ArticleGenome biology2016
Human splicing diversity and the extent of unannotated splice junctions across human RNA-seq samples on the Sequence Read Archive.
Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70 citing papers in PubMed, 121 citations in OpenAlex.
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- Splicing QTL mapping in stimulated macrophages associates low-usage splice junctions with immune-mediated disease risk.Nature communications · 2025Article
- Large-scale RNA-Seq mining reveals ciclopirox olamine induces TDP-43 cryptic exons.Nature communications · 2025Article
- Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.Molecular cell · 2025Article
- Splicing accuracy varies across human introns, tissues, age and disease.Nature communications · 2025Article
- Contrasting and combining transcriptome complexity captured by short and long RNA sequencing reads.Genome research · 2024Article
- Progerin mRNA expression in non-HGPS patients is correlated with widespread shifts in transcript isoforms.NAR genomics and bioinformatics · 2024Article
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- Developmental isoform diversity in the human neocortex informs neuropsychiatric risk mechanisms.Science (New York, N.Y.) · 2024Article
- The unusual gene architecture of polyubiquitin is created by dual-specific splice sites.Genome biology · 2024Article
- SpliceProt 2.0: A Sequence Repository of Human, Mouse, and Rat Proteoforms.International journal of molecular sciences · 2024Article
- MAJIQlopedia: an encyclopedia of RNA splicing variations in human tissues and cancer.Nucleic acids research · 2024Article
- DiffSegR: an RNA-seq data driven method for differential expression analysis using changepoint detection.NAR genomics and bioinformatics · 2023Article
- SpliceVault predicts the precise nature of variant-associated mis-splicing.Nature genetics · 2023Article
- IntroVerse: a comprehensive database of introns across human tissues.Nucleic acids research · 2023Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundGene annotations, such as those in GENCODE, are derived primarily from alignments of spliced cDNA sequences and protein sequences. The impact of RNA-seq data on annotation has been confined to major projects like ENCODE and Illumina Body Map 2.0.
resultsWe aligned 21,504 Illumina-sequenced human RNA-seq samples from the Sequence Read Archive (SRA) to the human genome and compared detected exon-exon junctions with junctions in several recent gene annotations. We found 56,861 junctions (18.6%) in at least 1000 samples that were not annotated, and their expression associated with tissue type. Junctions well expressed in individual samples tended to be annotated. Newer samples contributed few novel well-supported junctions, with the vast majority of detected junctions present in samples before 2013. We compiled junction data into a resource called intropolis available at http://intropolis.rail.bio . We used this resource to search for a recently validated isoform of the ALK gene and characterized the potential functional implications of unannotated junctions with publicly available TRAP-seq data.
conclusionsConsidering only the variation contained in annotation may suffice if an investigator is interested only in well-expressed transcript isoforms. However, genes that are not generally well expressed and nonetheless present in a small but significant number of samples in the SRA are likelier to be incompletely annotated. The rate at which evidence for novel junctions has been added to the SRA has tapered dramatically, even to the point of an asymptote. Now is perhaps an appropriate time to update incomplete annotations to include splicing present in the now-stable snapshot provided by the SRA.
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