Tissue-spEcific mrNa iSoform functIOnal Networks (TENSION) Predictions
Alternative Splicing produces multiple mRNA isoforms of a gene which have important diverse roles such as regulation of gene expression, human heritable diseases, and response to environmental stresses. However, very little has been done to assign functions at the mRNA isoform level. Functional networks, where the interactions are quantified by their probability of being involved in the same biological process are typically generated at the gene level. We use a diverse array of tissue-specific RNA-seq datasets and sequence information to train random forest models for predicting the functional networks following a leave-one-tissue-out strategy. Since there is no mRNA isoform-level gold standard, we use single isoform genes co-annotated to Gene Ontology biological process annotations, Kyoto Encyclopedia of Genes and Genomes pathways, BioCyc pathways and protein-protein interactions as functionally related (positive pair). To generate the non-functional pairs (negative pair), we use the Gene Ontology annotations tagged with “NOT” qualifier. We describe 17 Tissue-spEcific mrNa iSoform functIOnal Networks (TENSION) in addition to an organism level reference functional network for mouse. We validate our predictions by comparing its performance with previous methods, randomized positive and negative class labels, updated Gene Ontology annotations, and by literature evidence.
This material is based upon work supported by the National Science Foundation under Grant IOS-1062546. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number ACI-1548562. This work used the XSEDE Comet cluster at San Diego Supercomputer Center (SDSC) through allocation TG-BIO170049.
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- Animal cell and molecular biology
- Animal structure and function
- Bioinformatics and computational biology not elsewhere classified
- Gene expression (incl. microarray and other genome-wide approaches)
- Genetics not elsewhere classified
- Genome structure and regulation
- Plant cell and molecular biology
- Proteomics and intermolecular interactions (excl. medical proteomics)
- Biomolecular modelling and design
- Proteins and peptides
- Knowledge representation and reasoning