Two new functions in the WormBase Enrichment Suite

Genome-wide experiments routinely generate large amounts of data that can be hard to interpret biologically. A common approach to interpreting these results is to employ enrichment analyses of controlled languages, known as ontologies, that describe various biological parameters such as gene molecular or biological function. In C. elegans, three distinct ontologies, the Gene Ontology (GO), Anatomy Ontology (AO), and the Worm Phenotype Ontology (WPO) are used to annotate gene function, expression and phenotype, respectively (Ashburner et al. 2000; Lee and Sternberg, 2003; Schindelman et al. 2011). Previously, we developed software to test datasets for enrichment of anatomical terms, called the Tissue Enrichment Analysis (TEA) tool (Angeles-Albores and Sternberg, 2016). Using the same hypergeometric statistical method, we extend enrichment testing to include WPO and GO, offering a unified approach to enrichment testing in C. elegans. The WormBase Enrichment Suite can be accessed via a user-friendly interface at http://www.wormbase.org/tools/enrichment/tea/tea.cgi. To validate the tools, we analyzed a previously published extracellular vesicle (EV)-releasing neuron (EVN) signature gene set derived from dissociated ciliated EV neurons (Wang et al. 2015) using WormBase Enrichment Suite based on the WS262 WormBase release. TEA correctly identified the CEM, hook sensillum and IL2 neuron as enriched tissues. The top phenotype associated with the EVN signature was chemosensory behavior. Gene Ontology enrichment analysis showed that cell projection and cell body were the most enriched cellular components in this gene set, followed by the biological processes neuropeptide signaling pathway and vesicle localization further down. The tutorial script used to generate the figure above can be viewed at: https://github.com/dangeles/TissueEnrichmentAnalysis/blob/master/tutorial/Tutorial.ipynb The addition of Gene Enrichment Analysis (GEA) and Phenotype Enrichment Analysis (PEA) to WormBase marks an important step towards a unified set of analyses that can help researchers to understand genomic datasets. These enrichment analyses will allow the community to fully benefit from the data curation ongoing at WormBase

Tissue enrichment analysis for C. elegans genomics

Background: Over the last ten years, there has been explosive development in methods for measuring gene expression. These methods can identify thousands of genes altered between conditions, but understanding these datasets and forming hypotheses based on them remains challenging. One way to analyze these datasets is to associate ontologies (hierarchical, descriptive vocabularies with controlled relations between terms) with genes and to look for enrichment of specific terms. Although Gene Ontology (GO) is available for Caenorhabditis elegans, it does not include anatomical information. Results: We have developed a tool for identifying enrichment of C. elegans tissues among gene sets and generated a website GUI where users can access this tool. Since a common drawback to ontology enrichment analyses is its verbosity, we developed a very simple filtering algorithm to reduce the ontology size by an order of magnitude. We adjusted these filters and validated our tool using a set of 30 gold standards from Expression Cluster data in WormBase. We show our tool can even discriminate between embryonic and larval tissues and can even identify tissues down to the single-cell level. We used our tool to identify multiple neuronal tissues that are down-regulated due to pathogen infection in C. elegans. Conclusions: Our Tissue Enrichment Analysis (TEA) can be found within WormBase, and can be downloaded using Python’s standard pip installer. It tests a slimmed-down C. elegans tissue ontology for enrichment of specific terms and provides users with a text and graphic representation of the results

Long-range electronic reconstruction to a dxz,yzd_{xz,yz}-dominated Fermi surface below the LaAlO3_3/SrTiO3_3 interface

Low dimensionality, broken symmetry and easily-modulated carrier concentrations provoke novel electronic phase emergence at oxide interfaces. However, the spatial extent of such reconstructions - i.e. the interfacial "depth" - remains unclear. Examining LaAlO$_3$/SrTiO$_3$ heterostructures at previously unexplored carrier densities $n_{2D}\geq6.9\times10^{14}$ cm$^{-2}$, we observe a Shubnikov-de Haas effect for small in-plane fields, characteristic of an anisotropic 3D Fermi surface with preferential $d_{xz,yz}$ orbital occupancy extending over at least 100~nm perpendicular to the interface. Quantum oscillations from the 3D Fermi surface of bulk doped SrTiO$_3$ emerge simultaneously at higher $n_{2D}$. We distinguish three areas in doped perovskite heterostructures: narrow ($<20$ nm) 2D interfaces housing superconductivity and/or other emergent phases, electronically isotropic regions far ($>120$ nm) from the interface and new intermediate zones where interfacial proximity renormalises the electronic structure relative to the bulk.Comment: Supplementary material available at Scientific Reports websit

Limits on Radio Continuum Emission from a Sample of Candidate Contracting Starless Cores

