Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers
Abstract Background Recently, copy number variations (CNV) impacting genes involved in oncogenic pathways have attracted an increasing attention to manage disease susceptibility. CNV is one of the most important somatic aberrations in the genome of tumor cells. Oncogene activation and tumor suppress...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | BMC Bioinformatics |
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| Online Access: | https://doi.org/10.1186/s12859-021-04060-4 |
| _version_ | 1829521179858173952 |
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| author | Pierre-Julien Viailly Vincent Sater Mathieu Viennot Elodie Bohers Nicolas Vergne Caroline Berard Hélène Dauchel Thierry Lecroq Alison Celebi Philippe Ruminy Vinciane Marchand Marie-Delphine Lanic Sydney Dubois Dominique Penther Hervé Tilly Sylvain Mareschal Fabrice Jardin |
| author_facet | Pierre-Julien Viailly Vincent Sater Mathieu Viennot Elodie Bohers Nicolas Vergne Caroline Berard Hélène Dauchel Thierry Lecroq Alison Celebi Philippe Ruminy Vinciane Marchand Marie-Delphine Lanic Sydney Dubois Dominique Penther Hervé Tilly Sylvain Mareschal Fabrice Jardin |
| author_sort | Pierre-Julien Viailly |
| collection | DOAJ |
| description | Abstract Background Recently, copy number variations (CNV) impacting genes involved in oncogenic pathways have attracted an increasing attention to manage disease susceptibility. CNV is one of the most important somatic aberrations in the genome of tumor cells. Oncogene activation and tumor suppressor gene inactivation are often attributed to copy number gain/amplification or deletion, respectively, in many cancer types and stages. Recent advances in next generation sequencing protocols allow for the addition of unique molecular identifiers (UMI) to each read. Each targeted DNA fragment is labeled with a unique random nucleotide sequence added to sequencing primers. UMI are especially useful for CNV detection by making each DNA molecule in a population of reads distinct. Results Here, we present molecular Copy Number Alteration (mCNA), a new methodology allowing the detection of copy number changes using UMI. The algorithm is composed of four main steps: the construction of UMI count matrices, the use of control samples to construct a pseudo-reference, the computation of log-ratios, the segmentation and finally the statistical inference of abnormal segmented breaks. We demonstrate the success of mCNA on a dataset of patients suffering from Diffuse Large B-cell Lymphoma and we highlight that mCNA results have a strong correlation with comparative genomic hybridization. Conclusion We provide mCNA, a new approach for CNV detection, freely available at https://gitlab.com/pierrejulien.viailly/mcna/ under MIT license. mCNA can significantly improve detection accuracy of CNV changes by using UMI. |
| first_indexed | 2024-12-16T15:10:53Z |
| format | Article |
| id | doaj.art-b229cd4e14c749a68bcf4b30c189122a |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-16T15:10:53Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-b229cd4e14c749a68bcf4b30c189122a2022-12-21T22:26:58ZengBMCBMC Bioinformatics1471-21052021-03-0122111510.1186/s12859-021-04060-4Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiersPierre-Julien Viailly0Vincent Sater1Mathieu Viennot2Elodie Bohers3Nicolas Vergne4Caroline Berard5Hélène Dauchel6Thierry Lecroq7Alison Celebi8Philippe Ruminy9Vinciane Marchand10Marie-Delphine Lanic11Sydney Dubois12Dominique Penther13Hervé Tilly14Sylvain Mareschal15Fabrice Jardin16INSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENLMRS UMRS 6085, Normandie Univ, UNIROUENLITIS EA 4108, Normandie Univ, UNIROUENLITIS EA 4108, Normandie Univ, UNIROUENLITIS EA 4108, Normandie Univ, UNIROUENINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENINSERM U1052 UMR CNRS 5286, Cancer Research Center of LyonINSERM U1245, Team Genomics and Biomarkers of Lymphoma and Solid Tumors, Normandie Univ, UNIROUENAbstract Background Recently, copy number variations (CNV) impacting genes involved in oncogenic pathways have attracted an increasing attention to manage disease susceptibility. CNV is one of the most important somatic aberrations in the genome of tumor cells. Oncogene activation and tumor suppressor gene inactivation are often attributed to copy number gain/amplification or deletion, respectively, in many cancer types and stages. Recent advances in next generation sequencing protocols allow for the addition of unique molecular identifiers (UMI) to each read. Each targeted DNA fragment is labeled with a unique random nucleotide sequence added to sequencing primers. UMI are especially useful for CNV detection by making each DNA molecule in a population of reads distinct. Results Here, we present molecular Copy Number Alteration (mCNA), a new methodology allowing the detection of copy number changes using UMI. The algorithm is composed of four main steps: the construction of UMI count matrices, the use of control samples to construct a pseudo-reference, the computation of log-ratios, the segmentation and finally the statistical inference of abnormal segmented breaks. We demonstrate the success of mCNA on a dataset of patients suffering from Diffuse Large B-cell Lymphoma and we highlight that mCNA results have a strong correlation with comparative genomic hybridization. Conclusion We provide mCNA, a new approach for CNV detection, freely available at https://gitlab.com/pierrejulien.viailly/mcna/ under MIT license. mCNA can significantly improve detection accuracy of CNV changes by using UMI.https://doi.org/10.1186/s12859-021-04060-4UMICNV callingNext generation sequencing |
| spellingShingle | Pierre-Julien Viailly Vincent Sater Mathieu Viennot Elodie Bohers Nicolas Vergne Caroline Berard Hélène Dauchel Thierry Lecroq Alison Celebi Philippe Ruminy Vinciane Marchand Marie-Delphine Lanic Sydney Dubois Dominique Penther Hervé Tilly Sylvain Mareschal Fabrice Jardin Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers BMC Bioinformatics UMI CNV calling Next generation sequencing |
| title | Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers |
| title_full | Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers |
| title_fullStr | Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers |
| title_full_unstemmed | Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers |
| title_short | Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers |
| title_sort | improving high resolution copy number variation analysis from next generation sequencing using unique molecular identifiers |
| topic | UMI CNV calling Next generation sequencing |
| url | https://doi.org/10.1186/s12859-021-04060-4 |
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