Bayesian detection of periodic mRNA time profiles without use of training examples

BACKGROUND: Detection of periodically expressed genes from microarray data without use of known periodic and non-periodic training examples is an important problem, e.g. for identifying genes regulated by the cell-cycle in poorly characterised organisms. Commonly the investigator is only interested in genes expressed at a particular frequency that characterizes the process under study but this frequency is seldom exactly known. Previously proposed detector designs require access to labelled training examples and do not allow systematic incorporation of diffuse prior knowledge available about the period time. RESULTS: A learning-free Bayesian detector that does not rely on labelled training examples and allows incorporation of prior knowledge about the period time is introduced. It is shown to outperform two recently proposed alternative learning-free detectors on simulated data generated with models that are different from the one used for detector design. Results from applying the detector to mRNA expression time profiles from S. cerevisiae showsthat the genes detected as periodically expressed only contain a small fraction of the cell-cycle genes inferred from mutant phenotype. For example, when the probability of false alarm was equal to 7%, only 12% of the cell-cycle genes were detected. The genes detected as periodically expressed were found to have a statistically significant overrepresentation of known cell-cycle regulated sequence motifs. One known sequence motif and 18 putative motifs, previously not associated with periodic expression, were also over represented. CONCLUSION: In comparison with recently proposed alternative learning-free detectors for periodic gene expression, Bayesian inference allows systematic incorporation of diffuse a priori knowledge about, e.g. the period time. This results in relative performance improvements due to increased robustness against errors in the underlying assumptions. Results from applying the detector to mRNA expression time profiles from S. cerevisiae include several new findings that deserve further experimental studies

Does using a foreign language reduce mental imagery?

In a recent article, Hayakawa and Keysar (2018) propose that mental imagery is less vivid when evoked in a foreign than in a native language. The authors argue that reduced mental imagery could even account for moral foreign language effects, whereby moral choices become more utilitarian when made in a foreign language. Here we demonstrate that Hayakawa and Keysar's (2018) key results are better explained by reduced language comprehension in a foreign language than by less vivid imagery. We argue that the paradigm used in Hayakawa and Keysar (2018) does not provide a satisfactory test of reduced imagery and we discuss an alternative paradigm based on recent experimental developments

Improved variance estimation of classification performance via reduction of bias caused by small sample size

BACKGROUND: Supervised learning for classification of cancer employs a set of design examples to learn how to discriminate between tumors. In practice it is crucial to confirm that the classifier is robust with good generalization performance to new examples, or at least that it performs better than random guessing. A suggested alternative is to obtain a confidence interval of the error rate using repeated design and test sets selected from available examples. However, it is known that even in the ideal situation of repeated designs and tests with completely novel samples in each cycle, a small test set size leads to a large bias in the estimate of the true variance between design sets. Therefore different methods for small sample performance estimation such as a recently proposed procedure called Repeated Random Sampling (RSS) is also expected to result in heavily biased estimates, which in turn translates into biased confidence intervals. Here we explore such biases and develop a refined algorithm called Repeated Independent Design and Test (RIDT). RESULTS: Our simulations reveal that repeated designs and tests based on resampling in a fixed bag of samples yield a biased variance estimate. We also demonstrate that it is possible to obtain an improved variance estimate by means of a procedure that explicitly models how this bias depends on the number of samples used for testing. For the special case of repeated designs and tests using new samples for each design and test, we present an exact analytical expression for how the expected value of the bias decreases with the size of the test set. CONCLUSION: We show that via modeling and subsequent reduction of the small sample bias, it is possible to obtain an improved estimate of the variance of classifier performance between design sets. However, the uncertainty of the variance estimate is large in the simulations performed indicating that the method in its present form cannot be directly applied to small data sets

Revealing cell cycle control by combining model-based detection of periodic expression with novel cis-regulatory descriptors

<p>Abstract</p> <p>Background</p> <p>We address the issue of explaining the presence or absence of phase-specific transcription in budding yeast cultures under different conditions. To this end we use a model-based detector of gene expression periodicity to divide genes into classes depending on their behavior in experiments using different synchronization methods. While computational inference of gene regulatory circuits typically relies on expression similarity (clustering) in order to find classes of potentially co-regulated genes, this method instead takes advantage of known time profile signatures related to the studied process.</p> <p>Results</p> <p>We explain the regulatory mechanisms of the inferred periodic classes with <it>cis</it>-regulatory descriptors that combine upstream sequence motifs with experimentally determined binding of transcription factors. By systematic statistical analysis we show that periodic classes are best explained by combinations of descriptors rather than single descriptors, and that different combinations correspond to periodic expression in different classes. We also find evidence for additive regulation in that the combinations of <it>cis</it>-regulatory descriptors associated with genes periodically expressed in fewer conditions are frequently subsets of combinations associated with genes periodically expression in more conditions. Finally, we demonstrate that our approach retrieves combinations that are more specific towards known cell-cycle related regulators than the frequently used clustering approach.</p> <p>Conclusion</p> <p>The results illustrate how a model-based approach to expression analysis may be particularly well suited to detect biologically relevant mechanisms. Our new approach makes it possible to provide more refined hypotheses about regulatory mechanisms of the cell cycle and it can easily be adjusted to reveal regulation of other, non-periodic, cellular processes.</p

