitch, and apply our algorithm to the class of purine riboswitches. CONCLUSIONS: The approximation of RNAbor by sampling, with rigorous bound on accuracy, together with the computation of maximum expected accuracy k-neighbors by RNAborMEA, provide additional tools toward conformational switch detection. Results from RNAborMEA are quite distinct from other tools, such as RNAbor, RNAshapes and paRNAss, hence may provide orthogonal information when looking for suboptimal structures or conformational switches. Source code for RNAborMEA can be downloaded from http://sourceforge.net/projects/rnabormea/ or http://bioinformatics.bc.edu/clotelab/RNAborMEA/

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

The Science of Pronominal Usage: He and It in Co-Reference to Inanimate Objects in Late Middle English Texts on Alchemy

This is the author's accepted manuscript. The published version can be found at http://dx.doi.org/10.1177/0075424210384225This article explores the variation between he and it in coreference to inanimate entities (such as mercury, sulfur, and salt). Using alchemical texts from the fifteenth century as material, the article demonstrates that there was much more variation in pronominal reference in this period than has previously been shown. Of the possible explanations suggested by previous research, the earlier grammatical gender system and transference from Latin do not seem to play a role, while pronoun clustering and pronominal reanalysis appear to influence the quantitative distribution. The scale of individuation used by Siemund and Stenroos to explain similar usage is shown not to be a straightforward predictor. Other factors such as personification and perceived similarities between animate and inanimate entities may affect the degree of perceived individuation. The choice of he over she seems to be influenced by pronominal reanalysis and straightforward personification in some cases. In other instances, it is speculated that the he usage reflects (stereotypical) gender conceptions in the Middle Ages