Leveraging Mammalian Cancers, Platinum-Quality Genome Assemblies, and Large-Scale Data to Identify Mechanisms of Rare Human Cancers

项目摘要 研究不同物种的癌症提供了一个独特的机会来询问各种因素， 支持癌症的发生和发展并促进新治疗靶点的建模 伴有合并症和转移的自发性肿瘤的情况。虽然有大量的报道 动物园动物肿瘤的频率和多样性，它还没有系统地与过多的 基因组资源。促进比较肿瘤学研究从人类加一的过渡 或其他两个物种，以泛哺乳动物分析，我们建议建立一个泛哺乳动物肿瘤纲要 和门户网站，以方便地传播我们的资源。我们将开发和应用机器学习工具来检测 人类和非人类哺乳动物肿瘤中癌症出现和癌症抗性的模式。我们 这种方法提供了利用大量未充分研究的哺乳动物肿瘤数据与人类肿瘤数据的机会。 数据，以确定进化和癌症抗性之间的相互联系。这将使我们能够创造新的人类 通过对哺乳动物高通量生物学数据的综合分析发现癌症 物种我们提供了一种强大的方法，将高质量的参考基因组和来自 数百种哺乳动物物种的机器学习，这有希望挖掘进化遗传 是癌症发生和发展的基石。我们将开发和应用模型， 识别有效模拟罕见人类癌症的哺乳动物肿瘤，与合作者合作获得肿瘤 从最强识别的哺乳动物模型中提取样本，然后对这些样本进行测序和分析， 它们作为人类癌症模型的有效性。

PROJECT SUMMARY Studying cancer across a diverse array of species provides a unique opportunity to interrogate factors underpinning cancer initiation and progression and facilitating the modeling of new therapeutic targets in the setting of spontaneous tumors complicated by comorbidities and metastases. While there is extensive reporting of the frequency and diversity of tumors in animals from zoos, it has not been systematically linked to the plethora of genomic resources available. To facilitate the transition of comparative oncology studies from human plus one or two other species, to pan-mammalian analyses, we propose building a pan-mammalian tumor compendium and portal to easily disseminate our resource. We will develop and apply machine learning tools to detect patterns of cancer emergence and cancer resistance in human and non-human mammalian tumors. Our approach provides opportunities to leverage the largely understudied mammalian tumor data jointly with human data to identify reciprocal links between evolution and cancer resistance. This will allow us to make new human cancer discoveries through integrative analysis of high-throughput biological data in the context of mammalian species. We offer a powerful approach combining high-quality reference genomes and genomic data from hundreds of mammalian species with machine learning, that has the promise to unearth the evolutionary genetic underpinnings that are cornerstones of cancer initiation and progression. We will develop and apply models to identify mammalian tumors that effectively mimic rare human cancers, work with collaborators to acquire tumor samples from strongest identified mammalian models, then sequence and analyze these samples to validate their effectiveness as models of human cancers.