262 research outputs found
The identification of informative genes from multiple datasets with increasing complexity
Background
In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes.
Results
In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes.
Conclusions
We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events
JWST MIRI and NIRCam Unveil Previously Unseen Infrared Stellar Populations in NGC 6822
NGC 6822 is a nearby (\sim490 kpc) non-interacting low-metallicity (0.2
Z_\odot) dwarf galaxy which hosts several prominent Hii regions, including
sites of highly embedded active star formation. In this work, we present an
imaging survey of NGC 6822 conducted with the NIRCam and MIRI instruments
onboard JWST. We provide a description of the data reduction, source
extraction, and stellar population identifications from combined near- and
mid-infrared (IR) photometry. Our NIRCam observations reach seven magnitudes
deeper than previous JHKs surveys of this galaxy, which were sensitive to just
below the tip of the red giant branch (TRGB). These JWST observations thus
reveal for the first time in the near-IR the red clump stellar population and
extend nearly three magnitudes deeper. In the mid-IR, we observe roughly two
magnitudes below the TRGB with the MIRI F770W and F1000W filters. With these
improvements in sensitivity, we produce a catalogue of \sim900,000 point
sources over an area of \sim 6.0 x 4.3 arcmin2. We present several NIRCam and
MIRI colour-magnitude diagrams and discuss which colour combinations provide
useful separations of various stellar populations to aid in future JWST
observation planning. Finally, we find populations of carbon- and oxygen-rich
asymptotic giant branch stars which will assist in improving our understanding
of dust production in low-metallicity, early Universe analogue galaxies
Comparative Transcriptional and Translational Analysis of Leptospiral Outer Membrane Protein Expression in Response to Temperature
Leptospirosis, caused by Leptospira spp., is a disease of worldwide significance affecting millions of people annually. Bacteria of this species are spread by various carrier animals, including rodents and domestic livestock, which shed the leptospires via their urine into the environment. Humans become infected through direct contact with carrier animals or indirectly via contaminated water or soil. Temperature is a key trigger used by many bacteria to sense changes in environmental conditions, including entry from the environment into the host. This study was the first comprehensive research into changes occurring in the outer membrane of Leptospira in response to temperature and how these changes correlate with gene expression changes. An understanding of the regulation and function of these proteins is important as they may provide an adaptation and survival advantage for the microorganism which may enhance its ability to infect hosts and cause disease. Our data suggest regulation of proteins in the outer membrane which may possibly be a mechanism to minimise interactions with the host immune response
Measurement of the Total Active 8B Solar Neutrino Flux at the Sudbury Neutrino Observatory with Enhanced Neutral Current Sensitivity
The Sudbury Neutrino Observatory (SNO) has precisely determined the total
active (nu_x) 8B solar neutrino flux without assumptions about the energy
dependence of the nu_e survival probability. The measurements were made with
dissolved NaCl in the heavy water to enhance the sensitivity and signature for
neutral-current interactions. The flux is found to be 5.21 +/- 0.27 (stat) +/-
0.38 (syst) x10^6 cm^{-2}s^{-1}, in agreement with previous measurements and
standard solar models. A global analysis of these and other solar and reactor
neutrino results yields Delta m^{2} = 7.1^{+1.2}_{-0.6}x10^{-5} ev^2 and theta
= 32.5^{+2.4}_{-2.3} degrees. Maximal mixing is rejected at the equivalent of
5.4 standard deviations.Comment: Submitted to Phys. Rev. Let
Electron Antineutrino Search at the Sudbury Neutrino Observatory
Upper limits on the \nuebar flux at the Sudbury Neutrino Observatory have
been set based on the \nuebar charged-current reaction on deuterium. The
reaction produces a positron and two neutrons in coincidence. This distinctive
signature allows a search with very low background for \nuebar's from the Sun
and other potential sources. Both differential and integral limits on the
\nuebar flux have been placed in the energy range from 4 -- 14.8 MeV. For an
energy-independent \nu_e --> \nuebar conversion mechanism, the integral limit
on the flux of solar \nuebar's in the energy range from 4 -- 14.8 MeV is found
to be \Phi_\nuebar <= 3.4 x 10^4 cm^{-2} s^{-1} (90% C.L.), which corresponds
to 0.81% of the standard solar model 8B \nu_e flux of 5.05 x 10^6 cm^{-2}
s^{-1}, and is consistent with the more sensitive limit from KamLAND in the 8.3
-- 14.8 MeV range of 3.7 x 10^2 cm^{-2} s^{-1} (90% C.L.). In the energy range
from 4 -- 8 MeV, a search for \nuebar's is conducted using coincidences in
which only the two neutrons are detected. Assuming a \nuebar spectrum for the
neutron induced fission of naturally occurring elements, a flux limit of
Phi_\nuebar <= 2.0 x 10^6 cm^{-2} s^{-1}(90% C.L.) is obtained.Comment: submitted to Phys. Rev.
