LUSTR: a new customizable tool for calling genome-wide germline and somatic short tandem repeat variants
Abstract 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 ge...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
|
| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12864-023-09935-9 |
| _version_ | 1797340263914405888 |
|---|---|
| author | Jinfeng Lu Camilo Toro David R. Adams Undiagnosed Diseases Network Cristiane Araujo Martins Moreno Wan-Ping Lee Yuk Yee Leung Mathew B. Harms Badri Vardarajan Erin L. Heinzen |
| author_facet | Jinfeng Lu Camilo Toro David R. Adams Undiagnosed Diseases Network Cristiane Araujo Martins Moreno Wan-Ping Lee Yuk Yee Leung Mathew B. Harms Badri Vardarajan Erin L. Heinzen |
| author_sort | Jinfeng Lu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-08T10:00:29Z |
| format | Article |
| id | doaj.art-10f83745c1f7435fb5ac3dd6aa04ee9f |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-03-08T10:00:29Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-10f83745c1f7435fb5ac3dd6aa04ee9f2024-01-29T10:59:47ZengBMCBMC Genomics1471-21642024-01-0125112210.1186/s12864-023-09935-9LUSTR: a new customizable tool for calling genome-wide germline and somatic short tandem repeat variantsJinfeng Lu0Camilo Toro1David R. Adams2Undiagnosed Diseases Network3Cristiane Araujo Martins Moreno4Wan-Ping Lee5Yuk Yee Leung6Mathew B. Harms7Badri Vardarajan8Erin L. Heinzen9Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel HillNIH Undiagnosed Diseases Program, National Human Genome Research Institute (NHGRI), National Institutes of HealthNIH Undiagnosed Diseases Program, National Human Genome Research Institute (NHGRI), National Institutes of HealthNIH Undiagnosed Diseases Program, National Human Genome Research Institute (NHGRI), National Institutes of HealthNeurology Department, Universidade de São PauloPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory MedicinePerelman School of Medicine, University of PennsylvaniaPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory MedicinePerelman School of Medicine, University of PennsylvaniaDepartment of Neurology, Division of Neuromuscular Medicine, Columbia University Irving Medical CenterThe Taub Institute for Research On Alzheimer’s Disease and the Aging Brain, Gertrude H. Sergievsky Center, Department of Neurology, College of Physicians and Surgeons, Columbia University, The New York Presbyterian HospitalDivision of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel HillAbstract 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.https://doi.org/10.1186/s12864-023-09935-9Short tandem repeatsBioinformaticsVariant calling tool kitSomaticLUSTR |
| spellingShingle | Jinfeng Lu Camilo Toro David R. Adams Undiagnosed Diseases Network Cristiane Araujo Martins Moreno Wan-Ping Lee Yuk Yee Leung Mathew B. Harms Badri Vardarajan Erin L. Heinzen LUSTR: a new customizable tool for calling genome-wide germline and somatic short tandem repeat variants BMC Genomics Short tandem repeats Bioinformatics Variant calling tool kit Somatic LUSTR |
| title | LUSTR: a new customizable tool for calling genome-wide germline and somatic short tandem repeat variants |
| title_full | LUSTR: a new customizable tool for calling genome-wide germline and somatic short tandem repeat variants |
| title_fullStr | LUSTR: a new customizable tool for calling genome-wide germline and somatic short tandem repeat variants |
| title_full_unstemmed | LUSTR: a new customizable tool for calling genome-wide germline and somatic short tandem repeat variants |
| title_short | LUSTR: a new customizable tool for calling genome-wide germline and somatic short tandem repeat variants |
| title_sort | lustr a new customizable tool for calling genome wide germline and somatic short tandem repeat variants |
| topic | Short tandem repeats Bioinformatics Variant calling tool kit Somatic LUSTR |
| url | https://doi.org/10.1186/s12864-023-09935-9 |
| work_keys_str_mv | AT jinfenglu lustranewcustomizabletoolforcallinggenomewidegermlineandsomaticshorttandemrepeatvariants AT camilotoro lustranewcustomizabletoolforcallinggenomewidegermlineandsomaticshorttandemrepeatvariants AT davidradams lustranewcustomizabletoolforcallinggenomewidegermlineandsomaticshorttandemrepeatvariants AT undiagnoseddiseasesnetwork lustranewcustomizabletoolforcallinggenomewidegermlineandsomaticshorttandemrepeatvariants AT cristianearaujomartinsmoreno lustranewcustomizabletoolforcallinggenomewidegermlineandsomaticshorttandemrepeatvariants AT wanpinglee lustranewcustomizabletoolforcallinggenomewidegermlineandsomaticshorttandemrepeatvariants AT yukyeeleung lustranewcustomizabletoolforcallinggenomewidegermlineandsomaticshorttandemrepeatvariants AT mathewbharms lustranewcustomizabletoolforcallinggenomewidegermlineandsomaticshorttandemrepeatvariants AT badrivardarajan lustranewcustomizabletoolforcallinggenomewidegermlineandsomaticshorttandemrepeatvariants AT erinlheinzen lustranewcustomizabletoolforcallinggenomewidegermlineandsomaticshorttandemrepeatvariants |