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      Multitask Protein Function Prediction Through Task Dissimilarity

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          Abstract

          Automated protein function prediction is a challenging problem with distinctive features, such as the hierarchical organization of protein functions and the scarcity of annotated proteins for most biological functions. We propose a multitask learning algorithm addressing both issues. Unlike standard multitask algorithms, which use task (protein functions) similarity information as a bias to speed up learning, we show that dissimilarity information enforces separation of rare class labels from frequent class labels, and for this reason is better suited for solving unbalanced protein function prediction problems. We support our claim by showing that a multitask extension of the label propagation algorithm empirically works best when the task relatedness information is represented using a dissimilarity matrix as opposed to a similarity matrix. Moreover, the experimental comparison carried out on three model organism shows that our method has a more stable performance in both "protein-centric" and "function-centric" evaluation settings.

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          Most cited references33

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          Laplacian Eigenmaps for Dimensionality Reduction and Data Representation

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            Network-based prediction of protein function

            Functional annotation of proteins is a fundamental problem in the post-genomic era. The recent availability of protein interaction networks for many model species has spurred on the development of computational methods for interpreting such data in order to elucidate protein function. In this review, we describe the current computational approaches for the task, including direct methods, which propagate functional information through the network, and module-assisted methods, which infer functional modules within the network and use those for the annotation task. Although a broad variety of interesting approaches has been developed, further progress in the field will depend on systematic evaluation of the methods and their dissemination in the biological community.
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              An expanded evaluation of protein function prediction methods shows an improvement in accuracy

              Background A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1037-6) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                2016-11-03
                Article
                1611.00962
                ee7c878d-4974-4e5f-b7e7-ab61ff849736

                http://arxiv.org/licenses/nonexclusive-distrib/1.0/

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                Custom metadata
                68Q01
                12 pages, 5 figures
                stat.ML cs.LG q-bio.QM

                Quantitative & Systems biology,Machine learning,Artificial intelligence
                Quantitative & Systems biology, Machine learning, Artificial intelligence

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