IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30930-3.html
   My bibliography  Save this article

Robust and accurate estimation of paralog-specific copy number for duplicated genes using whole-genome sequencing

Author

Listed:
  • Timofey Prodanov

    (University of California)

  • Vikas Bansal

    (University of California)

Abstract

The human genome contains hundreds of low-copy repeats (LCRs) that are challenging to analyze using short-read sequencing technologies due to extensive copy number variation and ambiguity in read mapping. Copy number and sequence variants in more than 150 duplicated genes that overlap LCRs have been implicated in monogenic and complex human diseases. We describe a computational tool, Parascopy, for estimating the aggregate and paralog-specific copy number of duplicated genes using whole-genome sequencing (WGS). Parascopy is an efficient method that jointly analyzes reads mapped to different repeat copies without the need for global realignment. It leverages multiple samples to mitigate sequencing bias and to identify reliable paralogous sequence variants (PSVs) that differentiate repeat copies. Analysis of WGS data for 2504 individuals from diverse populations showed that Parascopy is robust to sequencing bias, has higher accuracy compared to existing methods and enables prioritization of pathogenic copy number changes in duplicated genes.

Suggested Citation

  • Timofey Prodanov & Vikas Bansal, 2022. "Robust and accurate estimation of paralog-specific copy number for duplicated genes using whole-genome sequencing," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30930-3
    DOI: 10.1038/s41467-022-30930-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30930-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30930-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Ryan E. Mills & Klaudia Walter & Chip Stewart & Robert E. Handsaker & Ken Chen & Can Alkan & Alexej Abyzov & Seungtai Chris Yoon & Kai Ye & R. Keira Cheetham & Asif Chinwalla & Donald F. Conrad & Yuta, 2011. "Mapping copy number variation by population-scale genome sequencing," Nature, Nature, vol. 470(7332), pages 59-65, February.
    2. Daniel Taliun & Daniel N. Harris & Michael D. Kessler & Jedidiah Carlson & Zachary A. Szpiech & Raul Torres & Sarah A. Gagliano Taliun & André Corvelo & Stephanie M. Gogarten & Hyun Min Kang & Achille, 2021. "Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program," Nature, Nature, vol. 590(7845), pages 290-299, February.
    3. Ernest Turro & William J. Astle & Karyn Megy & Stefan Gräf & Daniel Greene & Olga Shamardina & Hana Lango Allen & Alba Sanchis-Juan & Mattia Frontini & Chantal Thys & Jonathan Stephens & Rutendo Mapet, 2020. "Whole-genome sequencing of patients with rare diseases in a national health system," Nature, Nature, vol. 583(7814), pages 96-102, July.
    4. Joshua D. Backman & Alexander H. Li & Anthony Marcketta & Dylan Sun & Joelle Mbatchou & Michael D. Kessler & Christian Benner & Daren Liu & Adam E. Locke & Suganthi Balasubramanian & Ashish Yadav & Ni, 2021. "Exome sequencing and analysis of 454,787 UK Biobank participants," Nature, Nature, vol. 599(7886), pages 628-634, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Gareth Hawkes & Robin N. Beaumont & Zilin Li & Ravi Mandla & Xihao Li & Christine M. Albert & Donna K. Arnett & Allison E. Ashley-Koch & Aneel A. Ashrani & Kathleen C. Barnes & Eric Boerwinkle & Jenni, 2024. "Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Ghislain Rocheleau & Shoa L. Clarke & Gaëlle Auguste & Natalie R. Hasbani & Alanna C. Morrison & Adam S. Heath & Lawrence F. Bielak & Kruthika R. Iyer & Erica P. Young & Nathan O. Stitziel & Goo Jun &, 2024. "Rare variant contribution to the heritability of coronary artery disease," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Marsha M. Wheeler & Adrienne M. Stilp & Shuquan Rao & Bjarni V. Halldórsson & Doruk Beyter & Jia Wen & Anna V. Mihkaylova & Caitlin P. McHugh & John Lane & Min-Zhi Jiang & Laura M. Raffield & Goo Jun , 2022. "Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Vincent Michaud & Eulalie Lasseaux & David J. Green & Dave T. Gerrard & Claudio Plaisant & Tomas Fitzgerald & Ewan Birney & Benoît Arveiler & Graeme C. Black & Panagiotis I. Sergouniotis, 2022. "The contribution of common regulatory and protein-coding TYR variants to the genetic architecture of albinism," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    5. