Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data

Authors: James H. R. Farmery, Mike L. Smith, NIHR BioResource - Rare Diseases, Aarnoud Huissoon, Abigail Furnell, Adam J. Mead, Adam P. Levine, Adnan Manzur, Adrian J. Thrasher, Alan Greenhalgh, Alasdair Parker, Alba Sanchis-Juan, Alex Richter, Alice Gardham, Allan Lawrie, Aman Sohal, Amanda Creaser-Myers, Amy Frary, Andreas Greinacher, Andreas C. Themistocleous, Andrew J. Peacock, Andrew Marshall, Andrew Mumford, Andrew J. Rice, Andrew Webster, Angie Brady, Ania Koziell, Ania Manson, Anita Chandra, Anke Hensiek, Anna Huis in’t Veld, Anna Maw, Anne M. Kelly, Anthony T. Moore, Anton Vonk Noordegraaf, Antony Attwood, Archana Herwadkar, Ardi Ghofrani, Arjan C. Houweling, Barbara Girerd, Bruce Furie, Carmen Treacy, Carolyn M. Millar, Carrock Sewell, Catherine Roughley, Catherine Titterton, Catherine Williamson, Charaka Hadinnapola, Charu Deshpande, Cheng‐Hock Toh, Chiara Bacchelli, Christine Patch, Chris Van Geet, Christian Babbs, Christine Bryson, Christopher J. Penkett, Christopher J. Rhodes, C. Ian F. Watt, Claire Bethune, Claire Booth, Claire Lentaigne, Coleen McJannet, Colin Church, Courtney E. French, Crina Samarghitean, Csaba Halmagyi, Daniel P. Gale, Daniel Greene, Daniel P. Hart, David Allsup, David Bennett, David Edgar, David G. Kiely, David Gosal, David J. Perry, David Keeling, David Montani, Debbie Shipley, Deborah Whitehorn, Debra Fletcher, Deepa Krishnakumar, Detelina Grozeva, Dinakantha Kumararatne, Dorothy Thompson, Dragana Josifova, Eamonn R. Maher, Edwin Wong, Elaine Murphy, Eleanor Dewhurst, Eleni Louka, Elisabeth Rosser, Elizabeth Chalmers, Elizabeth Colby, Elizabeth Drewe, Elizabeth McDermott, Ellen Thomas, Emily Staples, Emma Clement, Emma Matthews, Emma Wakeling, Éric Oksenhendler, Ernest Turro, Evan Reid, Evangeline Wassmer, F. Lucy Raymond, Fengyuan Hu, Fiona Kennedy, Florent Soubrier, Frances Flinter, Gábor Kovács, Gary Polwarth, Gautum Ambegaonkar, Gavin Arno, Gavin Hudson, Geoff Woods, Gerry Coghlan, Grant Hayman, Gururaj Arumugakani, Gwen Schotte, H. Terry Cook, Hana Alachkar, Hana Lango Allen, Hana Lango Allen, Hannah Stark, Hans J. Stauss, Harald Schulze, Harm Boggard, Helen Baxendale, Helen Dolling, Helen V. Firth, Henning Gall, Henry G. Watson, Hilary Longhurst, Hugh S. Markus, Hugh Watkins, Ilenia Simeoni, Ingrid Emmerson, Irene Roberts, Isabella Quinti, Ivy Wanjiku, J. Simon R. Gibbs, James Thaventhiran, James W. Whitworth, Jane A. Hurst, Janine Collins, Jay Suntharalingam, Jeanette Payne, Jecko Thachil, Jennifer M. Martin, Jennifer M. Martin, Jenny Carmichael, Jesmeen Maimaris, Joan Paterson, Joanna Pepke‐Żaba, Johan W. M. Heemskerk, Johanna Gebhart, John Davis, John Pasi, John R. Bradley, John Wharton, Jonathan Stephens, Julia Rankin, Julie Anderson, Julie Vogt, Julie von Ziegenweldt, Karola Rehnström, Karyn Mégy, Kate Talks, Kathelijne Peerlinck, Katherine Yates, Kathleen Freson, Kathleen Stirrups, Keith Gomez, Kenneth