ArticleNucleic acids research2014
High-resolution functional annotation of human transcriptome: predicting isoform functions by a novel multiple instance-based label propagation method.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Proteoform medicine: characterizing and targeting protein forms in human disease.Nature reviews. Genetics · 2026Review
- DeepISO: deep learning-powered prediction of protein-protein interaction rewiring generated by alternative splicing.Genome biology · 2026Article
- The functional landscape of alternative splicing in hematopoietic lineage commitment.Nature communications · 2026Article
- CrossIsoFun: predicting isoform functions using the integration of multi-omics data.Bioinformatics (Oxford, England) · 2024Article
- IsoFrog: a reversible jump Markov Chain Monte Carlo feature selection-based method for predicting isoform functions.Bioinformatics (Oxford, England) · 2023Article
- An expectation-maximization framework for comprehensive prediction of isoform-specific functions.Bioinformatics (Oxford, England) · 2023Article
- Evolution of isoform-level gene expression patterns across tissues during lotus species divergence.The Plant journal : for cell and molecular biology · 2022Article
- Bridging the splicing gap in human genetics with long-read RNA sequencing: finding the protein isoform drivers of disease.Human molecular genetics · 2022Review
- A Global Analysis of Alternative Splicing ofCurrent genomics · 2022Article
- FINER: enhancing the prediction of tissue-specific functions of isoforms by refining isoform interaction networks.NAR genomics and bioinformatics · 2021Article
- Assessing the functional relevance of splice isoforms.NAR genomics and bioinformatics · 2021Article
- A network-based computational framework to predict and differentiate functions for gene isoforms using exon-level expression data.Methods (San Diego, Calif.) · 2021Article
- IsoResolve: predicting splice isoform functions by integrating gene and isoform-level features with domain adaptation.Bioinformatics (Oxford, England) · 2021Article
- A general index for linear and nonlinear correlations for high dimensional genomic data.BMC genomics · 2020Article
- Computational Methods for Predicting Functions at the mRNA Isoform Level.International journal of molecular sciences · 2020Review
- ISOGO: Functional annotation of protein-coding splice variants.Scientific reports · 2020Article
- Tissue-specific mouse mRNA isoform networks.Scientific reports · 2019Article
- Exploring the functional impact of alternative splicing on human protein isoforms using available annotation sources.Briefings in bioinformatics · 2019Review
- DeepIsoFun: a deep domain adaptation approach to predict isoform functions.Bioinformatics (Oxford, England) · 2019Article
- DIFFUSE: predicting isoform functions from sequences and expression profiles via deep learning.Bioinformatics (Oxford, England) · 2019Article
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7 authors.
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Abstract
Alternative transcript processing is an important mechanism for generating functional diversity in genes. However, little is known about the precise functions of individual isoforms. In fact, proteins (translated from transcript isoforms), not genes, are the function carriers. By integrating multiple human RNA-seq data sets, we carried out the first systematic prediction of isoform functions, enabling high-resolution functional annotation of human transcriptome. Unlike gene function prediction, isoform function prediction faces a unique challenge: the lack of the training data--all known functional annotations are at the gene level. To address this challenge, we modelled the gene-isoform relationships as multiple instance data and developed a novel label propagation method to predict functions. Our method achieved an average area under the receiver operating characteristic curve of 0.67 and assigned functions to 15 572 isoforms. Interestingly, we observed that different functions have different sensitivities to alternative isoform processing, and that the function diversity of isoforms from the same gene is positively correlated with their tissue expression diversity. Finally, we surveyed the literature to validate our predictions for a number of apoptotic genes. Strikingly, for the famous 'TP53' gene, we not only accurately identified the apoptosis regulation function of its five isoforms, but also correctly predicted the precise direction of the regulation.
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