AutoSOME: a clustering method for identifying gene expression modules without prior knowledge of cluster number

<p>Abstract</p> <p>Background</p> <p>Clustering the information content of large high-dimensional gene expression datasets has widespread application in "omics" biology. Unfortunately, the underlying structure of these natural datasets is often fuzzy, and the computational identification of data clusters generally requires knowledge about cluster number and geometry.</p> <p>Results</p> <p>We integrated strategies from machine learning, cartography, and graph theory into a new informatics method for automatically clustering self-organizing map ensembles of high-dimensional data. Our new method, called AutoSOME, readily identifies discrete and fuzzy data clusters without prior knowledge of cluster number or structure in diverse datasets including whole genome microarray data. Visualization of AutoSOME output using network diagrams and differential heat maps reveals unexpected variation among well-characterized cancer cell lines. Co-expression analysis of data from human embryonic and induced pluripotent stem cells using AutoSOME identifies >3400 up-regulated genes associated with pluripotency, and indicates that a recently identified protein-protein interaction network characterizing pluripotency was underestimated by a factor of four.</p> <p>Conclusions</p> <p>By effectively extracting important information from high-dimensional microarray data without prior knowledge or the need for data filtration, AutoSOME can yield systems-level insights from whole genome microarray expression studies. Due to its generality, this new method should also have practical utility for a variety of data-intensive applications, including the results of deep sequencing experiments. AutoSOME is available for download at <url>http://jimcooperlab.mcdb.ucsb.edu/autosome</url>.</p

The Origin of Double-peaked Narrow Lines in Active Galactic Nuclei. IV. Association with Galaxy Mergers

Double-peaked narrow emission lines in active galactic nucleus (AGN) spectra can be produced by AGN outflows, rotation, or dual AGNs, which are AGN pairs in ongoing galaxy mergers. Consequently, double-peaked narrow AGN emission lines are useful tracers of the coevolution of galaxies and their supermassive black holes, as driven by AGN feedback and AGN fueling. We investigate this concept further with follow-up optical longslit observations of a sample of 95 Sloan Digital Sky Survey (SDSS) galaxies that have double-peaked narrow AGN emission lines. Based on a kinematic analysis of the longslit spectra, we confirm previous work that finds that the majority of double-peaked narrow AGN emission lines are associated with outflows. We also find that eight of the galaxies have companion galaxies with line-of-sight velocity separations < 500 km/s and physical separations <30 kpc. Since we find evidence of AGNs in both galaxies, all eight of these systems are compelling dual AGN candidates. Galaxies with double-peaked narrow AGN emission lines occur in such galaxy mergers at least twice as often as typical active galaxies. Finally, we conclude that at least 3% of SDSS galaxies with double-peaked narrow AGN emission lines are found in galaxy mergers where both galaxies are resolved in SDSS imaging.Comment: 14 pages, 2 figures, ApJ in pres

The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells.

Lentiviral vectors designed for the treatment of the hemoglobinopathies require the inclusion of regulatory and strong enhancer elements to achieve sufficient expression of the β-globin transgene. Despite the inclusion of these elements, the efficacy of these vectors may be limited by transgene silencing due to the genomic environment surrounding the integration site. Barrier insulators can be used to give more consistent expression and resist silencing even with lower vector copies. Here, the barrier activity of an insulator element from the human ankyrin-1 gene was analyzed in a lentiviral vector carrying an antisickling human β-globin gene. Inclusion of a single copy of the Ankyrin insulator did not affect viral titer, and improved the consistency of expression from the vector in murine erythroleukemia cells. The presence of the Ankyrin insulator element did not change transgene expression in human hematopoietic cells in short-term erythroid culture or in vivo in primary murine transplants. However, analysis in secondary recipients showed that the lentiviral vector with the Ankyrin element preserved transgene expression, whereas expression from the vector lacking the Ankyrin insulator decreased in secondary recipients. These studies demonstrate that the Ankyrin insulator may improve long-term β-globin expression in hematopoietic stem cells for gene therapy of hemoglobinopathies

The DEEP3 Galaxy Redshift Survey: The Impact of Environment on the Size Evolution of Massive Early-type Galaxies at Intermediate Redshift

Using data drawn from the DEEP2 and DEEP3 Galaxy Redshift Surveys, we investigate the relationship between the environment and the structure of galaxies residing on the red sequence at intermediate redshift. Within the massive (10 < log(M*/Msun) < 11) early-type population at 0.4 < z <1.2, we find a significant correlation between local galaxy overdensity (or environment) and galaxy size, such that early-type systems in higher-density regions tend to have larger effective radii (by ~0.5 kpc or 25% larger) than their counterparts of equal stellar mass and Sersic index in lower-density environments. This observed size-density relation is consistent with a model of galaxy formation in which the evolution of early-type systems at z < 2 is accelerated in high-density environments such as groups and clusters and in which dry, minor mergers (versus mechanisms such as quasar feedback) play a central role in the structural evolution of the massive, early-type galaxy population.Comment: 11 pages, 5 figures, 2 tables; resubmitted to MNRAS after addressing referee's comments (originally submitted to journal on August 16, 2011

