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

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.