期刊
GENETICS IN MEDICINE
卷 22, 期 7, 页码 1181-1190出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/s41436-020-0780-y
关键词
clinical genetics; medical genetics; alternative splicing; diagnostic markers; RNA-seq
资金
- National Institute of General Medical Sciences of the National Institutes of Health [R01GM128096]
- NIH/Eunice Kennedy Shriver National Institute of Child Health (NICHD) fellowship [F30HD098803]
Purpose RNA-seq is a promising approach to improve diagnoses by detecting pathogenic aberrations in RNA splicing that are missed by DNA sequencing. RNA-seq is typically performed on clinically accessible tissues (CATs) from blood and skin. RNA tissue specificity makes it difficult to identify aberrations in relevant but nonaccessible tissues (non-CATs). We determined how RNA-seq from CATs represent splicing in and across genes and non-CATs. Methods We quantified RNA splicing in 801 RNA-seq samples from 56 different adult and fetal tissues from Genotype-Tissue Expression Project (GTEx) and ArrayExpress. We identified genes and splicing events in each non-CAT and determined when RNA-seq in each CAT would inadequately represent them. We developed an online resource, MAJIQ-CAT, for exploring our analysis for specific genes and tissues. Results In non-CATs, 40.2% of genes have splicing that is inadequately represented by at least one CAT; 6.3% of genes have splicing inadequately represented by all CATs. A majority (52.1%) of inadequately represented genes are lowly expressed in CATs (transcripts per million (TPM) < 1), but 5.8% are inadequately represented despite being well expressed (TPM > 10). Conclusion Many splicing events in non-CATs are inadequately evaluated using RNA-seq from CATs. MAJIQ-CAT allows users to explore which accessible tissues, if any, best represent splicing in genes and tissues of interest.
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