Alasiri, A;
Karczewski, KJ;
Cole, B;
Loza, BL;
Moore, JH;
van der Laan, SW;
Asselbergs, FW;
... van Setten, J; + view all
(2023)
LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.
BioData Mining
, 16
(1)
, Article 3. 10.1186/s13040-023-00321-5.
Preview |
Text
s13040-023-00321-5.pdf - Published Version Download (1MB) | Preview |
Abstract
Background: Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants. Results: We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent. Conclusions: LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK.
| Type: | Article |
|---|---|
| Title: | LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13040-023-00321-5 |
| Publisher version: | https://doi.org/10.1186/s13040-023-00321-5 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Loss-of-Function variants, Knockout genes, Compound heterozygotes, Human genetic |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10165468 |
Archive Staff Only
 |
View Item |
