Annotating newly sequenced genomes and determining alternative isoforms from long-read RNA data are complex and incompletely solved problems. Here we present IsoQuant—a computational tool using intron graphs that accurately reconstructs transcripts both with and without reference genome annotation. For novel transcript discovery, IsoQuant reduces the false-positive rate fivefold and 2.5-fold for Oxford Nanopore reference-based or reference-free mode, respectively. IsoQuant also improves performance for Pacific Biosciences data.
Long reads are reshaping RNA biology. However, determining alternative isoforms from long-read RNA data is a complex and incompletely solved problem even when the reference genome is known. Here we present IsoQuant - a reference-based tool that accurately discovers novel transcripts with at least 3-fold lower false positive rate and 1.8-fold increase in F1-score compared to other tools for Oxford Nanopore data. IsoQuant also increases performance for Pacific Biosciences data.
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