Identification of somatic/ mosaic SV and transposon activity and their crosstalk to DNA epigenetic Modifications

体细胞/嵌合 SV 和转座子活性的鉴定及其与 DNA 表观遗传修饰的串扰

• 批准号: 10662143
• 负责人: Fritz J Sedlazeck
• 金额: $ 29.48万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662143
• 关键词: Address; Algorithms; Attention; Awareness; Belief; Benchmarking; Biology; Blood; Brain; Catalogs; Collaborations; Communities; Complex; Computer software; Computing Methodologies; DNA; DNA Sequence; DNA Sequence Alteration; DNA Transposable Elements; Data; Detection; Disease; Elements; Ensure; Epigenetic Process; Ethnic Origin; Evaluation; Event; Feedback; Fostering; Frequencies; Gene Expression; Genes; Genome; Genomic Segment; Human; Human Genome; Individual; Knowledge; Laboratories; Liver; Location; Machine Learning; Malignant Neoplasms; Measures; Methodology; Methods; Methylation; Modification; Mosaicism; Movement; Mutation; Phase; Population; Production; Recording of previous events; Research Personnel; Resolution; Shapes; Short Tandem Repeat; Signal Transduction; Single Nucleotide Polymorphism; Somatic Mutation; Statistical Models; Tandem Repeat Sequences; Technology; Tissues; Variant; Work; analytical method; cost; genetic variant; hackathon; human reference genome; improved; insight; method development; methylation pattern; mosaic; mosaic variant; novel; tool; variant detection

Studies of somatic mutation have so far focused on cancer or other severe diseases, with little attention to the basic biology of this important class of variation. As a consequence, the somatic variation catalog to be produced by the SMaHT network fills an essential need. To build this catalog, novel methods and approaches are required since current methods cannot comprehensively assess somatic structural variation (SV) nor transposon activation at scale, or with adequate resolution. We will develop novel computational methods based on long-read sequencing and will make the methods broadly available across the SMaHT network. The approaches will leverage new algorithmic and machine learning approaches, be scalable and provide a reduced error rate, at lower cost. There will be a special focus on the identification of the movement of transposons across the genome. For this we will implement better annotation and characterization of insertions and translocations that are evidence for transposition. In addition, we will identify methylation signals from long-read sequencing data. Correlation of methylation changes and somatic & mosaic mutations will reveal how these genomic alterations shape the methylation patterns in critical regions and likely impact genes. To foster the collaboration with other groups we will closely work together with SMaHT sequencing and analysis centers. Multiple activities such as the formation of a NIST & SMaHT somatic variation benchmarks, as well as annual Hackathons, will engage investigators from around the world. The group’s history of successful methods development will ensure that the SMaHT network will receive useful and comprehensive new tools to extend the knowledge of somatic and mosaic SVs and transposition.

到目前 对于这种重要的变异类别的基本生物学。结果，躯体变化目录 由SMAHT网络生产的是满足了必要的需求。构建此目录，新颖的方法和 需要方法，因为当前方法无法全面评估躯体结构 变异（SV）或跨盆地激活，或以足够的分辨率。我们将发展小说 基于长阅读测序的计算方法，将使这些方法广泛可用 跨越SMAHT网络。这些方法将利用新的算法和机器学习 方法，可扩展并以较低的成本提供降低的错误率。将有一个特别的重点 关于转座跨基因组运动的鉴定。为此，我们将实施 更好地注释和表征插入和易位的证据 换位。此外，我们将从长阅读测序数据中确定甲基化信号。 甲基化变化与体细胞和镶嵌突变的相关性将揭示这些基因组如何 改变塑造了关键区域中的甲基化模式，并可能影响基因。促进 与其他小组的合作我们将与SMAHT测序和分析密切合作 中心。多种活动，例如形成NIST和SMAHT躯体变异基准，如 以及一年一度的黑客马拉松，将与来自世界各地的调查人员互动。小组的历史 成功的方法开发将确保SMAHT网络将获得有用和 全面的新工具，以扩展有关体细胞和镶嵌SVS和换位的知识。