Expression profiling of human renal carcinomas with functional taxonomic analysis

BACKGROUND: Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. RESULTS: We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors) and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p < 0.001) gene expression changes in clear cell renal carcinomas compared to normal kidney. These genes were classified with a tool to conceptualize expression patterns called "Functional Taxonomy". Each tumor type had a distinct "signature," with a high number of genes in the categories of Metabolism, Signal Transduction, and Cellular and Matrix Organization and Adhesion. CONCLUSIONS: Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data

CoAIMs: A Cost-Effective Panel of Ancestry Informative Markers for Determining Continental Origins

Genetic ancestry is known to impact outcomes of genotype-phenotype studies that are designed to identify risk for common diseases in human populations. Failure to control for population stratification due to genetic ancestry can significantly confound results of disease association studies. Moreover, ancestry is a critical factor in assessing lifetime risk of disease, and can play an important role in optimizing treatment. As modern medicine moves towards using personal genetic information for clinical applications, it is important to determine genetic ancestry in an accurate, cost-effective and efficient manner. Self-identified race is a common method used to track and control for population stratification; however, social constructs of race are not necessarily informative for genetic applications. The use of ancestry informative markers (AIMs) is a more accurate method for determining genetic ancestry for the purposes of population stratification.Here we introduce a novel panel of 36 microsatellite (MSAT) AIMs that determines continental admixture proportions. This panel, which we have named Continental Ancestry Informative Markers or CoAIMs, consists of MSAT AIMs that were chosen based upon their measure of genetic variance (F(st)), allele frequencies and their suitability for efficient genotyping. Genotype analysis using CoAIMs along with a Bayesian clustering method (STRUCTURE) is able to discern continental origins including Europe/Middle East (Caucasians), East Asia, Africa, Native America, and Oceania. In addition to determining continental ancestry for individuals without significant admixture, we applied CoAIMs to ascertain admixture proportions of individuals of self declared race.CoAIMs can be used to efficiently and effectively determine continental admixture proportions in a sample set. The CoAIMs panel is a valuable resource for genetic researchers performing case-control genetic association studies, as it can control for the confounding effects of population stratification. The MSAT-based approach used here has potential for broad applicability as a cost effective tool toward determining admixture proportions

Tracing PAHs and Warm Dust Emission in the Seyfert Galaxy NGC 1068

We present a study of the nearby Seyfert galaxy NGC 1068 using mid- and far- infrared data acquired with the IRAC, IRS, and MIPS instruments aboard the Spitzer Space Telescope. The images show extensive 8 um and 24 um emission coinciding with star formation in the inner spiral approximately 15" (1 kpc) from the nucleus, and a bright complex of star formation 47" (3 kpc) SW of the nucleus. The brightest 8 um PAH emission regions coincide remarkably well with knots observed in an Halpha image. Strong PAH features at 6.2, 7.7, 8.6, and 11.3 um are detected in IRS spectra measured at numerous locations inside, within, and outside the inner spiral. The IRAC colors and IRS spectra of these regions rule out dust heated by the AGN as the primary emission source; the SEDs are dominated by starlight and PAH emission. The equivalent widths and flux ratios of the PAH features in the inner spiral are generally consistent with conditions in a typical spiral galaxy ISM. Interior to the inner spiral, the influence of the AGN on the ISM is evident via PAH flux ratios indicative of a higher ionization parameter and a significantly smaller mean equivalent width than observed in the inner spiral. The brightest 8 and 24 um emission peaks in the disk of the galaxy, even at distances beyond the inner spiral, are located within the ionization cones traced by [O III]/Hbeta, and they are also remarkably well aligned with the axis of the radio jets. Although it is possible that radiation from the AGN may directly enhance PAH excitation or trigger the formation of OB stars that subsequently excite PAH emission at these locations in the inner spiral, the orientation of collimated radiation from the AGN and star formation knots in the inner spiral could be coincidental. (abridged)Comment: 20 pages, 11 figures; AJ, accepted; full resolution version available at http://spider.ipac.caltech.edu/staff/jhhowell/astro/howelln1068.pd

GAMA: towards a physical understanding of galaxy formation

The Galaxy And Mass Assembly (GAMA) project is the latest in a tradition of large galaxy redshift surveys, and is now underway on the 3.9m Anglo-Australian Telescope at Siding Spring Observatory. GAMA is designed to map extragalactic structures on scales of 1kpc - 1Mpc in complete detail to a redshift of z~0.2, and to trace the distribution of luminous galaxies out to z~0.5. The principal science aim is to test the standard hierarchical structure formation paradigm of Cold Dark Matter (CDM) on scales of galaxy groups, pairs, discs, bulges and bars. We will measure (1) the Dark Matter Halo Mass Function (as inferred from galaxy group velocity dispersions); (2) baryonic processes, such as star formation and galaxy formation efficiency (as derived from Galaxy Stellar Mass Functions); and (3) the evolution of galaxy merger rates (via galaxy close pairs and galaxy asymmetries). Additionally, GAMA will form the central part of a new galaxy database, which aims to contain 275,000 galaxies with multi-wavelength coverage from coordinated observations with the latest international ground- and space-based facilities: GALEX, VST, VISTA, WISE, HERSCHEL, GMRT and ASKAP. Together, these data will provide increased depth (over 2 magnitudes), doubled spatial resolution (0.7"), and significantly extended wavelength coverage (UV through Far-IR to radio) over the main SDSS spectroscopic survey for five regions, each of around 50 deg^2. This database will permit detailed investigations of the structural, chemical, and dynamical properties of all galaxy types, across all environments, and over a 5 billion year timeline.Comment: GAMA overview which appeared in the October 2009 issue of Astronomy & Geophysics, ref: Astron.Geophys. 50 (2009) 5.1

