Methodological Issues in Multistage Genome-Wide Association Studies

Because of the high cost of commercial genotyping chip technologies, many investigations have used a two-stage design for genome-wide association studies, using part of the sample for an initial discovery of ``promising'' SNPs at a less stringent significance level and the remainder in a joint analysis of just these SNPs using custom genotyping. Typical cost savings of about 50% are possible with this design to obtain comparable levels of overall type I error and power by using about half the sample for stage I and carrying about 0.1% of SNPs forward to the second stage, the optimal design depending primarily upon the ratio of costs per genotype for stages I and II. However, with the rapidly declining costs of the commercial panels, the generally low observed ORs of current studies, and many studies aiming to test multiple hypotheses and multiple endpoints, many investigators are abandoning the two-stage design in favor of simply genotyping all available subjects using a standard high-density panel. Concern is sometimes raised about the absence of a ``replication'' panel in this approach, as required by some high-profile journals, but it must be appreciated that the two-stage design is not a discovery/replication design but simply a more efficient design for discovery using a joint analysis of the data from both stages. Once a subset of highly-significant associations has been discovered, a truly independent ``exact replication'' study is needed in a similar population of the same promising SNPs using similar methods.Comment: Published in at http://dx.doi.org/10.1214/09-STS288 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

A MMT/Hectospec Redshift Survey of 24 Micron Sources in the Spitzer First Look Survey

We present a spectroscopic survey using the MMT/Hectospec fiber spectrograph of 24 micron sources selected with the Spitzer Space Telescope in the Spitzer First Look Survey. We report 1296 new redshifts for 24 micron sources, including 599 with f(24micron) > 1 mJy. Combined with 291 additional redshifts for sources from the Sloan Digital Sky Survey (SDSS), our observing program was highly efficient and is ~90% complete for i' 1 mJy, and is 35% complete for i' < 20.5 mag and 0.3 mJy < f(24micron) < 1 mJy. Our Hectospec survey includes 1078 and 168 objects spectroscopically classified as galaxies and QSOs, respectively. Combining the Hectospec and SDSS samples, we find 24 micron-selected galaxies to z < 0.98 and QSOs to z < 3.6, with mean redshifts of = 0.27 and =1.1. As part of this publication, we include the redshift catalogs and the reduced spectra; these are also available online (http://mips.as.arizona.edu/~papovich/fls) and through the NASA/IPAC Infrared Science Archive (http://irsa.ipac.caltech.edu).Comment: Accepted for publication in the Astronomical Journal, AASTEX format, 23 pages, 7 figures (some in color). This replacement is the accepted version, and includes minor changes from previous version. Data tables and spectra available at http://mips.as.arizona.edu/~papovich/fls or at http://irsa.ipac.caltech.ed

Preferential Accumulation of Antigen-specific Effector CD4 T Cells at an Antigen Injection Site Involves CD62E-dependent Migration but Not Local Proliferation

The migration of antigen-specific T cells to nonlymphoid tissues is thought to be important for the elimination of foreign antigens from the body. However, recent results showing the migration of activated T cells into many nonlymphoid tissues raised the possibility that antigen-specific T cells do not migrate preferentially to nonlymphoid tissues containing antigen. We addressed this question by tracking antigen-specific CD4 T cells in the whole body after a localized subcutaneous antigen injection. Antigen-specific CD4 T cells proliferated in the skin-draining lymph nodes and the cells that underwent the most cell divisions acquired the ability to bind to CD62P. As time passed, CD62P-binding antigen-specific CD4 T cells with interferon γ production potential accumulated preferentially at the site of antigen injection but only in recipients that expressed CD62E. Surprisingly, these T cells did not proliferate in the injection site despite showing evidence of more cell divisions than the T cells in the draining lymph nodes. The results suggest that the most divided effector CD4 T cells from the lymph nodes enter the site of antigen deposition via recognition of CD62E on blood vessels and are retained there in a nonproliferative state via recognition of peptide–major histocompatibility complex II molecules

Spitzer infrared spectrometer 16μm observations of the GOODS fields

We present Spitzer 16μm imaging of the Great Observatories Origins Deep Survey (GOODS) fields. We survey 150 arcmin^2 in each of the two GOODS fields (North and South), to an average 3σ depth of 40 and 65 μJy, respectively. We detect ~1300 sources in both fields combined. We validate the photometry using the 3–24μm spectral energy distribution of stars in the fields compared to Spitzer spectroscopic templates. Comparison with ISOCAM and AKARI observations in the same fields shows reasonable agreement, though the uncertainties are large. We provide a catalog of photometry, with sources cross-correlated with available Spitzer, Chandra, and Hubble Space Telescope data. Galaxy number counts show good agreement with previous results from ISOCAM and AKARI with improved uncertainties. We examine the 16–24μm flux ratio and find that for most sources it lies within the expected locus for starbursts and infrared luminous galaxies. A color cut of S_(16)/S_(24) > 1.4 selects mostly sources which lie at 1.1 < z < 1.6, where the 24μm passband contains both the redshifted 9.7 μm silicate absorption and the minimum between polycyclic aromatic hydrocarbon emission peaks. We measure the integrated galaxy light of 16μm sources and find a lower limit on the galaxy contribution to the extragalactic background light at this wavelength to be 2.2 ± 0.2 nW m^(−2) sr^(−1)

