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Abstract MotivationAlternative splicing generates multiple isoforms from a single gene, greatly increasing the functional diversity of a genome. Although gene functions have been well studied, little is known about the specific functions of isoforms, making accurate prediction of isoform functions highly desirable. However, the existing approaches to predicting isoform functions are far from satisfactory due to at least two reasons: (i) unlike genes, isoform-level functional annotations are scarce. (ii) The information of isoform functions is concealed in various types of data including isoform sequences, co-expression relationship among isoforms, etc. ResultsIn this study, we present a novel approach, DIFFUSE (Deep learning-based prediction of IsoForm FUnctions from Sequences and Expression), to predict isoform functions. To integrate various types of data, our approach adopts a hybrid framework by first using a deep neural network (DNN) to predict the functions of isoforms from their genomic sequences and then refining the prediction using a conditional random field (CRF) based on co-expression relationship. To overcome the lack of isoform-level ground truth labels, we further propose an iterative semi-supervised learning algorithm to train both the DNN and CRF together. Our extensive computational experiments demonstrate that DIFFUSE could effectively predict the functions of isoforms and genes. It achieves an average area under the receiver operating characteristics curve of 0.840 and area under the precision–recall curve of 0.581 over 4184 GO functional categories, which are significantly higher than the state-of-the-art methods. We further validate the prediction results by analyzing the correlation between functional similarity, sequence similarity, expression similarity and structural similarity, as well as the consistency between the predicted functions and some well-studied functional features of isoform sequences. Availability and implementationhttps://github.com/haochenucr/DIFFUSE. Supplementary informationSupplementary data are available at Bioinformatics online.
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Structure Meets Sequences: Predicting Network of Co-evolving Sequences
Co-evolving sequences are ubiquitous in a variety of applications, where different sequences are often inherently inter-connected with each other. We refer to such sequences, together with their inherent connections modeled as a structured network, as network of co-evolving sequences (NoCES). Typical NoCES applications in- clude road traffic monitoring, company revenue prediction, motion capture, etc. To date, it remains a daunting challenge to accurately model NoCES due to the coupling between network structure and sequences. In this paper, we propose to modeling NoCES with the aim of simultaneously capturing both the dynamics and the inter- play between network structure and sequences. Specifically, we propose a joint learning framework to alternatively update the network representations and sequence representations as the se- quences evolve over time. A unique feature of our framework lies in that it can deal with the case when there are co-evolving sequences on both network nodes and edges. Experimental evaluations on four real datasets demonstrate that the proposed approach (1) out- performs the existing competitors in terms of prediction accuracy, and (2) scales linearly w.r.t. the sequence length and the network size.
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- PAR ID:
- 10332503
- Date Published:
- Journal Name:
- WSDM
- Page Range / eLocation ID:
- 1090 to 1098
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1145/3488560.3498411