Global Proteome Analysis of Leptospira interrogans
Comparative global proteome analyses were performed on Leptospira interrogans serovar Copenhageni grown under conventional in vitro conditions and those mimicking in vivo conditions (iron limitation and serum presence). Proteomic analyses were conducted using iTRAQ and LC-ESI-tandem mass spectrometry complemented with two-dimensional gel electrophoresis and MALDI-TOF mass spec-trometry. A total of 563 proteins were identified in this study. Altered expression of 65 proteins, including upregulation of the L. interrogans virulence factor Loa22 and 5 novel proteins with homology to virulence factors found in other pathogens, was observed between the comparative conditions. Immunoblot analyses confirmed upregulation of 5 of the known or putative virulence factors in L. interrogans exposed to the in vivo-like environmental conditions. Further, ELISA analyses using serum from patients with leptospirosis and immunofluorescence studies performed on liver sections derived from L. interrogans-infected hamsters verified expression of all but one of the identified proteins during infection. These studies, which represent the first documented comparative global proteome analysis of Leptospira, demonstrated proteome alterations under conditions that mimic in vivo infection and allowed for the identification of novel putative L. interrogans virulence factors
Measurement of the rate of nu_e + d --> p + p + e^- interactions produced by 8B solar neutrinos at the Sudbury Neutrino Observatory
Solar neutrinos from the decay of B have been detected at the Sudbury
Neutrino Observatory (SNO) via the charged current (CC) reaction on deuterium
and by the elastic scattering (ES) of electrons. The CC reaction is sensitive
exclusively to nu_e's, while the ES reaction also has a small sensitivity to
nu_mu's and nu_tau's. The flux of nu_e's from ^8B decay measured by the CC
reaction rate is
\phi^CC(nu_e) = 1.75 +/- 0.07 (stat)+0.12/-0.11 (sys.) +/- 0.05(theor) x 10^6
/cm^2 s.
Assuming no flavor transformation, the flux inferred from the ES reaction
rate is
\phi^ES(nu_x) = 2.39+/-0.34 (stat.)+0.16}/-0.14 (sys) x 10^6 /cm^2 s.
Comparison of \phi^CC(nu_e) to the Super-Kamiokande Collaboration's precision
value of \phi^ES(\nu_x) yields a 3.3 sigma difference, providing evidence that
there is a non-electron flavor active neutrino component in the solar flux. The
total flux of active ^8B neutrinos is thus determined to be 5.44 +/-0.99 x
10^6/cm^2 s, in close agreement with the predictions of solar models.Comment: 6 pages (LaTex), 3 figures, submitted to Phys. Rev. Letter
Revival of the magnetar PSR J1622-4950: observations with MeerKAT, Parkes, XMM-Newton, Swift, Chandra, and NuSTAR
New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and
NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a
quiescent state since at least early 2015, reactivated between 2017 March 19
and April 5. The radio flux density, while variable, is approximately 100x
larger than during its dormant state. The X-ray flux one month after
reactivation was at least 800x larger than during quiescence, and has been
decaying exponentially on a 111+/-19 day timescale. This high-flux state,
together with a radio-derived rotational ephemeris, enabled for the first time
the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV
pulsed fraction is comparable to the smallest observed for magnetars. The
overall pulsar geometry inferred from polarized radio emission appears to be
broadly consistent with that determined 6-8 years earlier. However, rotating
vector model fits suggest that we are now seeing radio emission from a
different location in the magnetosphere than previously. This indicates a novel
way in which radio emission from magnetars can differ from that of ordinary
pulsars. The torque on the neutron star is varying rapidly and unsteadily, as
is common for magnetars following outburst, having changed by a factor of 7
within six months of reactivation.Comment: Published in ApJ (2018 April 5); 13 pages, 4 figure
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