Related Experiment Video
Updated: Jan 27, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
ORE identifies extreme expression effects enriched for rare variants
F Richter1, G E Hoffman2,3, K B Manheimer4
1Graduate School of Biomedical Sciences.
Motivation:
Non-coding rare variants (RVs) may contribute to Mendelian disorders but have been challenging to study due to small sample sizes, genetic heterogeneity and uncertainty about relevant non-coding features. Previous studies identified RVs associated with expression outliers, but varying outlier definitions were employed and no comprehensive open-source software was developed.
Results:
We developed Outlier-RV Enrichment (ORE) to identify biologically-meaningful non-coding RVs. We implemented ORE combining whole-genome sequencing and cardiac RNAseq from congenital heart defect patients from the Pediatric Cardiac Genomics Consortium and deceased adults from Genotype-Tissue Expression. Use of rank-based outliers maximized sensitivity while a most extreme outlier approach maximized specificity. Rarer variants had stronger associations, suggesting they are under negative selective pressure and providing a basis for investigating their contribution to Mendelian disorders.
Availability And Implementation:
ORE, source code, and documentation are available at https://pypi.python.org/pypi/ore under the MIT license.
Supplementary Information:
Supplementary data are available at Bioinformatics online.
Related Concept Videos
Histone Variants at the Centromere
Absolute and Local Extreme Values
Buffer Effectiveness
The buffer capacity is the amount of acid or base that can be added to a given volume...
Framing Effects
What is Gene Expression?
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Identifying Statistically Significant Differences: The F-Test