We used the NRAO Very Large Array to search for 3.6 cm continuum emission from embedded protostars in a sample of 8 nearby ``starless'' cores that show spectroscopic evidence for infalling motions in molecular emission lines. We detect a total of 13 compact sources in the eight observed fields to 5 sigma limiting flux levels of typically 0.09 mJy. None of these sources lie within 1' of the central positions of the cores, and they are all likely background objects. Based on an extrapolation of the empirical correlation between the bolometric luminosity and 3.6 cm luminosity for the youngest protostars, these null-detections place upper limits of ~0.1 L_sun (d/140pc)^2 on the luminosities of protostellar sources embedded within these cores. These limits, together with the extended nature of the inward motions inferred from molecular line mapping (Lee et al. 2001), are inconsistent with the inside-out collapse model of singular isothermal spheres and suggest a less centrally condensed phase of core evolution during the earliest stages of star formation.Comment: Accepted to the Astronomical Journal; 12 pages, 1 figur

SPITZER: Accretion in Low Mass Stars and Brown Dwarfs in the Lambda Orionis Cluster

We present multi-wavelength optical and infrared photometry of 170 previously known low mass stars and brown dwarfs of the 5 Myr Collinder 69 cluster (Lambda Orionis). The new photometry supports cluster membership for most of them, with less than 15% of the previous candidates identified as probable non-members. The near infrared photometry allows us to identify stars with IR excesses, and we find that the Class II population is very large, around 25% for stars (in the spectral range M0 - M6.5) and 40% for brown dwarfs, down to 0.04 Msun, despite the fact that the H(alpha) equivalent width is low for a significant fraction of them. In addition, there are a number of substellar objects, classified as Class III, that have optically thin disks. The Class II members are distributed in an inhomogeneous way, lying preferentially in a filament running toward the south-east. The IR excesses for the Collinder 69 members range from pure Class II (flat or nearly flat spectra longward of 1 micron), to transition disks with no near-IR excess but excesses beginning within the IRAC wavelength range, to two stars with excess only detected at 24 micron. Collinder 69 thus appears to be at an age where it provides a natural laboratory for the study of primordial disks and their dissipation.Comment: ApJ, in pres

Effects of transcutaneous electric acupoint stimulation on drug use and responses to cue-induced craving: a pilot study

Background: Transcutaneous electric acupoint stimulation (TEAS) avoids the use of needles, and instead delivers a mild electric current at traditional acupoints. This technique has been used for treating heroin addiction, but has not been systematically tested for other drugs of abuse. This study aims to investigate the effects of TEAS on drug addiction. Methods: Volunteers who were either cocaine-dependent (n = 9) or cannabis-dependent (n = 11) but were not seeking treatment for their dependence participated in a within-subject, single-blind study. Treatment consisted of twice daily 30-minute sessions of TEAS or sham stimulation for 3.5 days. The active TEAS levels were individually adjusted to produce a distinct twitching response in the fingers, while the sham stimulation involved 2 minutes of stimulation at threshold levels followed by 28 minutes of stimulation below the detection levels. The participants recorded their drug use and drug cravings daily. At 1 hour after the last morning session of TEAS or sham stimulation, a cue-induced craving EEG evaluation was conducted. Event-related P300 potentials (ERPs) were recorded, sorted, and analyzed for specific image types (neutral objects, non-drug-related arousing images, or drug-related images). Results: TEAS treatment did not significantly reduce the drug use or drug cravings, or significantly alter the ERP peak voltage or latency to peak response. However, the TEAS treatment did significantly modulate several self-reported measures of mood and anxiety. Conclusion: The results of this pilot study with a limited sample size suggest that the acupoint stimulation techniques and protocol used in this trial alone do not significantly reduce cravings for or use of cocaine or cannabis. The findings that TEAS modulates mood and anxiety suggest that TEAS could be used as an adjunct in a multimodal therapy program to treat cocaine and cannabis dependence if confirmed in a full randomized controlled clinical trial

Horizons Inside Classical Lumps

Hopefully tex-able version.Comment: 13 pages, UMHEP-37

Wall-crossing of D4-D2-D0 and flop of the conifold

We discuss the wall-crossing of the BPS bound states of a non-compact holomorphic D4-brane with D2 and D0-branes on the conifold. We use the Kontsevich-Soibelman wall-crossing formula and analyze the BPS degeneracy in various chambers. In particular we obtain a relation between BPS degeneracies in two limiting attractor chambers related by a flop transition. Our result is consistent with known results and predicts BPS degeneracies in all chambers.Comment: 15 pages, 4 figures; v2: typos corrected; v3: minor changes, a reference added, version to be published in JHE