Counselling for burnout in Norwegian doctors: one year cohort study

Objective To investigate levels and predictors of change in dimensions of burnout after an intervention for stressed doctors

New Measurement of Compton Scattering from the Deuteron and an Improved Extraction of the Neutron Electromagnetic Polarizabilities

The electromagnetic polarizabilities of the nucleon are fundamental properties that describe its response to external electric and magnetic fields. They can be extracted from Compton-scattering data --- and have been, with good accuracy, in the case of the proton. In contradistinction, information for the neutron requires the use of Compton scattering from nuclear targets. Here we report a new measurement of elastic photon scattering from deuterium using quasimonoenergetic tagged photons at the MAX IV Laboratory in Lund, Sweden. These first new data in more than a decade effectively double the world dataset. Their energy range overlaps with previous experiments and extends it by 20 MeV to higher energies. An analysis using Chiral Effective Field Theory with dynamical \Delta(1232) degrees of freedom shows the data are consistent with and within the world dataset. After demonstrating that the fit is consistent with the Baldin sum rule, extracting values for the isoscalar nucleon polarizabilities and combining them with a recent result for the proton, we obtain the neutron polarizabilities as \alpha_n = [11.55 +/- 1.25(stat) +/- 0.2(BSR) +/- 0.8(th)] X 10^{-4} fm^3 and \beta_n = [3.65 -/+ 1.25(stat) +/- 0.2(BSR) -/+ 0.8(th)] X 10^{-4} fm3, with \chi^2 = 45.2 for 44 degrees of freedom.Comment: 6 pages, 3 figures, comments from Physical Review Letters Referees addresse

A measurement of the differential cross section for the two-body photodisintegration of 3He at theta_LAB = 90deg using tagged photons in the energy range 14 -- 31 MeV

The two-body photodisintegration of 3He has been investigated using tagged photons with energies from 14 -- 31 MeV at MAX-lab in Lund, Sweden. The two-body breakup channel was unambiguously identified by the (nonsimultaneous) detection of both protons and deuterons. This approach was made feasible by the over-determined kinematic situation afforded by the tagged-photon technique. Proton- and deuteron-energy spectra were measured using four silicon surface-barrier detector telescopes located at a laboratory angle of 90deg with respect to the incident photon-beam direction. Average statistical and systematic uncertainties of 5.7% and 6.6% in the differential cross section were obtained for 11 photon-energy bins with an average width of 1.2 MeV. The results are compared to previous experimental data measured at comparable photon energies as well as to the results of two recent Faddeev calculations which employ realistic potential models and take into account three-nucleon forces and final-state interactions. Both the accuracy and precision of the present data are improved over the previous measurements. The data are in good agreement with most of the previous results, and favor the inclusion of three-nucleon forces in the calculations.Comment: 12 pages, 13 figures; further Referee comments addresse

Search for anomaly-mediated supersymmetry breaking with the ATLAS detector based on a disappearing-track signature in pp collisions at root s=7 TeV

In models of anomaly-mediated supersymmetry breaking (AMSB), the lightest chargino is predicted to have a lifetime long enough to be detected in collider experiments. This letter explores AMSB scenarios in pp collisions at root s = 7 TeV by attempting to identify decaying charginos which result in tracks that appear to have few associated hits in the outer region of the tracking system. The search was based on data corresponding to an integrated luminosity of 1.02 fb(-1) collected with the ATLAS detector in 2011. The p(T) spectrum of candidate tracks is found to be consistent with the expectation from Standard Model background processes and constraints on the lifetime and the production cross section were obtained. In the minimal AMSB framework with m(3/2) &lt; 32 TeV, m(0) &lt; 1.5 TeV, tan beta = 5 and mu &gt; 0, a chargino having mass below 92 GeV and a lifetime between 0.5 ns and 2 ns is excluded at 95 % confidence level.ATLAS Collaboration, for complete list of authors see http://dx.doi.org/10.1140/epjc/s10052-012-1993-2</p