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Dick Schijven & Sourena Soheili-Nezhad & Simon E. Fisher & Clyde Francks, 2024. "Exome-wide analysis implicates rare protein-altering variants in human handedness," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    7. Sean A. Misek & Aaron Fultineer & Jeremie Kalfon & Javad Noorbakhsh & Isabella Boyle & Priyanka Roy & Joshua Dempster & Lia Petronio & Katherine Huang & Alham Saadat & Thomas Green & Adam Brown & John, 2024. "Germline variation contributes to false negatives in CRISPR-based experiments with varying burden across ancestries," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    8. Mit Shah & Marco H. A. Inácio & Chang Lu & Pierre-Raphaël Schiratti & Sean L. Zheng & Adam Clement & Antonio Marvao & Wenjia Bai & Andrew P. King & James S. Ware & Martin R. Wilkins & Johanna Mielke &, 2023. "Environmental and genetic predictors of human cardiovascular ageing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Mathias Seviiri & Matthew H. Law & Jue-Sheng Ong & Puya Gharahkhani & Pierre Fontanillas & Catherine M. Olsen & David C. Whiteman & Stuart MacGregor, 2022. "A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. Yash Pershad & Taralynn Mack & Hannah Poisner & Yasminka A. Jakubek & Adrienne M. Stilp & Braxton D. Mitchell & Joshua P. Lewis & Eric Boerwinkle & Ruth J. F. Loos & Nathalie Chami & Zhe Wang & Kathle, 2024. "Determinants of mosaic chromosomal alteration fitness," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    11. Elena V. Feofanova & Michael R. Brown & Taryn Alkis & Astrid M. Manuel & Xihao Li & Usman A. Tahir & Zilin Li & Kevin M. Mendez & Rachel S. Kelly & Qibin Qi & Han Chen & Martin G. Larson & Rozenn N. L, 2023. "Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    12. Matthew Tegtmeyer & Jatin Arora & Samira Asgari & Beth A. Cimini & Ajay Nadig & Emily Peirent & Dhara Liyanage & Gregory P. Way & Erin Weisbart & Aparna Nathan & Tiffany Amariuta & Kevin Eggan & Marzi, 2024. "High-dimensional phenotyping to define the genetic basis of cellular morphology," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    13. Erik Schoenmakers & Federica Marelli & Helle F. Jørgensen & W. Edward Visser & Carla Moran & Stefan Groeneweg & Carolina Avalos & Sean J. Jurgens & Nichola Figg & Alison Finigan & Neha Wali & Maura Ag, 2023. "Selenoprotein deficiency disorder predisposes to aortic aneurysm formation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Xiaoyi Raymond Gao & Marion Chiariglione & Alexander J. Arch, 2022. "Whole-exome sequencing study identifies rare variants and genes associated with intraocular pressure and glaucoma," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    15. Pei-Kuan Cong & Wei-Yang Bai & Jin-Chen Li & Meng-Yuan Yang & Saber Khederzadeh & Si-Rui Gai & Nan Li & Yu-Heng Liu & Shi-Hui Yu & Wei-Wei Zhao & Jun-Quan Liu & Yi Sun & Xiao-Wei Zhu & Pian-Pian Zhao , 2022. "Genomic analyses of 10,376 individuals in the Westlake BioBank for Chinese (WBBC) pilot project," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    16. Yu Chen & Amy Y. Wang & Courtney A. Barkley & Yixin Zhang & Xinyang Zhao & Min Gao & Mick D. Edmonds & Zechen Chong, 2023. "Deciphering the exact breakpoints of structural variations using long sequencing reads with DeBreak," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    17. Nazia Pathan & Wei Q. Deng & Matteo Di Scipio & Mohammad Khan & Shihong Mao & Robert W. Morton & Ricky Lali & Marie Pigeyre & Michael R. Chong & Guillaume Paré, 2024. "A method to estimate the contribution of rare coding variants to complex trait heritability," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    18. Naman S. Shetty & Mokshad Gaonkar & Nirav Patel & Akhil Pampana & Nehal Vekariya & Peng Li & Garima Arora & Pankaj Arora, 2024. "Determinants of transthyretin levels and their association with adverse clinical outcomes among UK Biobank participants," Nature Communications, Nature, vol. 15(1), pages 1-7, December.
    19. Aimee M. Deaton & Aditi Dubey & Lucas D. Ward & Peter Dornbos & Jason Flannick & Elaine Yee & Simina Ticau & Leila Noetzli & Margaret M. Parker & Rachel A. Hoffing & Carissa Willis & Mollie E. Plekan , 2022. "Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    20. Jennifer L. Halford & Valerie N. Morrill & Seung Hoan Choi & Sean J. Jurgens & Giorgio Melloni & Nicholas A. Marston & Lu-Chen Weng & Victor Nauffal & Amelia W. Hall & Sophia Gunn & Christina A. Austi, 2022. "Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30930-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.