3,160 research outputs found
Classifying pairs with trees for supervised biological network inference
Networks are ubiquitous in biology and computational approaches have been
largely investigated for their inference. In particular, supervised machine
learning methods can be used to complete a partially known network by
integrating various measurements. Two main supervised frameworks have been
proposed: the local approach, which trains a separate model for each network
node, and the global approach, which trains a single model over pairs of nodes.
Here, we systematically investigate, theoretically and empirically, the
exploitation of tree-based ensemble methods in the context of these two
approaches for biological network inference. We first formalize the problem of
network inference as classification of pairs, unifying in the process
homogeneous and bipartite graphs and discussing two main sampling schemes. We
then present the global and the local approaches, extending the later for the
prediction of interactions between two unseen network nodes, and discuss their
specializations to tree-based ensemble methods, highlighting their
interpretability and drawing links with clustering techniques. Extensive
computational experiments are carried out with these methods on various
biological networks that clearly highlight that these methods are competitive
with existing methods.Comment: 22 page
Algebraic shortcuts for leave-one-out cross-validation in supervised network inference
Supervised machine learning techniques have traditionally been very successful at reconstructing biological networks, such as protein-ligand interaction, protein-protein interaction and gene regulatory networks. Many supervised techniques for network prediction use linear models on a possibly nonlinear pairwise feature representation of edges. Recently, much emphasis has been placed on the correct evaluation of such supervised models. It is vital to distinguish between using a model to either predict new interactions in a given network or to predict interactions for a new vertex not present in the original network. This distinction matters because (i) the performance might dramatically differ between the prediction settings and (ii) tuning the model hyperparameters to obtain the best possible model depends on the setting of interest. Specific cross-validation schemes need to be used to assess the performance in such different prediction settings. In this work we discuss a state-of-the-art kernel-based network inference technique called two-step kernel ridge regression. We show that this regression model can be trained efficiently, with a time complexity scaling with the number of vertices rather than the number of edges. Furthermore, this framework leads to a series of cross-validation shortcuts that allow one to rapidly estimate the model performance for any relevant network prediction setting. This allows computational biologists to fully assess the capabilities of their models
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
Multi-omics integration accurately predicts cellular state in unexplored conditions for Escherichia coli.
A significant obstacle in training predictive cell models is the lack of integrated data sources. We develop semi-supervised normalization pipelines and perform experimental characterization (growth, transcriptional, proteome) to create Ecomics, a consistent, quality-controlled multi-omics compendium for Escherichia coli with cohesive meta-data information. We then use this resource to train a multi-scale model that integrates four omics layers to predict genome-wide concentrations and growth dynamics. The genetic and environmental ontology reconstructed from the omics data is substantially different and complementary to the genetic and chemical ontologies. The integration of different layers confers an incremental increase in the prediction performance, as does the information about the known gene regulatory and protein-protein interactions. The predictive performance of the model ranges from 0.54 to 0.87 for the various omics layers, which far exceeds various baselines. This work provides an integrative framework of omics-driven predictive modelling that is broadly applicable to guide biological discovery
Prediction of drugâtarget interaction networks from the integration of chemical and genomic spaces
Motivation: The identification of interactions between drugs and target proteins is a key area in genomic drug discovery. Therefore, there is a strong incentive to develop new methods capable of detecting these potential drugâtarget interactions efficiently
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