Abstract
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.
| Original language | English |
|---|---|
| Article number | 1300 |
| Journal | Scientific Reports |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Dec 2018 |
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In: Scientific Reports, Vol. 8, No. 1, 1300, 01.12.2018.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Telomerecat
T2 - A ploidy-agnostic method for estimating telomere length from whole genome sequencing data
AU - Farmery, James H.R.
AU - Smith, Mike L.
AU - Huissoon, Aarnoud
AU - Furnell, Abigail
AU - Mead, Adam
AU - Levine, Adam P.
AU - Manzur, Adnan
AU - Thrasher, Adrian
AU - Greenhalgh, Alan
AU - Parker, Alasdair
AU - Sanchis-Juan, Alba
AU - Richter, Alex
AU - Gardham, Alice
AU - Lawrie, Allan
AU - Sohal, Aman
AU - Creaser-Myers, Amanda
AU - Frary, Amy
AU - Greinacher, Andreas
AU - Themistocleous, Andreas
AU - Peacock, Andrew J.
AU - Marshall, Andrew
AU - Mumford, Andrew
AU - Rice, Andrew
AU - Webster, Andrew
AU - Brady, Angie
AU - Koziell, Ania
AU - Manson, Ania
AU - Chandra, Anita
AU - Hensiek, Anke
AU - Veld, Anna Huis In T.
AU - Maw, Anna
AU - Kelly, Anne M.
AU - Moore, Anthony
AU - Vonk Noordegraaf, Anton
AU - Attwood, Antony
AU - Herwadkar, Archana
AU - Ghofrani, Ardi
AU - Houweling, Arjan C.
AU - Girerd, Barbara
AU - Furie, Bruce
AU - Treacy, Carmen M.
AU - Millar, Carolyn M.
AU - Sewell, Carrock
AU - Roughley, Catherine
AU - Titterton, Catherine
AU - Williamson, Catherine
AU - Hadinnapola, Charaka
AU - Deshpande, Charu
AU - Toh, Cheng Hock
AU - Bacchelli, Chiara
AU - Patch, Chris
AU - Geet, Chris Van
AU - Babbs, Christian
AU - Bryson, Christine
AU - Penkett, Christopher J.
AU - Rhodes, Christopher J.
AU - Watt, Christopher
AU - Bethune, Claire
AU - Booth, Claire
AU - Lentaigne, Claire
AU - McJannet, Coleen
AU - Church, Colin
AU - French, Courtney
AU - Samarghitean, Crina
AU - Halmagyi, Csaba
AU - Gale, Daniel
AU - Greene, Daniel
AU - Hart, Daniel
AU - Allsup, David
AU - Bennett, David
AU - Edgar, David
AU - Kiely, David G.
AU - Gosal, David
AU - Perry, David J.
AU - Keeling, David
AU - Montani, David
AU - Shipley, Debbie
AU - Whitehorn, Deborah
AU - Fletcher, Debra
AU - Krishnakumar, Deepa
AU - Grozeva, Detelina
AU - Kumararatne, Dinakantha
AU - Thompson, Dorothy
AU - Josifova, Dragana
AU - Maher, Eamonn
AU - Wong, Edwin K.S.
AU - Murphy, Elaine
AU - Dewhurst, Eleanor
AU - Louka, Eleni
AU - Rosser, Elisabeth
AU - Chalmers, Elizabeth
AU - Colby, Elizabeth
AU - Drewe, Elizabeth
AU - McDermott, Elizabeth
AU - Thomas, Ellen
AU - Staples, Emily
AU - Clement, Emma
AU - Matthews, Emma
AU - Wakeling, Emma
AU - Oksenhendler, Eric
AU - Turro, Ernest
AU - Reid, Evan
AU - Wassmer, Evangeline
AU - Raymond, F. Lucy
AU - Hu, Fengyuan
AU - Kennedy, Fiona
AU - Soubrier, Florent
AU - Flinter, Frances
AU - Kovacs, Gabor
AU - Polwarth, Gary
AU - Ambegaonkar, Gautum
AU - Arno, Gavin
AU - Hudson, Gavin
AU - Woods, Geoff
AU - Coghlan, Gerry
AU - Hayman, Grant
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AU - Schotte, Gwen
AU - Cook, H. Terry
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AU - Schulze, Harald
AU - Boggard, Harm J.
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AU - Dolling, Helen
AU - Firth, Helen
AU - Gall, Henning
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AU - Markus, Hugh S.
AU - Watkins, Hugh
AU - Simeoni, Ilenia
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AU - Roberts, Irene
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AU - Gibbs, J. Simon R.
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AU - Whitworth, James
AU - Hurst, Jane
AU - Collins, Janine
AU - Suntharalingam, Jay
AU - Payne, Jeanette
AU - Thachil, Jecko
AU - Martin, Jennifer M.
AU - Carmichael, Jenny
AU - Maimaris, Jesmeen
AU - Paterson, Joan
AU - Pepke-Zaba, Joanna
AU - Heemskerk, Johan W.M.
AU - Gebhart, Johanna
AU - Davis, John
AU - Pasi, John
AU - Bradley, John R.
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AU - Stephens, Jonathan
AU - Rankin, Julia
AU - Anderson, Julie
AU - Vogt, Julie
AU - Von Ziegenweldt, Julie
AU - Rehnstrom, Karola
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AU - Peerlinck, Kathelijne
AU - Yates, Katherine
AU - Freson, Kathleen
AU - Stirrups, Kathleen
AU - Gomez, Keith
AU - Smith, Kenneth G.C.
