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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.

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Digital Access to Scholarship at Harvard  

Autor(es)

Farmery, James H. R. -  Smith, Mike L. -  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 -  Man, Patrick Yu Wai -  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. - 

Id.: 71030421

Idioma: inglés (Estados Unidos)  - 

Versión: 1.0

Estado: Final

Tipo de recurso: Journal Article  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

: open

Requerimientos técnicos:  Browser: Any - 

Relación: [References] doi:10.1038/s41598-017-14403-y
[References] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778012/pdf/
[References] Scientific Reports

Fecha de contribución: 28-feb-2018

Contacto:

Localización:
* Farmery, J. H. R., M. L. Smith, A. Huissoon, A. Furnell, A. Mead, A. P. Levine, A. Manzur, et al. 2018. “Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.” Scientific Reports 8 (1): 1300. doi:10.1038/s41598-017-14403-y. http://dx.doi.org/10.1038/s41598-017-14403-y.

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