Cargando…
LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes
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 therap...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9893534/ https://www.ncbi.nlm.nih.gov/pubmed/36732776 http://dx.doi.org/10.1186/s13040-023-00321-5 |
_version_ | 1784881547129651200 |
---|---|
author | Alasiri, Abdulrahman Karczewski, Konrad J. Cole, Brian Loza, Bao-Li Moore, Jason H. van der Laan, Sander W. Asselbergs, Folkert W. Keating, Brendan J. van Setten, Jessica |
author_facet | Alasiri, Abdulrahman Karczewski, Konrad J. Cole, Brian Loza, Bao-Li Moore, Jason H. van der Laan, Sander W. Asselbergs, Folkert W. Keating, Brendan J. van Setten, Jessica |
author_sort | Alasiri, Abdulrahman |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13040-023-00321-5. |
format | Online Article Text |
id | pubmed-9893534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-98935342023-02-03 LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes Alasiri, Abdulrahman Karczewski, Konrad J. Cole, Brian Loza, Bao-Li Moore, Jason H. van der Laan, Sander W. Asselbergs, Folkert W. Keating, Brendan J. van Setten, Jessica BioData Min Software 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13040-023-00321-5. BioMed Central 2023-02-02 /pmc/articles/PMC9893534/ /pubmed/36732776 http://dx.doi.org/10.1186/s13040-023-00321-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Software Alasiri, Abdulrahman Karczewski, Konrad J. Cole, Brian Loza, Bao-Li Moore, Jason H. van der Laan, Sander W. Asselbergs, Folkert W. Keating, Brendan J. van Setten, Jessica LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes |
title | LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes |
title_full | LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes |
title_fullStr | LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes |
title_full_unstemmed | LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes |
title_short | LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes |
title_sort | loftk: a framework for fully automated calculation of predicted loss-of-function variants and genes |
topic | Software |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9893534/ https://www.ncbi.nlm.nih.gov/pubmed/36732776 http://dx.doi.org/10.1186/s13040-023-00321-5 |
work_keys_str_mv | AT alasiriabdulrahman loftkaframeworkforfullyautomatedcalculationofpredictedlossoffunctionvariantsandgenes AT karczewskikonradj loftkaframeworkforfullyautomatedcalculationofpredictedlossoffunctionvariantsandgenes AT colebrian loftkaframeworkforfullyautomatedcalculationofpredictedlossoffunctionvariantsandgenes AT lozabaoli loftkaframeworkforfullyautomatedcalculationofpredictedlossoffunctionvariantsandgenes AT moorejasonh loftkaframeworkforfullyautomatedcalculationofpredictedlossoffunctionvariantsandgenes AT vanderlaansanderw loftkaframeworkforfullyautomatedcalculationofpredictedlossoffunctionvariantsandgenes AT asselbergsfolkertw loftkaframeworkforfullyautomatedcalculationofpredictedlossoffunctionvariantsandgenes AT keatingbrendanj loftkaframeworkforfullyautomatedcalculationofpredictedlossoffunctionvariantsandgenes AT vansettenjessica loftkaframeworkforfullyautomatedcalculationofpredictedlossoffunctionvariantsandgenes |