AU - Rue-Albrecht, Kevin
AU - Gilmour, Kimberley
AU - Masati, Larahmie
AU - Scelsi, Laura
AU - Southgate, Laura
AU - Ranganathan, Lavanya
AU - Ginsberg, Lionel
AU - Devlin, Lisa
AU - Willcocks, Lisa
AU - Ormondroyd, Liz
AU - Lorenzo, Lorena
AU - Harper, Lorraine
AU - Allen, Louise
AU - Daugherty, Louise
AU - Chitre, Manali
AU - Kurian, Manju
AU - Humbert, Marc
AU - Tischkowitz, Marc
AU - Bitner-Glindzicz, Maria
AU - Erwood, Marie
AU - Scully, Marie
AU - Veltman, Marijke
AU - Caulfield, Mark
AU - Layton, Mark
AU - McCarthy, Mark
AU - Ponsford, Mark
AU - Toshner, Mark
AU - Bleda, Marta
AU - Wilkins, Martin
AU - Mathias, Mary
AU - Reilly, Mary
AU - Afzal, Maryam
AU - Brown, Matthew
AU - Rondina, Matthew
AU - Stubbs, Matthew
AU - Haimel, Matthias
AU - Lees, Melissa
AU - Laffan, Michael A.
AU - Browning, Michael
AU - Gattens, Michael
AU - Richards, Michael
AU - Michaelides, Michel
AU - Lambert, Michele P.
AU - Makris, Mike
AU - De Vries, Minka
AU - Mahdi-Rogers, Mohamed
AU - Saleem, Moin
AU - Thomas, Moira
AU - Holder, Muriel
AU - Eyries, Mélanie
AU - Clements-Brod, Naomi
AU - Canham, Natalie
AU - Dormand, Natalie
AU - Zuydam, Natalie Van
AU - Kingston, Nathalie
AU - Ghali, Neeti
AU - Cooper, Nichola
AU - Morrell, Nicholas W.
AU - Yeatman, Nigel
AU - Roy, Noémi
AU - Shamardina, Olga
AU - Alavijeh, Omid S.
AU - Gresele, Paolo
AU - Nurden, Paquita
AU - Chinnery, Patrick
AU - Deegan, Patrick
AU - Yong, Patrick
AU - Man, Patrick Yu Wai
AU - Corris, Paul A.
AU - Calleja, Paul
AU - Gissen, Paul
AU - Bolton-Maggs, Paula
AU - Rayner-Matthews, Paula
AU - Ghataorhe, Pavandeep K.
AU - Gordins, Pavel
AU - Stein, Penelope
AU - Collins, Peter
AU - Dixon, Peter
AU - Kelleher, Peter
AU - Ancliff, Phil
AU - Yu, Ping
AU - Tait, R. Campbell
AU - Linger, Rachel
AU - Doffinger, Rainer
AU - Machado, Rajiv
AU - Kazmi, Rashid
AU - Sargur, Ravishankar
AU - Favier, Remi
AU - Tan, Rhea
AU - Liesner, Ri
AU - Antrobus, Richard
AU - Sandford, Richard
AU - Scott, Richard
AU - Trembath, Richard
AU - Horvath, Rita
AU - Hadden, Rob
AU - Mackenzieross, Rob V.
AU - Henderson, Robert
AU - MacLaren, Robert
AU - James, Roger
AU - Ghurye, Rohit
AU - Dacosta, Rosa
AU - Hague, Rosie
AU - Mapeta, Rutendo
AU - Armstrong, Ruth
AU - Noorani, Sadia
AU - Murng, Sai
AU - Santra, Saikat
AU - Tuna, Salih
AU - Johnson, Sally
AU - Chong, Sam
AU - Lear, Sara
AU - Walker, Sara
AU - Goddard, Sarah
AU - Mangles, Sarah
AU - Westbury, Sarah
AU - Mehta, Sarju
AU - Hackett, Scott
AU - Nejentsev, Sergey
AU - Moledina, Shahin
AU - Bibi, Shahnaz
AU - Meehan, Sharon
AU - Othman, Shokri
AU - Revel-Vilk, Shoshana
AU - Holden, Simon
AU - McGowan, Simon
AU - Staines, Simon
AU - Savic, Sinisa
AU - Burns, Siobhan
AU - Grigoriadou, Sofia
AU - Papadia, Sofia
AU - Ashford, Sofie
AU - Schulman, Sol
AU - Ali, Sonia
AU - Park, Soo Mi
AU - Davies, Sophie
AU - Stock, Sophie
AU - Ali, Souad
AU - Deevi, Sri V.V.
AU - Gräf, Stefan
AU - Ghio, Stefano
AU - Wort, Stephen J.
AU - Jolles, Stephen
AU - Austin, Steve
AU - Welch, Steve
AU - Meacham, Stuart
AU - Rankin, Stuart
AU - Walker, Suellen
AU - Seneviratne, Suranjith
AU - Holder, Susan
AU - Sivapalaratnam, Suthesh
AU - Richardson, Sylvia
AU - Kuijpers, Taco W.
AU - Kuijpers, Taco W.
AU - Bariana, Tadbir K.
AU - Bakchoul, Tamam
AU - Everington, Tamara
AU - Renton, Tara
AU - Young, Tim
AU - Aitman, Timothy
AU - Warner, Timothy Q.
AU - Vale, Tom
AU - Hammerton, Tracey
AU - Pollock, Val
AU - Matser, Vera
AU - Cookson, Victoria
AU - Clowes, Virginia
AU - Qasim, Waseem
AU - Wei, Wei
AU - Erber, Wendy N.
AU - Ouwehand, Willem H.
AU - Astle, William
AU - Egner, William
AU - Turek, Wojciech
AU - Henskens, Yvonne
AU - Tan, Yvonne
AU - Lynch, Andy G.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85040985054&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-14403-y
DO - 10.1038/s41598-017-14403-y
M3 - Article
C2 - 29358629
AN - SCOPUS:85040985054
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 1300
ER -