Asterias: a parallelized web-based suite for the analysis of expression and aCGH data

Asterias (\url{http://www.asterias.info}) is an integrated collection of freely-accessible web tools for the analysis of gene expression and aCGH data. Most of the tools use parallel computing (via MPI). Most of our applications allow the user to obtain additional information for user-selected genes by using clickable links in tables and/or figures. Our tools include: normalization of expression and aCGH data; converting between different types of gene/clone and protein identifiers; filtering and imputation; finding differentially expressed genes related to patient class and survival data; searching for models of class prediction; using random forests to search for minimal models for class prediction or for large subsets of genes with predictive capacity; searching for molecular signatures and predictive genes with survival data; detecting regions of genomic DNA gain or loss. The capability to send results between different applications, access to additional functional information, and parallelized computation make our suite unique and exploit features only available to web-based applications.Comment: web based application; 3 figure

Asterias: integrated analysis of expression and aCGH data using an open-source, web-based, parallelized software suite

Asterias (http://www.asterias.info) is an open-source, web-based, suite for the analysis of gene expression and aCGH data. Asterias implements validated statistical methods, and most of the applications use parallel computing, which permits taking advantage of multicore CPUs and computing clusters. Access to, and further analysis of, additional biological information and annotations (PubMed references, Gene Ontology terms, KEGG and Reactome pathways) are available either for individual genes (from clickable links in tables and figures) or sets of genes. These applications cover from array normalization to imputation and preprocessing, differential gene expression analysis, class and survival prediction and aCGH analysis. The source code is available, allowing for extention and reuse of the software. The links and analysis of additional functional information, parallelization of computation and open-source availability of the code make Asterias a unique suite that can exploit features specific to web-based environments

Coagulation factor VIIa binds to herpes simplex virus 1‐encoded glycoprotein C forming a factor X‐enhanced tenase complex oriented on membranes

BackgroundThe cell membrane‐derived initiators of coagulation, tissue factor (TF) and anionic phospholipid (aPL), are constitutive on the herpes simplex virus type 1 (HSV1) surface, bypassing physiological regulation. TF and aPL accelerate proteolytic activation of factor (F) X to FXa by FVIIa to induce clot formation and cell signaling. Thus, infection in vivo is enhanced by virus surface TF. HSV1‐encoded glycoprotein C (gC) is implicated in this tenase activity by providing viral FX binding sites and increasing FVIIa function in solution.ObjectiveTo examine the biochemical influences of gC on FVIIa‐dependent FX activation.MethodsImmunogold electron microscopy (IEM), kinetic chromogenic assays and microscale thermophoresis were used to dissect tenase biochemistry. Recombinant TF and gC were solubilized (s) by substituting the transmembrane domain with poly‐histidine, which could be orientated on synthetic unilamellar vesicles containing Ni‐chelating lipid (Ni‐aPL). These constructs were compared to purified HSV1 TF±/gC ± variants.ResultsIEM confirmed that gC, TF, and aPL are simultaneously expressed on a single HSV1 particle where the contribution of gC to tenase activity required the availability of viral TF. Unlike viral tenase activity, the cofactor effects of sTF and sgC on FVIIa was additive when bound to Ni‐aPL. FVIIa was found to bind to sgC and this was enhanced by FX. Orientation of sgC on a lipid membrane was critical for FVIIa‐dependent FX activation.ConclusionsThe assembly of gC with FVIIa/FX parallels that of TF and may involve other constituents on the HSV1 envelope with implications in virus infection and pathology.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155933/1/jth14790-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155933/2/jth14790.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155933/3/jth14790_am.pd

Asterias: A Parallelized Web-based Suite for the Analysis of Expression and aCGH Data

The analysis of expression and CGH arrays plays a central role in the study of complex diseases, especially cancer, including finding markers for early diagnosis and prognosis, choosing an optimal therapy, or increasing our understanding of cancer development and metastasis. Asterias (http://www.asterias.info) is an integrated collection of freely-accessible web tools for the analysis of gene expression and aCGH data. Most of the tools use parallel computing (via MPI) and run on a server with 60 CPUs for computation; compared to a desktop or server-based but not parallelized application, parallelization provides speed ups of factors up to 50. Most of our applications allow the user to obtain additional information for user-selected genes (chromosomal location, PubMed ids, Gene Ontology terms, etc.) by using clickable links in tables and/or figures. Our tools include: normalization of expression and aCGH data (DNMAD); converting between different types of gene/clone and protein identifiers (IDconverter/IDClight); filtering and imputation (preP); finding differentially expressed genes related to patient class and survival data (Pomelo II); searching for models of class prediction (Tnasas); using random forests to search for minimal models for class prediction or for large subsets of genes with predictive capacity (GeneSrF); searching for molecular signatures and predictive genes with survival data (SignS); detecting regions of genomic DNA gain or loss (ADaCGH). The capability to send results between different applications, access to additional functional information, and parallelized computation make our suite unique and exploit features only available to web-based applications

A panchromatic study of BLAST counterparts: total star-formation rate, morphology, AGN fraction and stellar mass

