Small variant benchmark from a complete assembly of X and Y chromosomes
Abstract The sex chromosomes contain complex, important genes impacting medical phenotypes, but differ from the autosomes in their ploidy and large repetitive regions. To enable technology developers along with research and clinical laboratories to evaluate variant detection on male sex chromosomes...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55710-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544418294759424 |
|---|---|
| author | Justin Wagner Nathan D. Olson Jennifer McDaniel Lindsay Harris Brendan J. Pinto David Jáspez Adrián Muñoz-Barrera Luis A. Rubio-Rodríguez José M. Lorenzo-Salazar Carlos Flores Sayed Mohammad Ebrahim Sahraeian Giuseppe Narzisi Marta Byrska-Bishop Uday S. Evani Chunlin Xiao Juniper A. Lake Peter Fontana Craig Greenberg Donald Freed Mohammed Faizal Eeman Mootor Paul C. Boutros Lisa Murray Kishwar Shafin Andrew Carroll Fritz J. Sedlazeck Melissa Wilson Justin M. Zook |
| author_facet | Justin Wagner Nathan D. Olson Jennifer McDaniel Lindsay Harris Brendan J. Pinto David Jáspez Adrián Muñoz-Barrera Luis A. Rubio-Rodríguez José M. Lorenzo-Salazar Carlos Flores Sayed Mohammad Ebrahim Sahraeian Giuseppe Narzisi Marta Byrska-Bishop Uday S. Evani Chunlin Xiao Juniper A. Lake Peter Fontana Craig Greenberg Donald Freed Mohammed Faizal Eeman Mootor Paul C. Boutros Lisa Murray Kishwar Shafin Andrew Carroll Fritz J. Sedlazeck Melissa Wilson Justin M. Zook |
| author_sort | Justin Wagner |
| collection | DOAJ |
| description | Abstract The sex chromosomes contain complex, important genes impacting medical phenotypes, but differ from the autosomes in their ploidy and large repetitive regions. To enable technology developers along with research and clinical laboratories to evaluate variant detection on male sex chromosomes X and Y, we create a small variant benchmark set with 111,725 variants for the Genome in a Bottle HG002 reference material. We develop an active evaluation approach to demonstrate the benchmark set reliably identifies errors in challenging genomic regions and across short and long read callsets. We show how complete assemblies can expand benchmarks to difficult regions, but highlight remaining challenges benchmarking variants in long homopolymers and tandem repeats, complex gene conversions, copy number variable gene arrays, and human satellites. |
| format | Article |
| id | doaj-art-2d384cdcf1274ec7b44aa9c241ff7ea0 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-2d384cdcf1274ec7b44aa9c241ff7ea02025-01-12T12:30:55ZengNature PortfolioNature Communications2041-17232025-01-011611710.1038/s41467-024-55710-zSmall variant benchmark from a complete assembly of X and Y chromosomesJustin Wagner0Nathan D. Olson1Jennifer McDaniel2Lindsay Harris3Brendan J. Pinto4David Jáspez5Adrián Muñoz-Barrera6Luis A. Rubio-Rodríguez7José M. Lorenzo-Salazar8Carlos Flores9Sayed Mohammad Ebrahim Sahraeian10Giuseppe Narzisi11Marta Byrska-Bishop12Uday S. Evani13Chunlin Xiao14Juniper A. Lake15Peter Fontana16Craig Greenberg17Donald Freed18Mohammed Faizal Eeman Mootor19Paul C. Boutros20Lisa Murray21Kishwar Shafin22Andrew Carroll23Fritz J. Sedlazeck24Melissa Wilson25Justin M. Zook26Material Measurement Laboratory, National Institute of Standards and Technology, 100 Bureau Dr.Material Measurement Laboratory, National Institute of Standards and Technology, 100 Bureau Dr.Material Measurement Laboratory, National Institute of Standards and Technology, 100 Bureau Dr.Material Measurement Laboratory, National Institute of Standards and Technology, 100 Bureau Dr.Center for Evolution & Medicine and School of Life Sciences, Arizona State University, Tempe, AZ 85281 USA - Department of Zoology, Milwaukee Public MuseumGenomics Division, Instituto Tecnológico y de Energías Renovables (ITER)Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER)Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER)Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER)Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER)Roche Sequencing SolutionsNew York Genome CenterNew York Genome CenterNew York Genome CenterNational Center for Biotechnology Information, National Library of Medicine, National Institutes of HealthPacific BiosciencesInformation Technology Laboratory, National Institute of Standards and Technology, 100 Bureau Dr. Mailstop 8940Information Technology Laboratory, National Institute of Standards and Technology, 100 Bureau Dr. Mailstop 8940Sentieon