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的不良来源，现在被认为是历史DNA （hDNA）的潜在巨大生物资源，它提供了过去200年来无与伦比的生物多样性记录。特别是，高通量测序平台（使用短DNA片段）的出现现在提供了一种更有效的DNA基因组采样方法。然而，DNA的潜力几乎尚未被探索，目前的DNA提取程序通常依赖于在少数个体上测试的方法，并针对特定项目进行了优化。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，或者导致高测序错误、数据缺失和/或污染。该项目将利用美国自然历史博物馆（AMNH）的时间序列标本，通过对现有和新型DNA提取方法的严格对比实验，开发高效和开源的协议，从典型的传统博物馆标本中获得可用的基因组尺度分子数据。更广泛的社会影响包括保护（利用博物馆标本记录人口和新出现的疾病的历史趋势）、法医学（为准确识别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DNA的最佳组织来源和提取方法，开发福尔马林固定DNA反交联的改进方法，并深入了解DNA在暴露于福尔马林、酒精、组织缓冲液和档案储存时间下是如何降解的。该项目还将开发dna生物信息学处理的新方法，以更好地检测污染，评估dna对系统发育推断的影响，并提高dna在比较生物学各个方面的效用。这项研究产生的可靠的生物信息学处理管道的应用将使遗传研究资源的可用性至少增加100倍（例如，在AMNH，现有的DNA组织样本有12万个，而生物博物馆的代金券有2000万个）。历史博物馆标本DNA的可用性也将使已灭绝物种和种群的遗传学和表观遗传学得以研究，并为确定遗传多样性在人类世期间如何变化提供令人兴奋的新机会。该项目的结果将在https://www.amnh.org/research.This上公布，该奖项反映了美国国家科学基金会的法定使命，并通过基金会的智力价值和更广泛的影响审查标准进行评估，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.