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

到目前为止，对体细胞突变的研究主要集中在癌症或其他严重疾病上，很少有人关注。 这类重要变异的基本生物学。因此，体细胞变异目录 将由SMAT网络产生，满足了一个基本的需求。为了建立这个目录，新的方法和 由于目前的方法不能全面评估躯体结构，因此需要采用方法 变异(SV)或转座子激活的规模，或有足够的分辨率。我们将开发小说 基于长读排序的计算方法，并将使这些方法得到广泛应用 在整个SMAHT网络中。这些方法将利用新的算法和机器学习 方法是可扩展的，并以更低的成本提供更低的错误率。将会有一个特别的焦点 关于转座子在基因组中移动的鉴定。为此，我们将实施 更好地注释和表征作为证据的插入和易位 换位。此外，我们将从长时间读取的测序数据中识别甲基化信号。 甲基化变化与体细胞和马赛克突变的相关性将揭示这些基因组如何 突变塑造了关键区域的甲基化模式，并可能影响基因。为了培养 与其他小组合作，我们将与SMAT测序和分析密切合作 中锋。多项活动，如形成NIST和SMAT体细胞变异基准，如 以及一年一度的黑客马拉松，将吸引来自世界各地的调查人员。该组织的历史 成功的方法开发将确保SMATH网络将收到有用的和 全面的新工具，以扩展体细胞和花叶SVS和转座的知识。

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.