PtWAVE: a high-sensitive deconvolution software of sequencing trace for the detection of large indels in genome editing
Abstract Background Tracking of Insertions and DEletions (TIDE) analysis, which computationally deconvolves capillary sequencing data derived from the DNA of bulk or clonal cell populations to estimate the efficiency of targeted mutagenesis by programmable nucleases, has played a significant role in...
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BMC
2025-04-01
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| Series: | BMC Bioinformatics |
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| Online Access: | https://doi.org/10.1186/s12859-025-06139-8 |
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| author | Kazuki Nakamae Saya Ide Nagaki Ohnuki Yoshiko Nakagawa Keisuke Okuhara Hidemasa Bono |
| author_facet | Kazuki Nakamae Saya Ide Nagaki Ohnuki Yoshiko Nakagawa Keisuke Okuhara Hidemasa Bono |
| author_sort | Kazuki Nakamae |
| collection | DOAJ |
| description | Abstract Background Tracking of Insertions and DEletions (TIDE) analysis, which computationally deconvolves capillary sequencing data derived from the DNA of bulk or clonal cell populations to estimate the efficiency of targeted mutagenesis by programmable nucleases, has played a significant role in the field of genome editing. However, the detection range covered by conventional TIDE analysis is limited. Range extension for deconvolution is required to detect larger deletions and insertions (indels) derived from genome editing in TIDE analysis. However, extending the deconvolution range introduces uncertainty into the deconvolution process. Moreover, the accuracy and sensitivity of TIDE analysis tools for large deletions (> 50 bp) remain poorly understood. Results In this study, we introduced a new software called PtWAVE that can detect a wide range of indel sizes, up to 200 bp. PtWAVE also offers options for variable selection and fitting algorithms to prevent uncertainties in the model. We evaluated the performance of PtWAVE by using in vitro capillary sequencing data that mimicked DNA sequencing, including large deletions. Furthermore, we confirmed that PtWAVE can stably analyze trace sequencing data derived from actual genome-edited samples. Conclusions PtWAVE demonstrated superior accuracy and sensitivity compared to the existing TIDE analysis tools for DNA samples, including large deletions. PtWAVE can accelerate genome editing applications in organisms and cell types in which large deletions often occur when programmable nucleases are applied. |
| format | Article |
| id | doaj-art-b841b4fa9ccc4b8c8df03ed2180b68e1 |
| institution | OA Journals |
| issn | 1471-2105 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | BMC Bioinformatics |
| spelling | doaj-art-b841b4fa9ccc4b8c8df03ed2180b68e12025-08-20T02:10:53ZengBMCBMC Bioinformatics1471-21052025-04-0126111710.1186/s12859-025-06139-8PtWAVE: a high-sensitive deconvolution software of sequencing trace for the detection of large indels in genome editingKazuki Nakamae0Saya Ide1Nagaki Ohnuki2Yoshiko Nakagawa3Keisuke Okuhara4Hidemasa Bono5Genome Editing Innovation Center, Hiroshima UniversityGenome Editing Innovation Center, Hiroshima UniversityGenome Editing Innovation Center, Hiroshima UniversityPtBio Inc.PtBio Inc.Genome Editing Innovation Center, Hiroshima UniversityAbstract Background Tracking of Insertions and DEletions (TIDE) analysis, which computationally deconvolves capillary sequencing data derived from the DNA of bulk or clonal cell populations to estimate the efficiency of targeted mutagenesis by programmable nucleases, has played a significant role in the field of genome editing. However, the detection range covered by conventional TIDE analysis is limited. Range extension for deconvolution is required to detect larger deletions and insertions (indels) derived from genome editing in TIDE analysis. However, extending the deconvolution range introduces uncertainty into the deconvolution process. Moreover, the accuracy and sensitivity of TIDE analysis tools for large deletions (> 50 bp) remain poorly understood. Results In this study, we introduced a new software called PtWAVE that can detect a wide range of indel sizes, up to 200 bp. PtWAVE also offers options for variable selection and fitting algorithms to prevent uncertainties in the model. We evaluated the performance of PtWAVE by using in vitro capillary sequencing data that mimicked DNA sequencing, including large deletions. Furthermore, we confirmed that PtWAVE can stably analyze trace sequencing data derived from actual genome-edited samples. Conclusions PtWAVE demonstrated superior accuracy and sensitivity compared to the existing TIDE analysis tools for DNA samples, including large deletions. PtWAVE can accelerate genome editing applications in organisms and cell types in which large deletions often occur when programmable nucleases are applied.https://doi.org/10.1186/s12859-025-06139-8CRISPRGenome editingIndel analysisGUI softwareTIDE analysis |
| spellingShingle | Kazuki Nakamae Saya Ide Nagaki Ohnuki Yoshiko Nakagawa Keisuke Okuhara Hidemasa Bono PtWAVE: a high-sensitive deconvolution software of sequencing trace for the detection of large indels in genome editing BMC Bioinformatics CRISPR Genome editing Indel analysis GUI software TIDE analysis |
| title | PtWAVE: a high-sensitive deconvolution software of sequencing trace for the detection of large indels in genome editing |
| title_full | PtWAVE: a high-sensitive deconvolution software of sequencing trace for the detection of large indels in genome editing |
| title_fullStr | PtWAVE: a high-sensitive deconvolution software of sequencing trace for the detection of large indels in genome editing |
| title_full_unstemmed | PtWAVE: a high-sensitive deconvolution software of sequencing trace for the detection of large indels in genome editing |
| title_short | PtWAVE: a high-sensitive deconvolution software of sequencing trace for the detection of large indels in genome editing |
| title_sort | ptwave a high sensitive deconvolution software of sequencing trace for the detection of large indels in genome editing |
| topic | CRISPR Genome editing Indel analysis GUI software TIDE analysis |
| url | https://doi.org/10.1186/s12859-025-06139-8 |
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