Gene set bagging for estimating replicability of gene set analyses

Background: Significance analysis plays a major role in identifying and ranking genes, transcription factor binding sites, DNA methylation regions, and other high-throughput features for association with disease. We propose a new approach, called gene set bagging, for measuring the stability of ranking procedures using predefined gene sets. Gene set bagging involves resampling the original high-throughput data, performing gene-set analysis on the resampled data, and confirming that biological categories replicate. This procedure can be thought of as bootstrapping gene-set analysis and can be used to determine which are the most reproducible gene sets. Results: Here we apply this approach to two common genomics applications: gene expression and DNA methylation. Even with state-of-the-art statistical ranking procedures, significant categories in a gene set enrichment analysis may be unstable when subjected to resampling. Conclusions: We demonstrate that gene lists are not necessarily stable, and therefore additional steps like gene set bagging can improve biological inference of gene set analysis.Comment: 3 Figure

Saddle-point van Hove singularity and the phase diagram of high-Tc cuprates

We examine the generic phase behavior of high-Tc cuprate superconductors in terms a universal van Hove singularity in the strongly overdoped region. Using a rigid ARPES-derived dispersion we solve the BCS gap equation and show that the pairing interaction or pairing energy cutoff must be a rapidly declining function of doping. This result is prejudicial to a phonon-based pairing interaction and more consistent with a magnetic or magnetically enhanced interaction.Comment: 5 pages, 2 figures, submitted to Physical Review

Overcoming the boundary layer turbulence at Dome C: ground-layer adaptive optics versus tower

The unique atmospheric conditions present at sites such as Dome C on the Antarctic plateau are very favorable for high spatial resolution astronomy. At Dome C, the majority of the optical turbulence is confined to a 30 to 40 m thick stable boundary layer that results from the strong temperature inversion created by the heat exchange between the air and the ice-covered ground. To fully realize the potential of the exceptionally calm free atmosphere, this boundary layer must be overcome. In this article we compare the performance of two methods proposed to beat the boundary layer: mounting a telescope on a tower that physically puts it above the turbulent layer, and installing a telescope at ground level with a ground-layer adaptive optics system. A case is also made to combine these two methods to further improve the image quality

Crystal structures of four indole derivatives as possible cannabinoid allosteric antagonists

Acknowledgements We thank the EPSRC National Crystallography Service (University of Southampton) for the data collections and the EPSRC National Mass Spectrometry Service (University of Swansea) for the HRMS data. We thank John Low for carrying out the Cambridge Database survey.Peer reviewedPublisher PD

Thermodynamic properties of Bi2Sr2CaCu2O8 calculated from the electronic dispersion

The electronic dispersion for Bi2Sr2CaCu2O(8+d) has been determined from angle-resolved photoelectron spectroscopy (ARPES). From this dispersion we calculate the entropy and superfluid density. Even with no adjustable parameters we obtain an exceptional match with experimental data across the entire phase diagram, thus indirectly confirming both the ARPES and thermodynamic data. The van Hove singularity is crossed in the overdoped region giving a distinctive linear-in-T temperature dependence in the superfluid density there.Comment: 5 pages, 4 figures, submitted to Physical Review Letter

Pulse Profiles, Accretion Column Dips and a Flare in GX 1+4 During a Faint State

The Rossi X-ray Timing Explorer (RXTE) spacecraft observed the X-ray pulsar GX 1+4 for a period of 34 hours on July 19/20 1996. The source faded from an intensity of ~20 mCrab to a minimum of <~0.7 mCrab and then partially recovered towards the end of the observation. This extended minimum lasted ~40,000 seconds. Phase folded light curves at a barycentric rotation period of 124.36568 +/- 0.00020 seconds show that near the center of the extended minimum the source stopped pulsing in the traditional sense but retained a weak dip feature at the rotation period. Away from the extended minimum the dips are progressively narrower at higher energies and may be interpreted as obscurations or eclipses of the hot spot by the accretion column. The pulse profile changed from leading-edge bright before the extended minimum to trailing-edge bright after it. Data from the Burst and Transient Source Experiment (BATSE) show that a torque reversal occurred <10 days after our observation. Our data indicate that the observed rotation departs from a constant period with a Pdot/P value of ~-1.5% per year at a 4.5 sigma significance. We infer that we may have serendipitously obtained data, with high sensitivity and temporal resolution about the time of an accretion disk spin reversal. We also observed a rapid flare which had some precursor activity, close to the center of the extended minimum.Comment: 19 pages, 6 figures, accepted for publication in Astrophysical Journal (tentatively scheduled for vol. 529 #1, 20 Jan 2000