Dependence of Galaxy Quenching on Halo Mass and Distance from its Centre

We study the dependence of star-formation quenching on galaxy mass and environment, in the SDSS (z~0.1) and the AEGIS (z~1). It is crucial that we define quenching by low star-formation rate rather than by red colour, given that one third of the red galaxies are star forming. We address stellar mass M*, halo mass Mh, density over the nearest N neighbours deltaN, and distance to the halo centre D. The fraction of quenched galaxies appears more strongly correlated with Mh at fixed M* than with M* at fixed Mh, while for satellites quenching also depends on D. We present the M*-Mh relation for centrals at z~1. At z~1, the dependence of quenching on M* at fixed Mh is somewhat more pronounced than at z~0, but the quenched fraction is low (10%) and the haloes are less massive. For satellites, M*-dependent quenching is noticeable at high D, suggesting a quenching dependence on sub-halo mass for recently captured satellites. At small D, where satellites likely fell in more than a few Gyr ago, quenching strongly depends on Mh, and not on M*. The Mh-dependence of quenching is consistent with theoretical wisdom where virial shock heating in massive haloes shuts down accretion and triggers ram-pressure stripping, causing quenching. The interpretation of deltaN is complicated by the fact that it depends on the number of observed group members compared to N, motivating the use of D as a better measure of local environment.Comment: 23 pages, 13 figures, accepted by MNRA

On the Evolution of the Velocity-Mass-Size Relations of Disk-Dominated Galaxies over the Past 10 Billion Years

We study the evolution of the scaling relations between maximum circular velocity, stellar mass and optical half-light radius of star-forming disk-dominated galaxies in the context of LCDM-based galaxy formation models. Using data from the literature combined with new data from the DEEP2 and AEGIS surveys we show that there is a consistent observational and theoretical picture for the evolution of these scaling relations from z\sim 2 to z=0. The evolution of the observed stellar scaling relations is weaker than that of the virial scaling relations of dark matter haloes, which can be reproduced, both qualitatively and quantitatively, with a simple, cosmologically-motivated model for disk evolution inside growing NFW dark matter haloes. In this model optical half-light radii are smaller, both at fixed stellar mass and maximum circular velocity, at higher redshifts. This model also predicts that the scaling relations between baryonic quantities evolve even more weakly than the corresponding stellar relations. We emphasize, though, that this weak evolution does not imply that individual galaxies evolve weakly. On the contrary, individual galaxies grow strongly in mass, size and velocity, but in such a way that they move largely along the scaling relations. Finally, recent observations have claimed surprisingly large sizes for a number of star-forming disk galaxies at z \sim 2, which has caused some authors to suggest that high redshift disk galaxies have abnormally high spin parameters. However, we argue that the disk scale lengths in question have been systematically overestimated by a factor \sim 2, and that there is an offset of a factor \sim 1.4 between H\alpha sizes and optical sizes. Taking these effects into account, there is no indication that star forming galaxies at high redshifts (z\sim 2) have abnormally high spin parameters.Comment: 19 pages, 10 figures, accepted to MNRAS, minor changes to previous versio

What did HERA teach us about the structure of the proton?

Starting in 2008 the H1 and ZEUS experiments have been combining their data in order to provide the most complete and accurate set of deep-inelastic data as the legacy of HERA. The present review presents these combinations, both published and preliminary, and explores how they have been used to give information on the structure of the proton. The HERAPDF parton distribution functions (PDFs) are presented and compared with other current PDFs and with data from the Tevatron and LHC colliders.Comment: 49 pages, 49 figures, to be published in J.Phys.

Instrument-assisted Soft Tissue Mobilization: Effects on the Properties of Human Plantar Flexors

The effect of instrument-assisted soft tissue mobilization (ISTM) on passive properties and inflammation in human skeletal muscle has not been evaluated. Passive properties of muscle, inflammatory myokines and subjective reporting of functional ability were used to identify the effects of ISTM on the plantar flexors. 11 healthy men were measured for passive musculotendinous stiffness (MTS), passive range of motion (PROM), passive resistive torque (PASTQ) and maximum voluntary contraction peak torque (MVCPT) for plantar flexor muscles of the lower leg. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured from muscle biopsies from the gastrocnemius, and subjective measurements of functional ability were taken using the perception of functional ability questionnaire (PFAQ). MTS, PROM, PRT and MVCPT were measured in the treatment leg (TL) and control leg (CL) before, immediately after, 24 h, 48 h and 72 h following IASTM. Biopsies for IL-6 and TNF-α and PFAQ responses were collected before as well as 24 h, 48 h and 72 h after IASTM. There were no significant differences in MTS, PROM, PASTQ, MVCPT, IL-6 and TNF-α between the TL or CL. A significant decrease in the perception of function and a significant increase in pain for the TL were found following IASTM