Galaxy and Mass Assembly: FUV, NUV, ugrizYJHK Petrosian, Kron and Sérsic photometry

In order to generate credible 0.1-2 μm spectral energy distributions, the Galaxy and Mass Assembly (GAMA) project requires many gigabytes of imaging data from a number of instruments to be reprocessed into a standard format. In this paper, we discuss the software infrastructure we use, and create self-consistent ugrizYJHK photometry for all sources within the GAMA sample. Using UKIDSS and SDSS archive data, we outline the pre-processing necessary to standardize all images to a common zero-point, the steps taken to correct for the seeing bias across the data set and the creation of gigapixel-scale mosaics of the three 4 × 12 deg2 GAMA regions in each filter. From these mosaics, we extract source catalogues for the GAMA regions using elliptical Kron and Petrosian matched apertures. We also calculate Sérsic magnitudes for all galaxies within the GAMA sample using sigma, a galaxy component modelling wrapper for galfit 3. We compare the resultant photometry directly and also calculate the r-band galaxy luminosity function for all photometric data sets to highlight the uncertainty introduced by the photometric method. We find that (1) changing the object detection threshold has a minor effect on the best-fitting Schechter parameters of the overall population (M*± 0.055 mag, α± 0.014, ϕ*± 0.0005 h3 Mpc−3); (2) there is an offset between data sets that use Kron or Petrosian photometry, regardless of the filter; (3) the decision to use circular or elliptical apertures causes an offset in M* of 0.20 mag; (4) the best-fitting Schechter parameters from total-magnitude photometric systems (such as SDSS modelmag or Sérsic magnitudes) have a steeper faint-end slope than photometric systems based upon Kron or Petrosian measurements; and (5) our Universe's total luminosity density, when calculated using Kron or Petrosian r-band photometry, is underestimated by at least 15 per cen

SMHASH:A new mid-infrared RR Lyrae distance determination for the Local Group dwarf spheroidal galaxy Sculptor

We present a new distance estimation for the Milky Way dwarf spheroidal satellite Sculptor obtained from multi-epoch mid-infrared observations of RR Lyrae stars. The 3.6 {\mu}m observations have been acquired with the Infrared Array Camera on board the Spitzer Space Telescope as part of the SMHASH Program. Mid-infrared light curves for 42 RRL were obtained, from which we measured Sculptor's distance modulus to be {\mu} = 19.60 $\pm$ 0.02 (statistical) $\pm$ 0.04 (photometric) mag (with $\sigma_{sys}=$ = 0.09 mag), using the 3.6 {\mu}m empirical period-luminosity relations derived from the Galactic globular cluster M4, or {\mu} = 19.57 $\pm$ 0.02 (statistical) $\pm$ 0.04 (photometric) mag (with $\sigma_{sys}=$ = 0.11 mag) using empirical relations in the same passband recently derived from the Large Magellanic Cloud globular cluster Reticulum. Both these measurements are in good agreement with values presented in previous works with Sculptor RR Lyrae stars in optical bands, and are also consistent with recent near-infrared RR Lyrae results. Best agreement with the literature is found for the latter modulus which is equivalent to a distance of d = 82 $\pm$ 1 (statistical) $\pm$ 2 (photometric) kpc (with $\sigma_{sys}=$ = 4 kpc). Finally, using a subsample of RR Lyrae stars with spectroscopic metallicities, we demonstrate that these distance estimates are not affected by metallicity effects.Comment: 24 pages, 11 figures. Accepted for publication in MNRA

Galaxy And Mass Assembly (GAMA) : trends in galaxy colours, morphology, and stellar populations with large-scale structure, group, and pair environments

We explore trends in galaxy properties with Mpc-scale structures using catalogues of environment and large-scale structure from the Galaxy And Mass Assembly (GAMA) survey. Existing GAMA catalogues of large-scale structure, group, and pair membership allow us to construct galaxy stellar mass functions for different environmental types. To avoid simply extracting the known underlying correlations between galaxy properties and stellar mass, we create a mass matched sample of galaxies with stellar masses within 9.5 ≤ log M*/h−2 M⊙ ≤ 11 for each environmental population. Using these samples, we show that mass normalized galaxies in different large-scale environments have similar energy outputs, u − r colours, luminosities, and morphologies. Extending our analysis to group and pair environments, we show that galaxies that are not in groups or pairs exhibit similar characteristics to each other regardless of broader environment. For our mass controlled sample, we fail to see a strong dependence of Sérsic index or galaxy luminosity on halo mass, but do find that it correlates very strongly with colour. Repeating our analysis for galaxies that have not been mass controlled introduces and amplifies trends in the properties of galaxies in pairs, groups, and large-scale structure, indicating that stellar mass is the most important predictor of the galaxy properties we examine, as opposed to environmental classifications.Publisher PDFPeer reviewe

