Yasminka A Jakubek1, F Anthony San Lucas1,2, Paul Scheet1. 1. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 2. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract
MOTIVATION: Genetic analysis of cancer regularly includes two or more samples from the same patient. Somatic copy number alterations leading to allelic imbalance (AI) play a critical role in cancer initiation and progression. Directional analysis and visualization of the alleles in imbalance in multi-sample settings allow for inference of recurrent mutations, providing insights into mutation rates, clonality and the genomic architecture and etiology of cancer. RESULTS: The REpeat Chromosomal changes Uncovered by Reflection (RECUR) is an R application for the comparative analysis of AI profiles derived from SNP array and next-generation sequencing data. The algorithm accepts genotype calls and 'B allele' frequencies (BAFs) from at least two samples derived from the same individual. For a predefined set of genomic regions with AI, RECUR compares BAF values among samples. In the presence of AI, the expected value of a BAF can shift in two possible directions, reflecting an increased or decreased abundance of the maternal haplotype, relative to the paternal. The phenomenon of opposite haplotype shifts, or 'mirrored subclonal allelic imbalance', is a form of heterogeneity, and has been linked to clinico-pathological features of cancer. RECUR detects such genomic segments of opposite haplotypes in imbalance and plots BAF values for all samples, using a two-color scheme for intuitive visualization. AVAILABILITY AND IMPLEMENTATION: RECUR is available as an R application. Source code and documentation are available at scheet.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: Genetic analysis of cancer regularly includes two or more samples from the same patient. Somatic copy number alterations leading to allelic imbalance (AI) play a critical role in cancer initiation and progression. Directional analysis and visualization of the alleles in imbalance in multi-sample settings allow for inference of recurrent mutations, providing insights into mutation rates, clonality and the genomic architecture and etiology of cancer. RESULTS: The REpeat Chromosomal changes Uncovered by Reflection (RECUR) is an R application for the comparative analysis of AI profiles derived from SNP array and next-generation sequencing data. The algorithm accepts genotype calls and 'B allele' frequencies (BAFs) from at least two samples derived from the same individual. For a predefined set of genomic regions with AI, RECUR compares BAF values among samples. In the presence of AI, the expected value of a BAF can shift in two possible directions, reflecting an increased or decreased abundance of the maternal haplotype, relative to the paternal. The phenomenon of opposite haplotype shifts, or 'mirrored subclonal allelic imbalance', is a form of heterogeneity, and has been linked to clinico-pathological features of cancer. RECUR detects such genomic segments of opposite haplotypes in imbalance and plots BAF values for all samples, using a two-color scheme for intuitive visualization. AVAILABILITY AND IMPLEMENTATION: RECUR is available as an R application. Source code and documentation are available at scheet.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Adam B Olshen; Henrik Bengtsson; Pierre Neuvial; Paul T Spellman; Richard A Olshen; Venkatraman E Seshan Journal: Bioinformatics Date: 2011-06-11 Impact factor: 6.937
Authors: Yasminka Jakubek; Wenhua Lang; Selina Vattathil; Melinda Garcia; Li Xu; Lili Huang; Suk-Young Yoo; Li Shen; Wei Lu; Chi-Wan Chow; Zachary Weber; Gareth Davies; Jing Huang; Carmen Behrens; Neda Kalhor; Cesar Moran; Junya Fujimoto; Reza Mehran; Randa El-Zein; Stephen G Swisher; Jing Wang; Jerry Fowler; Avrum E Spira; Erik A Ehli; Ignacio I Wistuba; Paul Scheet; Humam Kadara Journal: Cancer Res Date: 2016-05-23 Impact factor: 12.701