G. C. Smith, Keren Carss, Kévin Rue-Albrecht, Kimberly Gilmour, Larahmie Masati, Laura Scelsi, Laura Southgate, Lavanya Ranganathan, Lionel Ginsberg, Lisa Devlin, Lisa Willcocks, Elizabeth Ormondroyd, Lorena Lorenzo, Lorraine Harper, Louise Allen, Louise C. Daugherty, Manali Chitre, Manju A. Kurian, Marc Humbert, Marc Tischkowitz, Maria Bitner‐Glindzicz, Marie Erwood, Marie Scully, Marijke Veltman, Mark J. Caulfield, Mark Layton, Mark I. McCarthy, Mark Ponsford, Mark Toshner, Marta Bleda, Martin Wilkins, Mary Mathias, Mary M. Reilly, Maryam Afzal, Matthew Brown, Matthew T. Rondina, Matthew Stubbs, Matthias Haimel, Melissa Lees, Michael Laffan, Michael J. Browning, Michael Gattens, Michael J. Richards, Michel Michaelides, Michele P. Lambert, Mike Makris, Minka De Vries, Mohamed Mahdi‐Rogers, Moin A. Saleem, Moira Thomas, Muriel Holder, Mélanie Eyries, Emma Clement, Natalie Canham, Natalie Dormand, Natalie Van Zuydam, Nathalie Kingston, Neeti Ghali, Nichola Cooper, Nicholas W. Morrell, Nigel Yeatman, Noémi Roy, Olga Shamardina, Omid S. Alavijeh, Paolo Gresele, Paquita Nurden, Patrick F. Chinnery, Patrick Deegan, Patrick Yong, Patrick Yu‐Wai‐Man, Paul A. Corris, Paul Calleja, Paul Gissen, Paula Bolton‐Maggs, Paula Rayner-Matthews, Pavandeep Ghataorhe, Pavel Gordins, Penelope E. Stein, Peter L. Collins, Peter Dixon, Peter Kelleher, Phil Ancliff, Ping Yu, R. Campbell Tait, Rachel Linger, Rainer Döffinger, Rajiv D. Machado, Rashid Kazmi, Ravishankar Sargur, Rémi Favier, Rhea Tan, Ri Liesner, Richard Antrobus, Richard Sandford, Richard Scott, Richard C. Trembath, Rita Horváth, Robert D. M. Hadden, Rob V. MackenzieRoss, Robert Henderson, Robert E. MacLaren, Roger James, Rohit Ghurye, Rosa DaCosta, Rosie Hague, Rutendo Mapeta, Ruth Armstrong, Sadia Noorani, Sai Murng, Saikat Santra, Salih Tuna, Sally Johnson, Sam Chong, Sara Lear, Sara J. Walker, Sarah Goddard, Sarah Mangles, Sarah K. Westbury, Sarju Mehta, Scott Hackett, Sergey Nejentsev, Shahin Moledina, Shahnaz Bibi, Sharon Meehan, Shokri Othman, Shoshana Revel‐Vilk, Simon Holden, Simon J. McGowan, Simon Staines, Sinisa Savic, Siobhan O. Burns, Sofia Grigoriadou, Sofia Papadia, Sofie Ashford, Sol Schulman, Sonia Ali, Soo‐Mi Park, Sophie Davies, Sophie Stock, Souad Ali, Sri V. V. Deevi, Stefan Gräf, Stefano Ghio, Stephen J. Wort, Stephen Jolles, Steve Austin, Steve Welch, Stuart Meacham, Stuart Rankin, Suellen M. Walker, Suranjith L. Seneviratne, Susan Holder, Suthesh Sivapalaratnam, Sylvia Richardson, Taco W. Kuijpers, Taco W. Kuijpers, Tadbir K. Bariana, Tamam Bakchoul, Tamara Everington, Tara Renton, Tim Young, Timothy J. Aitman, Timothy Q. Warner, Tom Vale, Tracey Hammerton, Val Pollock, Vera Matser, Victoria Cookson, Virginia Clowes, Waseem Qasim, Wei Wei, Wendy N. Erber, Willem H. Ouwehand, William J. Astle, William Egner, Wojciech Turek, Yvonne Henskens, Yvonne Tan, Andy G. Lynch - Scientific Reports 2018 cited by 90

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype.