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Register a new userAnalysis of Novel Annotations in the Gene Ontology for Boosting the Selection of Negative Examples
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Added by
Marco Frasca
Publication date
2018
fields
Informatics Engineering
and research's language is
English
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Public repositories for genome and proteome annotations, such as the Gene Ontology (GO), rarely stores negative annotations, i.e. proteins not possessing a given function. This leaves undefined or ill defined the set of negative examples, which is crucial for training the majority of machine learning methods inferring proteins functions. Automated techniques to choose reliable negative proteins are thereby required to train accurate function prediction models. This study proposes the first extensive analysis of the temporal evolution of protein annotations in the GO repository. Novel annotations registered through the years have been analyzed to verify the presence of annotation patterns in the GO hierarchy. Our research supplied fundamental clues about proteins likely to be unreliable as negative examples, that we verified into a novel algorithm of our own construction, validated on two organisms in a genome wide fashion against approaches proposed to choose negative examples in the context of functional prediction.
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Stratifying cancer patients based on their gene expression levels allows improving diagnosis, survival analysis and treatment planning. However, such data is extremely highly dimensional as it contains expression values for over 20000 genes per patient, and the number of samples in the datasets is low. To deal with such settings, we propose to incorporate prior biological knowledge about genes from ontologies into the machine learning system for the task of patient classification given their gene expression data. We use ontology embeddings that capture the semantic similarities between the genes to direct a Graph Convolutional Network, and therefore sparsify the network connections. We show this approach provides an advantage for predicting clinical targets from high-dimensional low-sample data.
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