Authors: Mariam Jamal-Hanjani; Gareth A Wilson; Nicholas McGranahan; Nicolai J Birkbak; Thomas B K Watkins; Selvaraju Veeriah; Seema Shafi; Diana H Johnson; Richard Mitter; Rachel Rosenthal; Max Salm; Stuart Horswell; Mickael Escudero; Nik Matthews; Andrew Rowan; Tim Chambers; David A Moore; Samra Turajlic; Hang Xu; Siow-Ming Lee; Martin D Forster; Tanya Ahmad; Crispin T Hiley; Christopher Abbosh; Mary Falzon; Elaine Borg; Teresa Marafioti; David Lawrence; Martin Hayward; Shyam Kolvekar; Nikolaos Panagiotopoulos; Sam M Janes; Ricky Thakrar; Asia Ahmed; Fiona Blackhall; Yvonne Summers; Rajesh Shah; Leena Joseph; Anne M Quinn; Phil A Crosbie; Babu Naidu; Gary Middleton; Gerald Langman; Simon Trotter; Marianne Nicolson; Hardy Remmen; Keith Kerr; Mahendran Chetty; Lesley Gomersall; Dean A Fennell; Apostolos Nakas; Sridhar Rathinam; Girija Anand; Sajid Khan; Peter Russell; Veni Ezhil; Babikir Ismail; Melanie Irvin-Sellers; Vineet Prakash; Jason F Lester; Malgorzata Kornaszewska; Richard Attanoos; Haydn Adams; Helen Davies; Stefan Dentro; Philippe Taniere; Brendan O'Sullivan; Helen L Lowe; John A Hartley; Natasha Iles; Harriet Bell; Yenting Ngai; Jacqui A Shaw; Javier Herrero; Zoltan Szallasi; Roland F Schwarz; Aengus Stewart; Sergio A Quezada; John Le Quesne; Peter Van Loo; Caroline Dive; Allan Hackshaw; Charles Swanton Journal: N Engl J Med Date: 2017-04-26 Impact factor: 91.245
Authors: Juan R González; Benjamín Rodríguez-Santiago; Alejandro Cáceres; Roger Pique-Regi; Nathaniel Rothman; Stephen J Chanock; Lluís Armengol; Luis A Pérez-Jurado Journal: BMC Bioinformatics Date: 2011-05-17 Impact factor: 3.169
Authors: Samra Turajlic; Hang Xu; Kevin Litchfield; Andrew Rowan; Tim Chambers; Jose I Lopez; David Nicol; Tim O'Brien; James Larkin; Stuart Horswell; Mark Stares; Lewis Au; Mariam Jamal-Hanjani; Ben Challacombe; Ashish Chandra; Steve Hazell; Claudia Eichler-Jonsson; Aspasia Soultati; Simon Chowdhury; Sarah Rudman; Joanna Lynch; Archana Fernando; Gordon Stamp; Emma Nye; Faiz Jabbar; Lavinia Spain; Sharanpreet Lall; Rosa Guarch; Mary Falzon; Ian Proctor; Lisa Pickering; Martin Gore; Thomas B K Watkins; Sophia Ward; Aengus Stewart; Renzo DiNatale; Maria F Becerra; Ed Reznik; James J Hsieh; Todd A Richmond; George F Mayhew; Samantha M Hill; Catherine D McNally; Carol Jones; Heidi Rosenbaum; Stacey Stanislaw; Daniel L Burgess; Nelson R Alexander; Charles Swanton Journal: Cell Date: 2018-04-12 Impact factor: 41.582
Authors: Johan Staaf; David Lindgren; Johan Vallon-Christersson; Anders Isaksson; Hanna Göransson; Gunnar Juliusson; Richard Rosenquist; Mattias Höglund; Ake Borg; Markus Ringnér Journal: Genome Biol Date: 2008-09-16 Impact factor: 13.583
Authors: F Anthony San Lucas; Smruthy Sivakumar; Selina Vattathil; Jerry Fowler; Eduardo Vilar; Paul Scheet Journal: Bioinformatics Date: 2016-06-10 Impact factor: 6.937
Authors: Sasi Arunachalam; Karol Szlachta; Samuel W Brady; Xiaotu Ma; Bensheng Ju; Bridget Shaner; Heather L Mulder; John Easton; Benjamin J Raphael; Matthew Myers; Christopher Tinkle; Sariah J Allen; Brent A Orr; Cynthia J Wetmore; Suzanne J Baker; Jinghui Zhang Journal: Acta Neuropathol Commun Date: 2022-05-31 Impact factor: 7.578
Authors: Smruthy Sivakumar; F Anthony San Lucas; Yasminka A Jakubek; Tina L McDowell; Wenhua Lang; Noah Kallsen; Shanna Peyton; Gareth E Davies; Junya Fukuoka; Yasushi Yatabe; Jianjun Zhang; P Andrew Futreal; Jerry Fowler; Junya Fujimoto; Erik A Ehli; Ernest T Hawk; Ignacio I Wistuba; Humam Kadara; Paul Scheet Journal: EBioMedicine Date: 2019-03-21 Impact factor: 8.143