4,037 research outputs found

    Investigating the biological relevance in trained embedding representations of protein sequences

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    As genome sequencing is becoming faster and cheaper, an abundance of DNA and protein sequence data is available. However, experimental annotation of structural or functional information develops at a much slower pace. Therefore, machine learning techniques have been widely adopted to make accurate predictions on unseen sequence data. In recent years, deep learning has been gaining popularity, as it allows for effective end-to-end learning. One consideration for its application on sequence data is the choice for a suitable and effective sequence representation strategy. In this paper, we investigate the significance of three common encoding schemes on the multi-label prediction problem of Gene Ontology (GO) term annotation, namely a one-hot encoding, an ad-hoc trainable embedding, and pre-trained protein vectors, using different hyper-parameters. We found that traditional unigram one-hot encodings achieved very good results, only slightly outperformed by unigram ad-hoc trainable embeddings and bigram pre-trained embeddings (by at most 3%for the F maxscore), suggesting the exploration of different encoding strategies to be potentially beneficial. Most interestingly, when analyzing and visualizing the trained embeddings, we found that biologically relevant (dis)similarities between amino acid n-grams were implicitly learned, which were consistent with their physiochemical properties

    A multi-species functional embedding integrating sequence and network structure

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    A key challenge to transferring knowledge between species is that different species have fundamentally different genetic architectures. Initial computational approaches to transfer knowledge across species have relied on measures of heredity such as genetic homology, but these approaches suffer from limitations. First, only a small subset of genes have homologs, limiting the amount of knowledge that can be transferred, and second, genes change or repurpose functions, complicating the transfer of knowledge. Many approaches address this problem by expanding the notion of homology by leveraging high-throughput genomic and proteomic measurements, such as through network alignment. In this work, we take a new approach to transferring knowledge across species by expanding the notion of homology through explicit measures of functional similarity between proteins in different species. Specifically, our kernel-based method, HANDL (Homology Assessment across Networks using Diffusion and Landmarks), integrates sequence and network structure to create a functional embedding in which proteins from different species are embedded in the same vector space. We show that inner products in this space and the vectors themselves capture functional similarity across species, and are useful for a variety of functional tasks. We perform the first whole-genome method for predicting phenologs, generating many that were previously identified, but also predicting new phenologs supported from the biological literature. We also demonstrate the HANDL embedding captures pairwise gene function, in that gene pairs with synthetic lethal interactions are significantly separated in HANDL space, and the direction of separation is conserved across species. Software for the HANDL algorithm is available at http://bit.ly/lrgr-handl.Published versio
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