2,153 research outputs found
A hierarchical Bayesian model for predicting ecological interactions using scaled evolutionary relationships
Identifying undocumented or potential future interactions among species is a
challenge facing modern ecologists. Recent link prediction methods rely on
trait data, however large species interaction databases are typically sparse
and covariates are limited to only a fraction of species. On the other hand,
evolutionary relationships, encoded as phylogenetic trees, can act as proxies
for underlying traits and historical patterns of parasite sharing among hosts.
We show that using a network-based conditional model, phylogenetic information
provides strong predictive power in a recently published global database of
host-parasite interactions. By scaling the phylogeny using an evolutionary
model, our method allows for biological interpretation often missing from
latent variable models. To further improve on the phylogeny-only model, we
combine a hierarchical Bayesian latent score framework for bipartite graphs
that accounts for the number of interactions per species with the host
dependence informed by phylogeny. Combining the two information sources yields
significant improvement in predictive accuracy over each of the submodels
alone. As many interaction networks are constructed from presence-only data, we
extend the model by integrating a correction mechanism for missing
interactions, which proves valuable in reducing uncertainty in unobserved
interactions.Comment: To appear in the Annals of Applied Statistic
Multiscale virtual particle based elastic network model (MVP-ENM) for biomolecular normal mode analysis
In this paper, a multiscale virtual particle based elastic network model
(MVP-ENM) is proposed for biomolecular normal mode analysis. The multiscale
virtual particle model is proposed for the discretization of biomolecular
density data in different scales. Essentially, the model works as the
coarse-graining of the biomolecular structure, so that a delicate balance
between biomolecular geometric representation and computational cost can be
achieved. To form "connections" between these multiscale virtual particles, a
new harmonic potential function, which considers the influence from both mass
distributions and distance relations, is adopted between any two virtual
particles. Unlike the previous ENMs that use a constant spring constant, a
particle-dependent spring parameter is used in MVP-ENM. Two independent models,
i.e., multiscale virtual particle based Gaussian network model (MVP-GNM) and
multiscale virtual particle based anisotropic network model (MVP-ANM), are
proposed. Even with a rather coarse grid and a low resolution, the MVP-GNM is
able to predict the Debye-Waller factors (B-factors) with considerable good
accuracy. Similar properties have also been observed in MVP-ANM. More
importantly, in B-factor predictions, the mismatch between the predicted
results and experimental ones is predominantly from higher fluctuation regions.
Further, it is found that MVP-ANM can deliver a very consistent low-frequency
eigenmodes in various scales. This demonstrates the great potential of MVP-ANM
in the deformation analysis of low resolution data. With the multiscale
rigidity function, the MVP-ENM can be applied to biomolecular data represented
in density distribution and atomic coordinates. Further, the great advantage of
my MVP-ENM model in computational cost has been demonstrated by using two
poliovirus virus structures. Finally, the paper ends with a conclusion.Comment: 15 figures; 25 page
Innovative Hybridisation of Genetic Algorithms and Neural Networks in Detecting Marker Genes for Leukaemia Cancer
Methods for extracting marker genes that trigger the growth
of cancerous cells from a high level of complexity microarrays are of much interest from the computing community. Through the identified genes, the pathology of cancerous cells can be revealed and early precaution
can be taken to prevent further proliferation of cancerous cells. In this paper, we propose an innovative hybridised gene identification framework based on genetic algorithms and neural networks to identify marker genes for leukaemia disease. Our approach confirms that high classification
accuracy does not ensure the optimal set of genes have been identified and our model delivers a more promising set of genes even with a lower classification accurac
Proteome scanning to predict PDZ domain interactions using support vector machines
<p>Abstract</p> <p>Background</p> <p>PDZ domains mediate protein-protein interactions involved in important biological processes through the recognition of short linear motifs in their target proteins. Two recent independent studies have used protein microarray or phage display technology to detect PDZ domain interactions with peptide ligands on a large scale. Several computational predictors of PDZ domain interactions have been developed, however they are trained using only protein microarray data and focus on limited subsets of PDZ domains. An accurate predictor of genomic PDZ domain interactions would allow the proteomes of organisms to be scanned for potential binders. Such an application would require an accurate and precise predictor to avoid generating too many false positive hits given the large amount of possible interactors in a given proteome. Once validated these predictions will help to increase the coverage of current PDZ domain interaction networks and further our understanding of the roles that PDZ domains play in a variety of biological processes.</p> <p>Results</p> <p>We developed a PDZ domain interaction predictor using a support vector machine (SVM) trained with both protein microarray and phage display data. In order to use the phage display data for training, which only contains positive interactions, we developed a method to generate artificial negative interactions. Using cross-validation and a series of independent tests, we showed that our SVM successfully predicts interactions in different organisms. We then used the SVM to scan the proteomes of human, worm and fly to predict binders for several PDZ domains. Predictions were validated using known genomic interactions and published protein microarray experiments. Based on our results, new protein interactions potentially associated with Usher and Bardet-Biedl syndromes were predicted. A comparison of performance measures (F1 measure and FPR) for the SVM and published predictors demonstrated our SVM's improved accuracy and precision at proteome scanning.</p> <p>Conclusions</p> <p>We built an SVM using mouse and human experimental training data to predict PDZ domain interactions. We showed that it correctly predicts known interactions from proteomes of different organisms and is more accurate and precise at proteome scanning compared with published state-of-the-art predictors.</p
VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines
BACKGROUND: Vaccine development in the post-genomic era often begins with the in silico screening of genome information, with the most probable protective antigens being predicted rather than requiring causative microorganisms to be grown. Despite the obvious advantages of this approach – such as speed and cost efficiency – its success remains dependent on the accuracy of antigen prediction. Most approaches use sequence alignment to identify antigens. This is problematic for several reasons. Some proteins lack obvious sequence similarity, although they may share similar structures and biological properties. The antigenicity of a sequence may be encoded in a subtle and recondite manner not amendable to direct identification by sequence alignment. The discovery of truly novel antigens will be frustrated by their lack of similarity to antigens of known provenance. To overcome the limitations of alignment-dependent methods, we propose a new alignment-free approach for antigen prediction, which is based on auto cross covariance (ACC) transformation of protein sequences into uniform vectors of principal amino acid properties. RESULTS: Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. Every set consisted of 100 known antigens and 100 non-antigens. The derived models were tested by internal leave-one-out cross-validation and external validation using test sets. An additional five training sets for each class of antigens were used to test the stability of the discrimination between antigens and non-antigens. The models performed well in both validations showing prediction accuracy of 70% to 89%. The models were implemented in a server, which we call VaxiJen. CONCLUSION: VaxiJen is the first server for alignment-independent prediction of protective antigens. It was developed to allow antigen classification solely based on the physicochemical properties of proteins without recourse to sequence alignment. The server can be used on its own or in combination with alignment-based prediction methods. It is freely-available online at the URL:
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