ArticlePloS one2017
Orion: Detecting regions of the human non-coding genome that are intolerant to variation using population genetics.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 169 citations in OpenAlex.
- GhostKnockoff inference empowers identification of putative causal variants in genome-wide association studies.Nature communications · 2022Pooled it
- Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance.Genome medicine · 2021Pooled it
- Evolving computational paradigms for noncoding variant pathogenicity prediction.Frontiers in molecular biosciences · 2026Review
- The landscape of fitness effects of putatively functional noncoding mutations in humans.bioRxiv : the preprint server for biology · 2025Article
- Diverse ancestral representation improves genetic intolerance metrics.Nature communications · 2025Article
- PSAP-Genomic-Regions: A Method Leveraging Population Data to Prioritize Coding and Non-Coding Variants in Whole Genome Sequencing for Rare Disease Diagnosis.Genetic epidemiology · 2025Article
- In silico generation and augmentation of regulatory variants from massively parallel reporter assay using conditional variational autoencoder.bioRxiv : the preprint server for biology · 2024Article
- Topologically associating domains define the impact of de novo promoter variants on autism spectrum disorder risk.Cell genomics · 2024Article
- VarCards2: an integrated genetic and clinical database for ACMG-AMP variant-interpretation guidelines in the human whole genome.Nucleic acids research · 2024Article
- Article
- Article
- Performance Comparison of Computational Methods for the Prediction of the Function and Pathogenicity of Non-coding Variants.Genomics, proteomics & bioinformatics · 2023Article
- Exploration of Tools for the Interpretation of Human Non-Coding Variants.International journal of molecular sciences · 2022Review
- Testing for association with rare variants in the coding and non-coding genome: RAVA-FIRST, a new approach based on CADD deleteriousness score.PLoS genetics · 2022Article
- MiRLog and dbmiR: Prioritization and functional annotation tools to study human microRNA sequence variants.Human mutation · 2022Article
- Cancer-driving mutations are enriched in genic regions intolerant to germline variation.Science advances · 2022Article
- Article
- Review
- Prioritizing non-coding regions based on human genomic constraint and sequence context with deep learning.Nature communications · 2021Article
- Rare variant association testing in the non-coding genome.Human genetics · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
There is broad agreement that genetic mutations occurring outside of the protein-coding regions play a key role in human disease. Despite this consensus, we are not yet capable of discerning which portions of non-coding sequence are important in the context of human disease. Here, we present Orion, an approach that detects regions of the non-coding genome that are depleted of variation, suggesting that the regions are intolerant of mutations and subject to purifying selection in the human lineage. We show that Orion is highly correlated with known intolerant regions as well as regions that harbor putatively pathogenic variation. This approach provides a mechanism to identify pathogenic variation in the human non-coding genome and will have immediate utility in the diagnostic interpretation of patient genomes and in large case control studies using whole-genome sequences.
Indexed as
Identifiers
What OpenQuestion holds
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.