ArticlePLoS computational biology2013
Systematically differentiating functions for alternatively spliced isoforms through integrating RNA-seq data.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- 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
- Landscape of alternative splicing and polyadenylation during growth and development of muscles in pigs.Communications biology · 2024Article
- Concordant Gene Expression and Alternative Splicing Regulation under Abiotic Stresses in Arabidopsis.Genes · 2024Article
- IsoFrog: a reversible jump Markov Chain Monte Carlo feature selection-based method for predicting isoform functions.Bioinformatics (Oxford, England) · 2023Article
- Discovering NDM-1 inhibitors using molecular substructure embeddings representations.Journal of integrative bioinformatics · 2023Article
- An expectation-maximization framework for comprehensive prediction of isoform-specific functions.Bioinformatics (Oxford, England) · 2023Article
- Bridging the splicing gap in human genetics with long-read RNA sequencing: finding the protein isoform drivers of disease.Human molecular genetics · 2022Review
- Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing.Cell reports · 2021Article
- Alternative splicing and gene expression play contrasting roles in the parallel phenotypic evolution of a salmonid fish.Molecular ecology · 2021Article
- 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
- IsoResolve: predicting splice isoform functions by integrating gene and isoform-level features with domain adaptation.Bioinformatics (Oxford, England) · 2021Article
- Structural basis of the selective activation of enzyme isoforms: Allosteric response to activators of β1- and β2-containing AMPK complexes.Computational and structural biotechnology journal · 2021Article
- Pooled analysis of radiation hybrids identifies loci for growth and drug action in mammalian cells.Genome research · 2020Article
- Alternative splicing of leptin receptor overlapping transcript in osteosarcoma.Experimental biology and medicine (Maywood, N.J.) · 2020Article
- Computational Methods for Predicting Functions at the mRNA Isoform Level.International journal of molecular sciences · 2020Review
- ClusterMine: A knowledge-integrated clustering approach based on expression profiles of gene sets.Journal of bioinformatics and computational biology · 2020Article
- ISOGO: Functional annotation of protein-coding splice variants.Scientific reports · 2020Article
- A Functional Kinase Is Necessary for Cyclin-Dependent Kinase G1 (CDKG1) to Maintain Fertility at High Ambient Temperature inFrontiers in plant science · 2020Article
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Authors and funding
7 authors.
Funding
Abstract
Integrating large-scale functional genomic data has significantly accelerated our understanding of gene functions. However, no algorithm has been developed to differentiate functions for isoforms of the same gene using high-throughput genomic data. This is because standard supervised learning requires 'ground-truth' functional annotations, which are lacking at the isoform level. To address this challenge, we developed a generic framework that interrogates public RNA-seq data at the transcript level to differentiate functions for alternatively spliced isoforms. For a specific function, our algorithm identifies the 'responsible' isoform(s) of a gene and generates classifying models at the isoform level instead of at the gene level. Through cross-validation, we demonstrated that our algorithm is effective in assigning functions to genes, especially the ones with multiple isoforms, and robust to gene expression levels and removal of homologous gene pairs. We identified genes in the mouse whose isoforms are predicted to have disparate functionalities and experimentally validated the 'responsible' isoforms using data from mammary tissue. With protein structure modeling and experimental evidence, we further validated the predicted isoform functional differences for the genes Cdkn2a and Anxa6. Our generic framework is the first to predict and differentiate functions for alternatively spliced isoforms, instead of genes, using genomic data. It is extendable to any base machine learner and other species with alternatively spliced isoforms, and shifts the current gene-centered function prediction to isoform-level predictions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.