6,338 research outputs found
Integration of relational and hierarchical network information for protein function prediction
<p>Abstract</p> <p>Background</p> <p>In the current climate of high-throughput computational biology, the inference of a protein's function from related measurements, such as protein-protein interaction relations, has become a canonical task. Most existing technologies pursue this task as a classification problem, on a term-by-term basis, for each term in a database, such as the Gene Ontology (GO) database, a popular rigorous vocabulary for biological functions. However, ontology structures are essentially hierarchies, with certain top to bottom annotation rules which protein function predictions should in principle follow. Currently, the most common approach to imposing these hierarchical constraints on network-based classifiers is through the use of transitive closure to predictions.</p> <p>Results</p> <p>We propose a probabilistic framework to integrate information in relational data, in the form of a protein-protein interaction network, and a hierarchically structured database of terms, in the form of the GO database, for the purpose of protein function prediction. At the heart of our framework is a factorization of local neighborhood information in the protein-protein interaction network across successive ancestral terms in the GO hierarchy. We introduce a classifier within this framework, with computationally efficient implementation, that produces GO-term predictions that naturally obey a hierarchical 'true-path' consistency from root to leaves, without the need for further post-processing.</p> <p>Conclusion</p> <p>A cross-validation study, using data from the yeast <it>Saccharomyces cerevisiae</it>, shows our method offers substantial improvements over both standard 'guilt-by-association' (i.e., Nearest-Neighbor) and more refined Markov random field methods, whether in their original form or when post-processed to artificially impose 'true-path' consistency. Further analysis of the results indicates that these improvements are associated with increased predictive capabilities (i.e., increased positive predictive value), and that this increase is consistent uniformly with GO-term depth. Additional <it>in silico </it>validation on a collection of new annotations recently added to GO confirms the advantages suggested by the cross-validation study. Taken as a whole, our results show that a hierarchical approach to network-based protein function prediction, that exploits the ontological structure of protein annotation databases in a principled manner, can offer substantial advantages over the successive application of 'flat' network-based methods.</p
PTOMSM: A modified version of Topological Overlap Measure used for predicting Protein-Protein Interaction Network
A variety of methods are developed to integrating diverse biological data to predict novel interaction relationship between proteins. However, traditional integration can only generate protein interaction pairs within existing relationships. Therefore, we propose a modified version of Topological Overlap Measure to identify not only extant direct PPIs links, but also novel protein interactions that can be indirectly inferred from various relationships between proteins. Our method is more powerful than a naïve Bayesian-network-based integration in PPI prediction, and could generate more reliable candidate PPIs. Furthermore, we examined the influence of the sizes of training and test datasets on prediction, and further demonstrated the effectiveness of PTOMSM in predicting PPI. More importantly, this method can be extended naturally to predict other types of biological networks, and may be combined with Bayesian method to further improve the prediction
Ranking relations using analogies in biological and information networks
Analogical reasoning depends fundamentally on the ability to learn and
generalize about relations between objects. We develop an approach to
relational learning which, given a set of pairs of objects
,
measures how well other pairs A:B fit in with the set . Our work
addresses the following question: is the relation between objects A and B
analogous to those relations found in ? Such questions are
particularly relevant in information retrieval, where an investigator might
want to search for analogous pairs of objects that match the query set of
interest. There are many ways in which objects can be related, making the task
of measuring analogies very challenging. Our approach combines a similarity
measure on function spaces with Bayesian analysis to produce a ranking. It
requires data containing features of the objects of interest and a link matrix
specifying which relationships exist; no further attributes of such
relationships are necessary. We illustrate the potential of our method on text
analysis and information networks. An application on discovering functional
interactions between pairs of proteins is discussed in detail, where we show
that our approach can work in practice even if a small set of protein pairs is
provided.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS321 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Identification of functionally related enzymes by learning-to-rank methods
Enzyme sequences and structures are routinely used in the biological sciences
as queries to search for functionally related enzymes in online databases. To
this end, one usually departs from some notion of similarity, comparing two
enzymes by looking for correspondences in their sequences, structures or
surfaces. For a given query, the search operation results in a ranking of the
enzymes in the database, from very similar to dissimilar enzymes, while
information about the biological function of annotated database enzymes is
ignored.
In this work we show that rankings of that kind can be substantially improved
by applying kernel-based learning algorithms. This approach enables the
detection of statistical dependencies between similarities of the active cleft
and the biological function of annotated enzymes. This is in contrast to
search-based approaches, which do not take annotated training data into
account. Similarity measures based on the active cleft are known to outperform
sequence-based or structure-based measures under certain conditions. We
consider the Enzyme Commission (EC) classification hierarchy for obtaining
annotated enzymes during the training phase. The results of a set of sizeable
experiments indicate a consistent and significant improvement for a set of
similarity measures that exploit information about small cavities in the
surface of enzymes
Hybrid Approach of Relation Network and Localized Graph Convolutional Filtering for Breast Cancer Subtype Classification
Network biology has been successfully used to help reveal complex mechanisms
of disease, especially cancer. On the other hand, network biology requires
in-depth knowledge to construct disease-specific networks, but our current
knowledge is very limited even with the recent advances in human cancer
biology. Deep learning has shown a great potential to address the difficult
situation like this. However, deep learning technologies conventionally use
grid-like structured data, thus application of deep learning technologies to
the classification of human disease subtypes is yet to be explored. Recently,
graph based deep learning techniques have emerged, which becomes an opportunity
to leverage analyses in network biology. In this paper, we proposed a hybrid
model, which integrates two key components 1) graph convolution neural network
(graph CNN) and 2) relation network (RN). We utilize graph CNN as a component
to learn expression patterns of cooperative gene community, and RN as a
component to learn associations between learned patterns. The proposed model is
applied to the PAM50 breast cancer subtype classification task, the standard
breast cancer subtype classification of clinical utility. In experiments of
both subtype classification and patient survival analysis, our proposed method
achieved significantly better performances than existing methods. We believe
that this work is an important starting point to realize the upcoming
personalized medicine.Comment: 8 pages, To be published in proceeding of IJCAI 201
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