Spectral Energy Distributions and Multiwavelength Selection of Type 1 Quasars

We present an analysis of the mid-infrared (MIR) and optical properties of type 1 (broad-line) quasars detected by the Spitzer Space Telescope. The MIR color-redshift relation is characterized to z ~ 3, with predictions to z = 7. We demonstrate how combining MIR and optical colors can yield even more efficient selection of active galactic nuclei (AGNs) than MIR or optical colors alone. Composite spectral energy distributions (SEDs) are constructed for 259 quasars with both Sloan Digital Sky Survey and Spitzer photometry, supplemented by near-IR, GALEX, VLA, and ROSAT data, where available. We discuss how the spectral diversity of quasars influences the determination of bolometric luminosities and accretion rates; assuming the mean SED can lead to errors as large as 50% for individual quasars when inferring a bolometric luminosity from an optical luminosity. Finally, we show that careful consideration of the shape of the mean quasar SED and its redshift dependence leads to a lower estimate of the fraction of reddened/obscured AGNs missed by optical surveys as compared to estimates derived from a single mean MIR to optical flux ratio

Morphologies and Spectral Energy Distributions of Extremely Red Galaxies in the GOODS-South Field

Using U'- through Ks-band imaging data in the GOODS-South field, we construct a large, complete sample of 275 ``extremely red objects'' (EROs; K_s<22.0, R-K_s>3.35; AB), all with deep HST/ACS imaging in B_435, V_606, i_775, and z_850, and well-calibrated photometric redshifts. Quantitative concentration and asymmetry measurements fail to separate EROs into distinct morphological classes. We therefore visually classify the morphologies of all EROs into four broad types: ``Early'' (elliptical-like), ``Late'' (disk galaxies), ``Irregular'' and ``Other'' (chain galaxies and low surface brightness galaxies), and calculate their relative fractions and comoving space densities. For a broad range of limiting magnitudes and color thresholds, the relative number of early-type EROs is approximately constant at 33-44%, and the comoving space densities of Early- and Late-type EROs are comparable. Mean rest-frame spectral energy distributions (SEDs) at wavelengths between 0.1 and 1.2 um are constructed for all EROs. The SEDs are extremely similar in their range of shapes, independent of morphological type. The implication is that any differences between the broad-band SEDs of Early-type EROs and the other types are relatively subtle, and there is no robust way of photometrically distinguishing between different morphological types with usual optical/near-infrared photometry.Comment: Submitted to the ApJL. A version with full-resolution figures, all GOODS data and all GOODS collaboration papers may be found at http://www.stsci.edu/science/goods

Hubble Ultra Deep Field-JD2: Mid-Infrared Evidence for a z ~ 2 Luminous Infrared Galaxy

The Hubble Ultra Deep Field source JD2 presented in Mobasher et al. is an unusual galaxy that is very faint at all wavelengths shortward of 1.1 μm. Photometric redshift fits to data between 0.4 and 8 μm yield a significant probability that it is an extremely massive galaxy at z ~ 6.5. In this paper we present new photometry at 16 and 22 μm from Spitzer Infrared Spectrograph (IRS) peak-up imaging of the Great Observatories Origins Deep Survey (GOODS) fields. We find that the spectral energy distribution shows a factor of ~4 rise in flux density between the 16 and 22 μm bandpass, which is most likely due to the entrance of polycyclic aromatic hydrocarbon emission features into the 22 and 24 μm passbands. The flux ratio between these bandpasses can be best fit by a z = 1.7 luminous infrared galaxy with a bolometric luminosity of (2-6) × 10^(11) L_⊙ corresponding to a star formation rate of 80 M_⊙ yr^(-1). The predicted flux density values at other longer wavelengths are below the detection limits of current instrumentation, but such sources could potentially be detected in lensed submillimeter surveys. Reevaluation of the optical/near-infrared photometry continues to favor z > 6 photometric redshift solutions, but we argue that the consistency of the multiwavelength parameters of this galaxy with other dusty starbursts favor the z ~ 2 mid-infrared photometric redshift. The data presented here provide evidence that optically undetected near-infrared sources that are detected at 24 μm are most likely dusty, starburst galaxies at a redshift of z ~ 2 with stellar masses >10^(10) M_⊙

Beyond Spheroids and Discs: Classifications of CANDELS Galaxy Structure at 1.4 < z < 2 via Principal Component Analysis

Important but rare and subtle processes driving galaxy morphology and star-formation may be missed by traditional spiral, elliptical, irregular or S\'ersic bulge/disk classifications. To overcome this limitation, we use a principal component analysis of non-parametric morphological indicators (concentration, asymmetry, Gini coefficient, $M_{20}$, multi-mode, intensity and deviation) measured at rest-frame $B$-band (corresponding to HST/WFC3 F125W at 1.4 $10^{10} M_{\odot}$) galaxy morphologies. Principal component analysis (PCA) quantifies the correlations between these morphological indicators and determines the relative importance of each. The first three principal components (PCs) capture $\sim$75 per cent of the variance inherent to our sample. We interpret the first principal component (PC) as bulge strength, the second PC as dominated by concentration and the third PC as dominated by asymmetry. Both PC1 and PC2 correlate with the visual appearance of a central bulge and predict galaxy quiescence. PC1 is a better predictor of quenching than stellar mass, as as good as other structural indicators (S\'ersic-n or compactness). We divide the PCA results into groups using an agglomerative hierarchical clustering method. Unlike S\'ersic, this classification scheme separates compact galaxies from larger, smooth proto-elliptical systems, and star-forming disk-dominated clumpy galaxies from star-forming bulge-dominated asymmetric galaxies. Distinguishing between these galaxy structural types in a quantitative manner is an important step towards understanding the connections between morphology, galaxy assembly and star-formation.Comment: 31 pages, 24 figures, accepted for publication in MNRA