ArticleNature communications2016
The complete local genotype-phenotype landscape for the alternative splicing of a human exon.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 121 citations in OpenAlex.
- Comprehensive review and assessment of multi-species splicing variant prediction: task-specific deep learning models and genomic foundation models.Briefings in bioinformatics · 2026Review
- The functional landscape of coding variation in the familial hypercholesterolemia geneScience (New York, N.Y.) · 2026Article
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- High-Throughput Methods for Variant Functional Assessment in Cardiac Disease.Circulation. Genomic and precision medicine · 2026Review
- Control of gene output by intron RNA structure.bioRxiv : the preprint server for biology · 2025Article
- Massively parallel assay of human splice variants reveals cis-regulatory drivers of disease-associated and cell type-specific splicing regulation.bioRxiv : the preprint server for biology · 2025Article
- Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4.Nature structural & molecular biology · 2025Article
- Article
- Deep indel mutagenesis reveals the regulatory and modulatory architecture of alternative exon splicing.Nature communications · 2025Article
- From computational models of the splicing code to regulatory mechanisms and therapeutic implications.Nature reviews. Genetics · 2025Review
- Gauge fixing for sequence-function relationships.PLoS computational biology · 2025Article
- MMRT: MultiMut Recursive Tree for predicting functional effects of high-order protein variants from low-order variants.Computational and structural biotechnology journal · 2025Article
- Decoding biology with massively parallel reporter assays and machine learning.Genes & development · 2024Review
- Gauge fixing for sequence-function relationships.bioRxiv : the preprint server for biology · 2024Article
- Benchmarking splice variant prediction algorithms using massively parallel splicing assays.Genome biology · 2023Article
- Deciphering RNA splicing logic with interpretable machine learning.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Splicing defects in rare diseases: transcriptomics and machine learning strategies towards genetic diagnosis.Briefings in bioinformatics · 2023Review
- Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks.Science advances · 2023Article
- Large-scale functional screen identifies genetic variants with splicing effects in modern and archaic humans.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Benchmarking splice variant prediction algorithms using massively parallel splicing assays.bioRxiv : the preprint server for biology · 2023Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The properties of genotype-phenotype landscapes are crucial for understanding evolution but are not characterized for most traits. Here, we present a >95% complete local landscape for a defined molecular function-the alternative splicing of a human exon (FAS/CD95 exon 6, involved in the control of apoptosis). The landscape provides important mechanistic insights, revealing that regulatory information is dispersed throughout nearly every nucleotide in an exon, that the exon is more robust to the effects of mutations than its immediate neighbours in genotype space, and that high mutation sensitivity (evolvability) will drive the rapid divergence of alternative splicing between species unless it is constrained by selection. Moreover, the extensive epistasis in the landscape predicts that exonic regulatory sequences may diverge between species even when exon inclusion levels are functionally important and conserved by selection.
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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.