IIBR Informatics: Unlocking the incredible potential for museum specimens to yield DNA

传统的博物馆标本(如皮肤、骨骼、干燥和液体保存的标本)，曾经被认为是DNA的贫乏来源，现在正被认为是历史DNA(HDNA)的潜在巨大生物资源，它提供了跨越过去200年的无与伦比的生物多样性记录。特别是，高通量测序平台的出现(使用短DNA片段)现在提供了一种更有效的采样hDNA基因组的方法。然而，hDNA的潜力几乎还没有被发掘，目前的DNA提取程序往往依赖于在少数人身上进行测试并针对特定项目进行优化的方法。因此，大多数提取工作的结果仍然经常导致不可用的序列数据，或者以其他方式导致高测序错误、丢失数据和/或污染。该项目将开发高效和开源的协议，利用美国自然历史博物馆(AMNH)的时间序列收藏品，基于对现有和新的DNA提取方法的严格比较实验，从典型的传统博物馆标本中产生可用的基因组规模的分子数据。更广泛的社会影响包括保护(使用博物馆标本来记录人口和新出现的疾病的历史趋势)、法医学(为准确鉴定生物材料的物种提供改进的方法)和基因组学(记录过去200年的遗传变化)。项目成果将确定hDNA的最佳组织来源和提取方法，开发改进的福尔马林固定DNA反向交联方法，并提供更深入的了解DNA如何因暴露于福尔马林、酒精、组织缓冲区和档案存储时间而降解。该项目还将开发新的hDNA生物信息学处理方法，以更好地检测污染，评估hDNA在系统发育推断中的作用，并提高hDNA在比较生物学各个方面的应用。这项研究产生的可靠生物信息处理管道的应用将使遗传研究资源的可获得性扩大至少100倍(例如，在AMNH，目前的DNA组织样本为120,000个，而生物博物馆代金券为2,000万个)。从历史博物馆标本中获得DNA还将使人们能够研究灭绝物种和种群的遗传学和表观遗传学，并提供令人兴奋的新机会，以确定基因多样性在人类世期间发生了怎样的变化。该项目的结果将在https://www.amnh.org/research.This奖上提供，该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Traditional museum specimens (e.g., skins, skeletons, dry- and fluid-preserved specimens), once considered poor sources of DNA, are now becoming recognized as a potential vast biological resource for historical DNA (hDNA), that provide an unparalleled record of biodiversity spanning the last 200 years. In particular, the advent of high-throughput sequencing platforms (using short DNA fragments) now provides a more efficient means of sampling the hDNA genome. However, hDNA’s potential has hardly yet been explored, with current procedures for DNA extraction often relying on approaches tested on few individuals and optimized for specific projects. Consequently, outcomes of most extraction efforts still often lead to unusable sequence data, or otherwise, high sequencing errors, missing data, and/or contamination. This project will develop efficient and open-source protocols for yielding usable genome-scale molecular data from typical traditional museum specimens, based on rigorous comparative experiments of existing and novel DNA extraction methods, using time-series collections at the American Museum of Natural History (AMNH). Broader societal impacts include conservation (using museum specimens to document historical trends in populations and emerging diseases), forensics (providing improved methods for accurate species identification of biological material), and genomics (documenting genetic change over the past 200 years).Project outcomes will determine optimal tissue sources and extraction methods for hDNA, develop improved methods for reverse crosslinking of formalin-fixed DNA, and provide a deeper understanding of how DNA degrades due to exposure to formalin, alcohol, tissue buffers, and archival storage time. This project will also develop new approaches for bioinformatic processing of hDNA, to better detect contamination, evaluate the effects of hDNA on phylogenetic inference, and improve the utility of hDNA in all aspects of comparative biology. The application of reliable bioinformatic processing pipelines produced from this study will scale-up the availability of genetic research resources by at least 100-fold (e.g., at AMNH, 120,000 current DNA tissue samples compared to 20 million biological museum vouchers). The availability of DNA from historical museum specimens will also allow the genetics and epigenetics of extinct species and populations to be studied and provide exciting new opportunities to determine how genetic diversity has changed during the Anthropocene. Results of the project will be provided at https://www.amnh.org/research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.