LUSTR: a new customizable tool for calling genome-wide germline and somatic short tandem repeat variants
Authors: Lu Jinfeng , Toro Camilo , Adams David R. ,   Undiagnosed Diseases Network, Acosta Maria T. , Adam Margaret , Alvarez Raquel L. , Alvey Justin , Amendola Laura , Andrews Ashley , Ashley Euan A. , Bacino Carlos A. , Bademci Guney , Balasubramanyam Ashok , Baldridge Dustin , Bale Jim , Bamshad Michael , Barbouth Deborah , Bayrak-Toydemir Pinar , Beck Anita , Beggs Alan H. , Behrens Edward , Bejerano Gill , Bellen Hugo J. , Bennett Jimmy , Berg-Rood Beverly , Bernstein Jonathan A. , Berry Gerard T. , Bican Anna , Bivona Stephanie , Blue Elizabeth , Bohnsack John , Bonner Devon , Botto Lorenzo , Boyd Brenna , Briere Lauren C. , Brown Gabrielle , Burke Elizabeth A. , Burrage Lindsay C. , Butte Manish J. , Byers Peter , Byrd William E. , Carey John , Carrasquillo Olveen , Cassini Thomas , Chang Ta Chen Peter , Chanprasert Sirisak , Chao Hsiao-Tuan , Chinn Ivan , Clark Gary D. , Coakley Terra R. , Cobban Laurel A. , Cogan Joy D. , Coggins Matthew , Cole F. Sessions , Colley Heather A. , Cope Heidi , Corona Rosario , Craigen William J. , Crouse Andrew B. , Cunningham Michael , D’Souza Precilla , Dai Hongzheng , Dasari Surendra , Davis Joie , Dayal Jyoti G. , Dell’Angelica Esteban C. , Dickson Patricia , Dipple Katrina , Doherty Daniel , Dorrani Naghmeh , Doss Argenia L. , Douine Emilie D. , Earl Dawn , Eckstein David J. , Emrick Lisa T. , Eng Christine M. , Falk Marni , Fieg Elizabeth L. , Fisher Paul G. , Fogel Brent L. , Forghani Irman , Gahl William A. , Glass Ian , Gochuico Bernadette , Goddard Page C. , Godfrey Rena A. , Golden-Grant Katie , Grajewski Alana , Hadley Don , Hahn Sihoun , Halley Meghan C. , Hamid Rizwan , Hassey Kelly , Hayes Nichole , High Frances , Hing Anne , Hisama Fuki M. , Holm Ingrid A. , Hom Jason , Horike-Pyne Martha , Huang Alden , Hutchison Sarah , Introne Wendy , Isasi Rosario , Izumi Kosuke , Jamal Fariha , Jarvik Gail P. , Jarvik Jeffrey , Jayadev Suman , Jean-Marie Orpa , Jobanputra Vaidehi , Karaviti Lefkothea , Ketkar Shamika , Kiley Dana , Kilich Gonench , Kobren Shilpa N. , Kohane Isaac S. , Kohler Jennefer N. , Korrick Susan , Kozuira Mary , Krakow Deborah , Krasnewich Donna M. , Kravets Elijah , Lalani Seema R. , Lam Byron , Lam Christina , Lanpher Brendan C. , Lanza Ian R. , LeBlanc Kimberly , Lee Brendan H. , Levitt Roy , Lewis Richard A. , Liu Pengfei , Liu Xue Zhong , Longo Nicola , Loo Sandra K. , Loscalzo Joseph , Maas Richard L. , Macnamara Ellen F. , MacRae Calum A. , Maduro Valerie V. , Maghiro AudreyStephannie , Mahoney Rachel , Malicdan May Christine V. , Mamounas Laura A. , Manolio Teri A. , Mao Rong , Maravilla Kenneth , Marom Ronit , Marth Gabor , Martin Beth A. , Martin Martin G. , Martínez-Agosto Julian A. , Marwaha Shruti , McCauley Jacob , McConkie-Rosell Allyn , McCray Alexa T. , McGee Elisabeth , Mefford Heather , Merritt J. Lawrence , Might Matthew , Mirzaa Ghayda , Morava Eva , Moretti Paolo , Mulvihill John , Nakano-Okuno Mariko , Nelson Stanley F. , Newman John H. , Nicholas Sarah K. , Nickerson