SMHASH: Anatomy of the Orphan Stream using RR Lyrae stars

Stellar tidal streams provide an opportunity to study the motion and structure of the disrupting galaxy as well as the gravitational potential of its host. Streams around the Milky Way are especially promising as phase space positions of individual stars will be measured by ongoing or upcoming surveys. Nevertheless, it remains a challenge to accurately assess distances to stars farther than 10 kpc from the Sun, where we have the poorest knowledge of the Galaxy's mass distribution. To address this we present observations of 32 candidate RR Lyrae stars in the Orphan tidal stream taken as part of the Spitzer Merger History and Shape of the Galactic Halo (SMHASH) program. The extremely tight correlation between the periods, luminosities, and metallicities of RR Lyrae variable stars in the Spitzer IRAC $\mathrm{3.6 \mu m}$ band allows the determination of precise distances to individual stars; the median statistical distance uncertainty to each RR Lyrae star is $2.5\%$. By fitting orbits in an example potential we obtain an upper limit on the mass of the Milky Way interior to 60 kpc of $\mathrm{5.6_{-1.1}^{+1.2}\times 10^{11}\ M_\odot}$, bringing estimates based on the Orphan Stream in line with those using other tracers. The SMHASH data also resolve the stream in line--of--sight depth, allowing a new perspective on the internal structure of the disrupted dwarf galaxy. Comparing with N--body models we find that the progenitor had an initial dark halo mass of approximately $\mathrm{3.2 \times 10^{9}\ M_\odot}$, placing the Orphan Stream's progenitor amongst the classical dwarf spheroidals

Galaxy And Mass Assembly (GAMA): trends in galaxy colours, morphology, and stellar populations with large-scale structure, group, and pair environments

We explore trends in galaxy properties with Mpc-scale structures using catalogues of environment and large-scale structure from the Galaxy And Mass Assembly (GAMA) survey. Existing GAMA catalogues of large-scale structure, group, and pair membership allow us to construct galaxy stellar mass functions for different environmental types. To avoid simply extracting the known underlying correlations between galaxy properties and stellar mass, we create a mass matched sample of galaxies with stellar masses within 9.5 ≤ log M*/h−2 M⊙ ≤ 11 for each environmental population. Using these samples, we show that mass normalized galaxies in different large-scale environments have similar energy outputs, u − r colours, luminosities, and morphologies. Extending our analysis to group and pair environments, we show that galaxies that are not in groups or pairs exhibit similar characteristics to each other regardless of broader environment. For our mass controlled sample, we fail to see a strong dependence of Sérsic index or galaxy luminosity on halo mass, but do find that it correlates very strongly with colour. Repeating our analysis for galaxies that have not been mass controlled introduces and amplifies trends in the properties of galaxies in pairs, groups, and large-scale structure, indicating that stellar mass is the most important predictor of the galaxy properties we examine, as opposed to environmental classifications

The influence of tumor size and environment on gene expression in commonly used human tumor lines

BACKGROUND: The expression profiles of solid tumor models in rodents have been only minimally studied despite their extensive use to develop anticancer agents. We have applied RNA expression profiling using Affymetrix U95A GeneChips to address fundamental biological questions about human tumor lines. METHODS: To determine whether gene expression changed significantly as a tumor increased in size, we analyzed samples from two human colon carcinoma lines (Colo205 and HCT-116) at three different sizes (200 mg, 500 mg and 1000 mg). To investigate whether gene expression was influenced by the strain of mouse, tumor samples isolated from C.B-17 SCID and Nu/Nu mice were also compared. Finally, the gene expression differences between tissue culture and in vivo samples were investigated by comparing profiles from lines grown in both environments. RESULTS: Multidimensional scaling and analysis of variance demonstrated that the tumor lines were dramatically different from each other and that gene expression remained constant as the tumors increased in size. Statistical analysis revealed that 63 genes were differentially expressed due to the strain of mouse the tumor was grown in but the function of the encoded proteins did not link to any distinct biological pathways. Hierarchical clustering of tissue culture and xenograft samples demonstrated that for each individual tumor line, the in vivo and in vitro profiles were more similar to each other than any other profile. We identified 36 genes with a pattern of high expression in xenograft samples that encoded proteins involved in extracellular matrix, cell surface receptors and transcription factors. An additional 17 genes were identified with a pattern of high expression in tissue culture samples and encoded proteins involved in cell division, cell cycle and RNA production. CONCLUSIONS: The environment a tumor line is grown in can have a significant effect on gene expression but tumor size has little or no effect for subcutaneously grown solid tumors. Furthermore, an individual tumor line has an RNA expression pattern that clearly defines it from other lines even when grown in different environments. This could be used as a quality control tool for preclinical oncology studies