Modeling and visualizing uncertainty in gene expression clusters using Dirichlet process mixtures

Although the use of clustering methods has rapidly become one of the standard computational approaches in the literature of microarray gene expression data, little attention has been paid to uncertainty in the results obtained. Dirichlet process mixture (DPM) models provide a nonparametric Bayesian alternative to the bootstrap approach to modeling uncertainty in gene expression clustering. Most previously published applications of Bayesian model-based clustering methods have been to short time series data. In this paper, we present a case study of the application of nonparametric Bayesian clustering methods to the clustering of high-dimensional nontime series gene expression data using full Gaussian covariances. We use the probability that two genes belong to the same cluster in a DPM model as a measure of the similarity of these gene expression profiles. Conversely, this probability can be used to define a dissimilarity measure, which, for the purposes of visualization, can be input to one of the standard linkage algorithms used for hierarchical clustering. Biologically plausible results are obtained from the Rosetta compendium of expression profiles which extend previously published cluster analyses of this data

Discovering transcriptional modules by Bayesian data integration

Motivation: We present a method for directly inferring transcriptional modules (TMs) by integrating gene expression and transcription factor binding (ChIP-chip) data. Our model extends a hierarchical Dirichlet process mixture model to allow data fusion on a gene-by-gene basis. This encodes the intuition that co-expression and co-regulation are not necessarily equivalent and hence we do not expect all genes to group similarly in both datasets. In particular, it allows us to identify the subset of genes that share the same structure of transcriptional modules in both datasets. Results: We find that by working on a gene-by-gene basis, our model is able to extract clusters with greater functional coherence than existing methods. By combining gene expression and transcription factor binding (ChIP-chip) data in this way, we are better able to determine the groups of genes that are most likely to represent underlying TMs

Some doubts on the validity of the foreground Galactic contribution subtraction from microwave anisotropies

The Galactic foreground contamination in CMBR anisotropies, especially from the dust component, is not easily separable from the cosmological or extragalactic component. In this paper, some doubts will be raised concerning the validity of the methods used to date to remove Galactic dust emission in order to show that none of them achieves its goal. First, I review the recent bibliography on the topic and discuss critically the methods of foreground subtraction: the cross-correlation with templates, analysis assuming the spectral shape of the Galactic components, the "maximum entropy method", "internal linear combination", and "wavelet-based high resolution fitting of internal templates". Second, I analyse the galactic latitude dependence from WMAP data. The frequency dependence is discussed with the data in the available literature. The result is that all methods of subtracting the Galactic contamination are inaccurate. The galactic latitude dependence analysis or the frequency dependence of the anisotropies in the range 50-250 GHz put a constraint on the maximum Galactic contribution in the power spectrum to be less than a ~10% (68% C. L.) for a ~1 degree scale, and possibly higher for larger scales. The origin of most of the signal in the CMBR anisotropies is not Galactic. In any case, the subtraction of the Galaxy is not accurate enough to allow a "precision Cosmology"; other sources of contamination (extragalactic, solar system) are also present.Comment: 24 pages, 1 figure, accepted to be published in J. Astrophys. Ast

Hyperon production in proton-sulphur collisions at 200 GeV/c

The WA94 experiment uses the production of strange particles and antiparticles to investigate the properties of hot hadronic matter created in heavy--ion interactions. \PgL, \PagL, \PgXm\ and \PagXp\ particle yields and transverse mass spectra are presented for pS interactions. These results are compared with those from SS interactions. Our results are also compared with those from pW and SW interactions of the WA85 experiment

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

RNA-Seq of Human Neurons Derived from iPS Cells Reveals Candidate Long Non-Coding RNAs Involved in Neurogenesis and Neuropsychiatric Disorders

Genome-wide expression analysis using next generation sequencing (RNA-Seq) provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs) provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Search for lepton-flavour-violating decays of the Higgs and Z bosons with the ATLAS detector

Direct searches for lepton flavour violation in decays of the Higgs and Z bosons with the ATLAS detector at the LHC are presented. The following three decays are considered: H→eτ, H→μτ, and Z→μτ. The searches are based on the data sample of proton–proton collisions collected by the ATLAS detector corresponding to an integrated luminosity of 20.3 fb−1 at a centre-of-mass energy of s√=8 TeV. No significant excess is observed, and upper limits on the lepton-flavour-violating branching ratios are set at the 95 % confidence level: Br (H→eτ)<1.04%, Br (H→μτ)<1.43%, and Br (Z→μτ)<1.69×10−5