Deborah , Nieves-Rodriguez Shirley , Novacic Donna , Oglesbee Devin , Orengo James P. , Pace Laura , Pak Stephen , Pallais J. Carl , Palmer Christina G. S. , Papp Jeanette C. , Parker Neil H. , Phillips John A. , Posey Jennifer E. , Potocki Lorraine , Swerdzewski Barbara N. Pusey , Quinlan Aaron , Rao Deepak A. , Raper Anna , Raskind Wendy , Renteria Genecee , Reuter Chloe M. , Rives Lynette , Robertson Amy K. , Rodan Lance H. , Rosenfeld Jill A. , Rosenwasser Natalie , Rossignol Francis , Ruzhnikov Maura , Sacco Ralph , Sampson Jacinda B. , Saporta Mario , Schaechter Judy , Schedl Timothy , Schoch Kelly , Scott Daryl A. , Scott C. Ron , Seto Elaine , Shashi Vandana , Shin Jimann , Silverman Edwin K. , Sinsheimer Janet S. , Sisco Kathy , Smith Edward C. , Smith Kevin S. , Solnica-Krezel Lilianna , Solomon Ben , Spillmann Rebecca C. , Stoler Joan M. , Sullivan Kathleen , Sullivan Jennifer A. , Sun Angela , Sutton Shirley , Sweetser David A. , Sybert Virginia , Tabor Holly K. , Tan Queenie K.-G. , Tan Amelia L. M. , Tarakad Arjun , Tekin Mustafa , Telischi Fred , Thorson Willa , Tifft Cynthia J. , Tran Alyssa A. , Ungar Rachel A. , Urv Tiina K. , Vanderver Adeline , Velinder Matt , Viskochil Dave , Vogel Tiphanie P. , Wahl Colleen E. , Walker Melissa , Wallace Stephanie , Walley Nicole M. , Wambach Jennifer , Wan Jijun , Wang Lee-kai , Wangler Michael F. , Ward Patricia A. , Wegner Daniel , Hubshman Monika Weisz , Wener Mark , Wenger Tara , Westerfield Monte , Wheeler Matthew T. , Whitlock Jordan , Wolfe Lynne A. , Worley Kim , Xiao Changrui , Yamamoto Shinya , Yang John , Zhang Zhe , Zuchner Stephan , Moreno Cristiane Araujo Martins , Lee Wan-Ping , Leung Yuk Yee , Harms Mathew B. , Vardarajan Badri , Heinzen Erin L. 
Published: January 2024

Background

Short tandem repeats (STRs) are widely distributed across the human genome and are associated with numerous neurological disorders. However, the extent that STRs contribute to disease is likely under-estimated because of the challenges calling these variants in short read next generation sequencing data. Several computational tools have been developed for STR variant calling, but none fully address all of the complexities associated with this variant class.

Results

Here we introduce LUSTR which is designed to address some of the challenges associated with STR variant calling by enabling more flexibility in defining STR loci, allowing for customizable modules to tailor analyses, and expanding the capability to call somatic and multiallelic STR variants. LUSTR is a user-friendly and easily customizable tool for targeted or unbiased genome-wide STR variant screening that can use either predefined or novel genome builds. Using both simulated and real data sets, we demonstrated that LUSTR accurately infers germline and somatic STR expansions in individuals with and without diseases.

Conclusions

LUSTR offers a powerful and user-friendly approach that allows for the identification of STR variants and can facilitate more comprehensive studies evaluating the role of pathogenic STR variants across human diseases.