We carry out a multi-wavelength study of individual galaxies detected by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST) and identified at other wavelengths, using data spanning the radio to the ultraviolet (UV). We develop a Monte Carlo method to account for flux boosting, source blending, and correlations among bands, which we use to derive deboosted far-infrared (FIR) luminosities for our sample. We estimate total star-formation rates for BLAST counterparts with z < 0.9 by combining their FIR and UV luminosities. Star formation is heavily obscured at L_FIR > 10^11 L_sun, z > 0.5, but the contribution from unobscured starlight cannot be neglected at L_FIR < 10^11 L_sun, z < 0.25. We assess that about 20% of the galaxies in our sample show indication of a type-1 active galactic nucleus (AGN), but their submillimeter emission is mainly due to star formation in the host galaxy. We compute stellar masses for a subset of 92 BLAST counterparts; these are relatively massive objects, with a median mass of ~10^11 M_sun, which seem to link the 24um and SCUBA populations, in terms of both stellar mass and star-formation activity. The bulk of the BLAST counterparts at z<1 appear to be run-of-the-mill star-forming galaxies, typically spiral in shape, with intermediate stellar masses and practically constant specific star-formation rates. On the other hand, the high-z tail of the BLAST counterparts significantly overlaps with the SCUBA population, in terms of both star-formation rates and stellar masses, with observed trends of specific star-formation rate that support strong evolution and downsizing.Comment: Accepted for publication in the Astrophysical Journal. 44 pages, 11 figures. The SED template for the derivation of L_FIR has changed (added new figure) and the discussion on the stellar masses has been improved. The complete set of full-color postage-stamps can be found at http://blastexperiment.info/results_images/moncelsi

Spatiotemporal regulation of clonogenicity in colorectal cancer xenografts

Cancer evolution is predominantly studied by focusing on differences in the genetic characteristics of malignant cells within tumors. However, the spatiotemporal dynamics of clonal outgrowth that underlie evolutionary trajectories remain largely unresolved. Here, we sought to unravel the clonal dynamics of colorectal cancer (CRC) expansion in space and time by using a color-based clonal tracing method. This method involves lentiviral red-green-blue (RGB) marking of cell populations, which enabled us to track individual cells and their clonal outgrowth during tumor initiation and growth in a xenograft model. We found that clonal expansion largely depends on the location of a clone, as small clones reside in the center and large clones mostly drive tumor growth at the border. These dynamics are recapitulated in a computational model, which confirms that the clone position within a tumor rather than cell-intrinsic features, is crucial for clonal outgrowth. We also found that no significant clonal loss occurs during tumor growth and clonal dispersal is limited in most models. Our results imply that, in addition to molecular features of clones such as (epi-)genetic differences between cells, clone location and the geometry of tumor growth are crucial for clonal expansion. Our findings suggest that either microenvironmental signals on the tumor border or differences in physical properties within the tumor, are major contributors to explain heterogeneous clonal expansion. Thus, this study provides further insights into the dynamics of solid tumor growth and progression, as well as the origins of tumor cell heterogeneity in a relevant model system

Maternal Fish Consumption and Infant Birth Size and Gestation: New York State Angler Cohort Study

BACKGROUND: The scientific literature poses a perplexing dilemma for pregnant women with respect to the consumption of fish from natural bodies of water. On one hand, fish is a good source of protein, low in fat and a rich source of other nutrients all of which have presumably beneficial effects on developing embryos and fetuses. On the other hand, consumption of fish contaminated with environmental toxicants such as polychlorinated biphenyls (PCBs) has been associated with decrements in gestation and birth size. METHODS: 2,716 infants born between 1986–1991 to participants of the New York State Angler Cohort Study were studied with respect to duration of maternal consumption of contaminated fish from Lake Ontario and its tributaries and gestation and birth size. Hospital delivery records (maternal and newborn) were obtained for 92% of infants for the ascertainment of gestation (weeks), birth size (weight, length, chest, and head circumference) and other known determinants of fetal growth (i.e., maternal parity, history of placental infarction, uterine bleeding, pregnancy loss or cigarette smoking and infant's race, sex and presence of birth defect). Duration of maternal fish consumption prior to the index infant's birth was categorized as: none; 1–2, 3–7, 8+ years, while birth weight (in grams), birth length (in centimeters), and head and chest circumference (in centimeters) were left as continuous variables in multiple linear regression models. Birth size percentiles, ponderal indices and head to chest circumference ratios were computed to further assess proportionality and birth size in relation to gestational age. RESULTS: Analysis of variance failed to identify significant mean differences in gestation or any measure of birth size in relation to duration of maternal lifetime fish consumption. Multiple linear regressions identified gestational age, male sex, number of daily cigarettes, parity and placental infarction, as significant determinants of birth size. CONCLUSIONS: The results support the absence of an adverse relation between Lake Ontario fish consumption and reduced birth size as measured by weight, length and head circumference. Biological determinants and maternal cigarette smoking during pregnancy remain important determinants of birth size