ArticleHuman mutation2019
Future directions for high-throughput splicing assays in precision medicine.
Article in Human mutation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Capturing artificial intelligence applications' value proposition in healthcare - a qualitative research study.BMC health services research · 2024Pooled it
- Assessing the Functional Significance of Novel and Rare Variants of theInternational journal of molecular sciences · 2025Article
- Hidden Splicing Variants in Inherited Retinal Degeneration: Discovery and Functional Insight.Investigative ophthalmology & visual science · 2025Article
- Sequence-Independent RNA Sensing in Living Mammalian Cells.bioRxiv : the preprint server for biology · 2025Article
- Alternative splicing in stem cells and development: research progress and emerging technologies.Cell regeneration (London, England) · 2025Review
- Data-driven insights to inform splice-altering variant assessment.American journal of human genetics · 2025Article
- SpliceVarDB: A comprehensive database of experimentally validated human splicing variants.American journal of human genetics · 2024Article
- CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods.Genome biology · 2024Article
- Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects.Nature reviews. Genetics · 2023Review
- Minigene-based splicing analysis and ACMG/AMP-based tentative classification of 56 ATM variants.The Journal of pathology · 2022Article
- Massively parallel reporter assays discover de novo exonic splicing mutants in paralogs of Autism genes.PLoS genetics · 2022Article
- Functional assessment of somatic STK11 variants identified in primary human non-small cell lung cancers.Carcinogenesis · 2021Article
- Article
- Allele-specific alternative splicing and its functional genetic variants in human tissues.Genome research · 2021Article
- Reports from the fifth edition of CAGI: The Critical Assessment of Genome Interpretation.Human mutation · 2019Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Classification of variants of unknown significance is a challenging technical problem in clinical genetics. As up to one-third of disease-causing mutations are thought to affect pre-mRNA splicing, it is important to accurately classify splicing mutations in patient sequencing data. Several consortia and healthcare systems have conducted large-scale patient sequencing studies, which discover novel variants faster than they can be classified. Here, we compare the advantages and limitations of several high-throughput splicing assays aimed at mitigating this bottleneck, and describe a data set of ~5,000 variants that we analyzed using our Massively Parallel Splicing Assay (MaPSy). The Critical Assessment of Genome Interpretation group (CAGI) organized a challenge, in which participants submitted machine learning models to predict the splicing effects of variants in this data set. We discuss the winning submission of the challenge (MMSplice) which outperformed existing software. Finally, we highlight methods to overcome the limitations of MaPSy and similar assays, such as tissue-specific splicing, the effect of surrounding sequence context, classifying intronic variants, synthesizing large exons, and amplifying complex libraries of minigene species. Further development of these assays will greatly benefit the field of clinical genetics, which lack high-throughput methods for variant interpretation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.