Abstract

Products of multiexon genes, especially in higher organisms, are a mixture of isoforms with different or even opposing functions, and therefore need to be treated separately. However, most studies and available resources such as Gene Ontology provide only gene-level function annotations, and therefore lose the differential information at the isoform level. Here we report MIsoMine, a high-resolution portal to multiple levels of functional information of alternatively spliced isoforms in the mouse. This data portal provides tissue-specific expression patterns and co-expression networks, along with such previously published functional genomic data as protein domains, predicted isoform-level functions and functional relationships. The core utility of MIsoMine is allowing users to explore a preprocessed, quality-controlled set of RNA-seq data encompassing diverse tissues and cell lineages. Tissue-specific co-expression networks were established, allowing a 2D ranking of isoforms and tissues by co-expression patterns. The results of the multiple isoforms of the same gene are presented in parallel to facilitate direct comparison, with cross-talking to prioritized functions at the isoform level. MIsoMine provides the first isoform-level resolution effort at genome-scale. We envision that this data portal will be a valuable resource for exploring functional genomic data, and will complement the existing functionalities of the mouse genome informatics database and the gene expression database for the laboratory mouse.Database URL: http://guanlab.ccmb.med.umich.edu/misomine/

Highlights

  • Alternative splicing is a fundamental process in multicellular organisms, through which a single gene produces multiple transcripts

  • Recent accumulation of RNA-seq data and state-of-the-art analytic tools, including but not limited to TopHat [9], Cufflinks [10] and Sailfish [11], have made the estimation of expression levels at the isoform-level possible. Such advancement has stimulated functional genomic data integration at the isoform level [2]. Such progress calls for the establishment of a data portal that provides tissue-specific expression and co-expression patterns analogous to what have been established at the gene level [12,13,14,15,16]

  • We previously developed a suite of algorithms for predicting isoform-level functions and functional relationships through integrating RNA-seq data and other publicly available functional genomic data [1, 2, 20, 21]

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Summary

Introduction

Alternative splicing is a fundamental process in multicellular organisms, through which a single gene produces multiple transcripts. The resulting protein isoforms may have large differences in their 3D-structures, expression patterns, tissue specificity and biological functions [1,2,3,4]. MIsoMine provides curated and quality-controlled meta-data from RNA-seq expression and tissue-specific co-expression networks through an interactive web interface.

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