Polyfun annotations with Zoonomia genome conservation

Dataset from: "Leveraging Base Pair Mammalian Constraint to Understand Genetic Variation and Human Disease"

Abstract: 
Although thousands of genomic regions have been associated with heritable human diseases, attempts to elucidate biological mechanisms are impeded by a general inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function that is agnostic to cell type or disease mechanism. Here, single base phyloP scores from the whole genome alignment of 240 placental mammals identified 3.5% of bases in the human genome as significantly constrained and very likely functional. We compared these scores to large-scale genome annotation, genome-wide association studies (GWAS), copy number variation, clinical genetics findings, and cancer data sets. Evolutionary constrained positions are enriched for variants explaining common disease heritability more than any other functional annotation. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.

Dataset description: functional annotations of the human common genetic variants including conservation metrics across 240 mammals and subset of primates. These annotations are to be used in conjunction with the polyfun method.

数据集来源：

摘要：尽管成千上万的基因组区域与遗传性人类疾病相关联，但揭示生物机制的尝试受到一个普遍的障碍，即无法辨别哪些基因组位置具有功能性重要性。进化约束是一种强大的功能预测工具，它对细胞类型或疾病机制具有无偏见性。在本研究中，通过对240种有袋类哺乳动物的整个基因组比对，单碱基phyloP得分识别出人类基因组中3.5%的碱基受到显著约束，并且极有可能具有功能。我们将这些得分与大规模基因组注释、全基因组关联研究（GWAS）、拷贝数变异、临床遗传学发现和癌症数据集进行了比较。进化约束位置富含解释常见疾病遗传性的变异，其比例高于其他任何功能性注释。我们的研究结果不仅提高了变异注释的准确性，而且还突显了人类基因组调控景观仍需进一步探索并与疾病相关联。

数据集描述：包含人类常见遗传变异的功能性注释，以及240种哺乳动物和灵长类动物子集的保守性度量。这些注释应与polyfun方法结合使用。