BackgroundA 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.ResultsWe 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.ConclusionsThe 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 materialThe online version of this article (doi:10.1186/s13059-016-1037-6) contains supplementary material, which is available to authorized users.
Gene function prediction is used to assign biological or biochemical functions to genes, which continues to be a challenging problem in modern biology. Genes may exhibit many functions simultaneously, and these functions are organized into a hierarchy, such as a directed acyclic graph (DAG) for Gene Ontology (GO). Because of these characteristics, gene function prediction can be seen as a typical hierarchical multi-label classification (HMC) task. A novel HMC method based on neural networks is proposed in this article for predicting gene function based on GO. The proposed method belongs to a local approach by transferring the HMC task to a set of subtasks. There are three strategies implemented in this method to improve its performance. First, to tackle the imbalanced data set problem when building the training data set for each class, negative instances selecting policy and SMOTE approach are used to preprocess each imbalanced training data set. Second, a particular multi-layer perceptron (MLP) is designed for each node in GO. Third, a post processing method based on the Bayesian network is used to guarantee that the results are consistent with the hierarchy constraint. The experimental results indicate that the proposed HMC-MLPN method is a promising method for gene function prediction based on a comparison with two other state-of-the-art methods.
Gene function prediction is a complicated and challenging hierarchical multi-label classification (HMC) task, in which genes may have many functions at the same time and these functions are organized in a hierarchy. This paper proposed a novel HMC algorithm for solving this problem based on the Gene Ontology (GO), the hierarchy of which is a directed acyclic graph (DAG) and is more difficult to tackle. In the proposed algorithm, the HMC task is firstly changed into a set of binary classification tasks. Then, two measures are implemented in the algorithm to enhance the HMC performance by considering the hierarchy structure during the learning procedures. Firstly, negative instances selecting policy associated with the SMOTE approach are proposed to alleviate the imbalanced data set problem. Secondly, a nodes interaction method is introduced to combine the results of binary classifiers. It can guarantee that the predictions are consistent with the hierarchy constraint. The experiments on eight benchmark yeast data sets annotated by the Gene Ontology show the promising performance of the proposed algorithm compared with other state-of-the-art algorithms.
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