125 research outputs found
Gene Function Classification Using Bayesian Models with Hierarchy-Based Priors
We investigate the application of hierarchical classification schemes to the
annotation of gene function based on several characteristics of protein
sequences including phylogenic descriptors, sequence based attributes, and
predicted secondary structure. We discuss three Bayesian models and compare
their performance in terms of predictive accuracy. These models are the
ordinary multinomial logit (MNL) model, a hierarchical model based on a set of
nested MNL models, and a MNL model with a prior that introduces correlations
between the parameters for classes that are nearby in the hierarchy. We also
provide a new scheme for combining different sources of information. We use
these models to predict the functional class of Open Reading Frames (ORFs) from
the E. coli genome. The results from all three models show substantial
improvement over previous methods, which were based on the C5 algorithm. The
MNL model using a prior based on the hierarchy outperforms both the
non-hierarchical MNL model and the nested MNL model. In contrast to previous
attempts at combining these sources of information, our approach results in a
higher accuracy rate when compared to models that use each data source alone.
Together, these results show that gene function can be predicted with higher
accuracy than previously achieved, using Bayesian models that incorporate
suitable prior information
A stochastic individual-based model to explore the role of spatial interactions and antigen recognition in the immune response against solid tumours
FRM is funded by the Engineering and Physical Sciences Research Council (EPSRC).Spatial interactions between cancer and immune cells, as well as the recognition of tumour antigens by cells of the immune system, play a key role in the immune response against solid tumours. The existing mathematical models generally focus only on one of these key aspects. We present here a spatial stochastic individual-based model that explicitly captures antigen expression and recognition. In our model, each cancer cell is characterised by an antigen profile which can change over time due to either epimutations or mutations. The immune response against the cancer cells is initiated by the dendritic cells that recognise the tumour antigens and present them to the cytotoxic T cells. Consequently, T cells become activated against the tumour cells expressing such antigens. Moreover, the differences in movement between inactive and active immune cells are explicitly taken into account by the model. Computational simulations of our model clarify the conditions for the emergence of tumour clearance, dormancy or escape, and allow us to assess the impact of antigenic heterogeneity of cancer cells on the efficacy of immune action. Ultimately, our results highlight the complex interplay between spatial interactions and adaptive mechanisms that underpins the immune response against solid tumours, and suggest how this may be exploited to further develop cancer immunotherapies.PostprintPeer reviewe
Vitamin blood concentration and vitamin supplementation in bottlenose dolphins (Tursiops truncatus) in European facilities
The restorative role of annexin A1 at the blood–brain barrier
Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune
system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the
study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the
peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule
in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective
actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the
possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS
vasculature, and its potential for repairing blood–brain barrier damage in disease and aging
Dialética da autonomia dos equilíbrios nos conflitos entre pacientes e cirurgiões oncológicos
Accuracy of cartilage-specific 3-Tesla 3D-DESS magnetic resonance imaging in the diagnosis of chondral lesions: comparison with knee arthroscopy
IKKβ-mediated inflammatory myeloid cell activation exacerbates experimental autoimmune encephalomyelitis by potentiating Th1/Th17 cell activation and compromising blood brain barrier
- …