Seeing the Forest for the Trees: Using the Gene Ontology to Restructure Hierarchical Clustering

Motivation: There is a growing interest in improving the cluster analysis of expression data by incorporating into it prior knowledge, such as the Gene Ontology (GO) annotations of genes, in order to improve the biological relevance of the clusters that are subjected to subsequent scrutiny. The structure of the GO is another source of background knowledge that can be exploited through the use of semantic similarity. Results: We propose here a novel algorithm that integrates semantic similarities (derived from the ontology structure) into the procedure of deriving clusters from the dendrogram constructed during expression-based hierarchical clustering. Our approach can handle the multiple annotations, from different levels of the GO hierarchy, which most genes have. Moreover, it treats annotated and unannotated genes in a uniform manner. Consequently, the clusters obtained by our algorithm are characterized by significantly enriched annotations. In both cross-validation tests and when using an external index such as protein–protein interactions, our algorithm performs better than previous approaches. When applied to human cancer expression data, our algorithm identifies, among others, clusters of genes related to immune response and glucose metabolism. These clusters are also supported by protein–protein interaction data. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.Lynne and William Frankel Center for Computer Science; Paul Ivanier center for robotics research and production; National Institutes of Health (R01 HG003367-01A1

Deformations of the Boson sp(4,R)sp(4,R) Representation and its Subalgebras

The boson representation of the sp(4,R) algebra and two distinct deformations of it, are considered, as well as the compact and noncompact subalgebras of each. The initial as well as the deformed representations act in the same Fock space. One of the deformed representation is based on the standard q-deformation of the boson creation and annihilation operators. The subalgebras of sp(4,R) (compact u(2) and three representations of the noncompact u(1,1) are also deformed and are contained in this deformed algebra. They are reducible in the action spaces of sp(4,R) and decompose into irreducible representations. The other deformed representation, is realized by means of a transformation of the q-deformed bosons into q-tensors (spinor-like) with respect to the standard deformed su(2). All of its generators are deformed and have expressions in terms of tensor products of spinor-like operators. In this case, an other deformation of su(2) appears in a natural way as a subalgebra and can be interpreted as a deformation of the angular momentum algebra so(3). Its representation is reducible and decomposes into irreducible ones that yields a complete description of the same

The Magnetic Electron Ion Spectrometer (MagEIS) Instruments Aboard the Radiation Belt Storm Probes (RBSP) Spacecraft

This paper describes the Magnetic Electron Ion Spectrometer (MagEIS) instruments aboard the RBSP spacecraft from an instrumentation and engineering point of view. There are four magnetic spectrometers aboard each of the two spacecraft, one low-energy unit (20–240 keV), two medium-energy units (80–1200 keV), and a high-energy unit (800–4800 keV). The high unit also contains a proton telescope (55 keV–20 MeV). The magnetic spectrometers focus electrons within a selected energy pass band upon a focal plane of several silicon detectors where pulse-height analysis is used to determine if the energy of the incident electron is appropriate for the electron momentum selected by the magnet. Thus each event is a two-parameter analysis, an approach leading to a greatly reduced background. The physics of these instruments are described in detail followed by the engineering implementation. The data outputs are described, and examples of the calibration results and early flight data presented

Magnetic states at the surface of alpha Fe2O3 thin films doped with Ti, Zn, or Sn

The spin states at the surface of epitaxial thin films of hematite, both undoped and doped with 1% Ti, Sn or Zn, respectively, were probed with x-ray magnetic linear dichroism (XMLD) spectroscopy. Morin transitions were observed for the undoped (T_M~200 K) and Sn-doped (T_M~300 K) cases, while Zn and Ti-doped samples were always in the high and low temperature phases, respectively. In contrast to what has been reported for bulk hematite doped with the tetravalent ions Sn4+ and Ti4+, for which T_M dramatically decreases, these dopants substantially increase T_M in thin films, far exceeding the bulk values. The normalized Fe LII-edge dichroism for T<T_M does not strongly depend on doping or temperature, except for an apparent increase of the peak amplitudes for T<100 K. We observed magnetic field-induced inversions of the dichroism peaks. By applying a magnetic field of 6.5 T on the Ti-doped sample, a transition into the T>T_M state was achieved. The temperature dependence of the critical field for the Sn-doped sample was characterized in detail. It was demonstrated the sample-to-sample variations of the Fe LIII-edge spectra were, for the most part, determined solely by the spin orientation state. Calculations of the polarization-depedent spectra based on a spin-multiplet model were in reasonable agreement with the experiment and showed a mixed excitation character of the peak structures.Comment: 8 pages, 8 figure

Searching for Massive Outflows in Holmberg IX X-1 and NGC 1313 X-1: The Iron K Band

We have analysed all the good quality XMM-Newton data publicly available for the bright ULXs Holmberg IX X-1 and NGC 1313 X-1, with the aim of searching for discrete emission or absorption features in the Fe K band that could provide observational evidence for the massive outflows predicted if these sources are accreting at substantially super-Eddington rates. We do not find statistically compelling evidence for any atomic lines, and the limits that are obtained have interesting consequences. Any features in the immediate Fe K energy band (6-7 keV) must have equivalent widths weaker than ~30 eV for Holmberg IX X-1, and weaker than ~50 eV for NGC 1313 X-1 (at 99 per cent confidence). In comparison to the sub-Eddington outflows observed in GRS 1915+105, which imprint iron absorption features with equivalent widths of ~30 eV, the limits obtained here appear quite stringent, particularly when Holmberg IX X-1 and NGC 1313 X-1 must be expelling at least 5-10 times as much material if they host black holes of similar masses. The difficulty in reconciling these observational limits with the presence of strong line-of-sight outflows suggests that either these sources are not launching such outflows, or that they must be directed away from our viewing angle.Comment: 11 pages, 5 figures, accepted for publication in MNRA

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

Do Neuro-Muscular Adaptations Occur in Endurance-Trained Boys and Men?

Most research on the effects of endurance training has focused on endurance training's health-related benefits and metabolic effects in both children and adults. The purpose of this study was to examine the neuromuscular effects of endurance training and to investigate whether they differ in children (9.0-12.9 years) and adults (18.4-35.6 years). Maximal isometric torque, rate of torque development (RTD), rate of muscle activation (Q30), electromechanical delay (EMD), and time to peak torque and peak RTD were determined by isokinetic dynamometry and surface electromyography (EMG) in elbow and knee flexion and extension. The subjects were 12 endurance-trained and 16 untrained boys, and 15 endurance-trained and 20 untrained men. The adults displayed consistently higher peak torque, RTD, and Q30, in both absolute and normalized values, whereas the boys had longer EMD (64.7+/-17.1 vs. 56.6+/-15.4 ms) and time to peak RTD (98.5+/-32.1 vs. 80.4+/-15.0 ms for boys and men, respectively). Q30, normalized for peak EMG amplitude, was the only observed training effect (1.95+/-1.16 vs. 1.10+/-0.67 ms for trained and untrained men, respectively). This effect could not be shown in the boys. The findings show normalized muscle strength and rate of activation to be lower in children compared with adults, regardless of training status. Because the observed higher Q30 values were not matched by corresponding higher performance measures in the trained men, the functional and discriminatory significance of Q30 remains unclear. Endurance training does not appear to affect muscle strength or rate of force development in either men or boys