Inc.Department of Human Genetics, University of California Los AngelesDepartment of Human Genetics, University of California Los AngelesIlluminaGoogle Inc, 1600 Amphitheatre PkwyGoogle Inc, 1600 Amphitheatre PkwyBaylor College of Medicine Human Genome Sequencing CenterCenter for Evolution & Medicine and School of Life Sciences, Arizona State UniversityMaterial Measurement Laboratory, National Institute of Standards and Technology, 100 Bureau Dr.Abstract The sex chromosomes contain complex, important genes impacting medical phenotypes, but differ from the autosomes in their ploidy and large repetitive regions. To enable technology developers along with research and clinical laboratories to evaluate variant detection on male sex chromosomes X and Y, we create a small variant benchmark set with 111,725 variants for the Genome in a Bottle HG002 reference material. We develop an active evaluation approach to demonstrate the benchmark set reliably identifies errors in challenging genomic regions and across short and long read callsets. We show how complete assemblies can expand benchmarks to difficult regions, but highlight remaining challenges benchmarking variants in long homopolymers and tandem repeats, complex gene conversions, copy number variable gene arrays, and human satellites.https://doi.org/10.1038/s41467-024-55710-z |
| spellingShingle | Justin Wagner Nathan D. Olson Jennifer McDaniel Lindsay Harris Brendan J. Pinto David Jáspez Adrián Muñoz-Barrera Luis A. Rubio-Rodríguez José M. Lorenzo-Salazar Carlos Flores Sayed Mohammad Ebrahim Sahraeian Giuseppe Narzisi Marta Byrska-Bishop Uday S. Evani Chunlin Xiao Juniper A. Lake Peter Fontana Craig Greenberg Donald Freed Mohammed Faizal Eeman Mootor Paul C. Boutros Lisa Murray Kishwar Shafin Andrew Carroll Fritz J. Sedlazeck Melissa Wilson Justin M. Zook Small variant benchmark from a complete assembly of X and Y chromosomes Nature Communications |
| title | Small variant benchmark from a complete assembly of X and Y chromosomes |
| title_full | Small variant benchmark from a complete assembly of X and Y chromosomes |
| title_fullStr | Small variant benchmark from a complete assembly of X and Y chromosomes |
| title_full_unstemmed | Small variant benchmark from a complete assembly of X and Y chromosomes |
| title_short | Small variant benchmark from a complete assembly of X and Y chromosomes |
| title_sort | small variant benchmark from a complete assembly of x and y chromosomes |
| url | https://doi.org/10.1038/s41467-024-55710-z |
| work_keys_str_mv | AT justinwagner smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT nathandolson smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT jennifermcdaniel smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT lindsayharris smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT brendanjpinto smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT davidjaspez smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT adrianmunozbarrera smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT luisarubiorodriguez smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT josemlorenzosalazar smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT carlosflores smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT sayedmohammadebrahimsahraeian smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT giuseppenarzisi smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT martabyrskabishop smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT udaysevani smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT chunlinxiao smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT juniperalake smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT peterfontana smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT craiggreenberg smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT donaldfreed smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT mohammedfaizaleemanmootor smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT paulcboutros smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT lisamurray smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT kishwarshafin smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT andrewcarroll smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT fritzjsedlazeck smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT melissawilson smallvariantbenchmarkfromacompleteassemblyofxandychromosomes AT justinmzook smallvariantbenchmarkfromacompleteassemblyofxandychromosomes |