Cargando…

The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates

In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutati...

Descripción completa

Detalles Bibliográficos
Autores principales: Bergeron, Lucie A, Besenbacher, Søren, Turner, Tychele, Versoza, Cyril J, Wang, Richard J, Price, Alivia Lee, Armstrong, Ellie, Riera, Meritxell, Carlson, Jedidiah, Chen, Hwei-yen, Hahn, Matthew W, Harris, Kelley, Kleppe, April Snøfrid, López-Nandam, Elora H, Moorjani, Priya, Pfeifer, Susanne P, Tiley, George P, Yoder, Anne D, Zhang, Guojie, Schierup, Mikkel H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830884/
https://www.ncbi.nlm.nih.gov/pubmed/35018888
http://dx.doi.org/10.7554/eLife.73577
_version_ 1784648378008731648
author Bergeron, Lucie A
Besenbacher, Søren
Turner, Tychele
Versoza, Cyril J
Wang, Richard J
Price, Alivia Lee
Armstrong, Ellie
Riera, Meritxell
Carlson, Jedidiah
Chen, Hwei-yen
Hahn, Matthew W
Harris, Kelley
Kleppe, April Snøfrid
López-Nandam, Elora H
Moorjani, Priya
Pfeifer, Susanne P
Tiley, George P
Yoder, Anne D
Zhang, Guojie
Schierup, Mikkel H
author_facet Bergeron, Lucie A
Besenbacher, Søren
Turner, Tychele
Versoza, Cyril J
Wang, Richard J
Price, Alivia Lee
Armstrong, Ellie
Riera, Meritxell
Carlson, Jedidiah
Chen, Hwei-yen
Hahn, Matthew W
Harris, Kelley
Kleppe, April Snøfrid
López-Nandam, Elora H
Moorjani, Priya
Pfeifer, Susanne P
Tiley, George P
Yoder, Anne D
Zhang, Guojie
Schierup, Mikkel H
author_sort Bergeron, Lucie A
collection PubMed
description In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and appropriately accounting for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a ‘Mutationathon,’ a competition organized among five research labs to compare germline mutation rate estimates for a single pedigree of rhesus macaques. We report almost a twofold variation in the final estimated rate among groups using different post-alignment processing, calling, and filtering criteria, and provide details into the sources of variation across studies. Though the difference among estimates is not statistically significant, this discrepancy emphasizes the need for standardized methods in mutation rate estimations and the difficulty in comparing rates from different studies. Finally, this work aims to provide guidelines for computational and statistical benchmarks for future studies interested in identifying germline mutations from pedigrees.
format Online
Article
Text
id pubmed-8830884
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-88308842022-02-14 The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates Bergeron, Lucie A Besenbacher, Søren Turner, Tychele Versoza, Cyril J Wang, Richard J Price, Alivia Lee Armstrong, Ellie Riera, Meritxell Carlson, Jedidiah Chen, Hwei-yen Hahn, Matthew W Harris, Kelley Kleppe, April Snøfrid López-Nandam, Elora H Moorjani, Priya Pfeifer, Susanne P Tiley, George P Yoder, Anne D Zhang, Guojie Schierup, Mikkel H eLife Evolutionary Biology In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and appropriately accounting for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a ‘Mutationathon,’ a competition organized among five research labs to compare germline mutation rate estimates for a single pedigree of rhesus macaques. We report almost a twofold variation in the final estimated rate among groups using different post-alignment processing, calling, and filtering criteria, and provide details into the sources of variation across studies. Though the difference among estimates is not statistically significant, this discrepancy emphasizes the need for standardized methods in mutation rate estimations and the difficulty in comparing rates from different studies. Finally, this work aims to provide guidelines for computational and statistical benchmarks for future studies interested in identifying germline mutations from pedigrees. eLife Sciences Publications, Ltd 2022-01-12 /pmc/articles/PMC8830884/ /pubmed/35018888 http://dx.doi.org/10.7554/eLife.73577 Text en © 2022, Bergeron et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Evolutionary Biology
Bergeron, Lucie A
Besenbacher, Søren
Turner, Tychele
Versoza, Cyril J
Wang, Richard J
Price, Alivia Lee
Armstrong, Ellie
Riera, Meritxell
Carlson, Jedidiah
Chen, Hwei-yen
Hahn, Matthew W
Harris, Kelley
Kleppe, April Snøfrid
López-Nandam, Elora H
Moorjani, Priya
Pfeifer, Susanne P
Tiley, George P
Yoder, Anne D
Zhang, Guojie
Schierup, Mikkel H
The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates
title The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates
title_full The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates
title_fullStr The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates
title_full_unstemmed The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates
title_short The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates
title_sort mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates
topic Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830884/
https://www.ncbi.nlm.nih.gov/pubmed/35018888
http://dx.doi.org/10.7554/eLife.73577
work_keys_str_mv AT bergeronluciea themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT besenbachersøren themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT turnertychele themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT versozacyrilj themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT wangrichardj themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT pricealivialee themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT armstrongellie themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT rierameritxell themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT carlsonjedidiah themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT chenhweiyen themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT hahnmattheww themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT harriskelley themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT kleppeaprilsnøfrid themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT lopeznandamelorah themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT moorjanipriya themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT pfeifersusannep themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT tileygeorgep themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT yoderanned themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT zhangguojie themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT schierupmikkelh themutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT bergeronluciea mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT besenbachersøren mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT turnertychele mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT versozacyrilj mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT wangrichardj mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT pricealivialee mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT armstrongellie mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT rierameritxell mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT carlsonjedidiah mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT chenhweiyen mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT hahnmattheww mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT harriskelley mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT kleppeaprilsnøfrid mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT lopeznandamelorah mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT moorjanipriya mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT pfeifersusannep mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT tileygeorgep mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT yoderanned mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT zhangguojie mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates
AT schierupmikkelh mutationathonhighlightstheimportanceofreachingstandardizationinestimatesofpedigreebasedgermlinemutationrates