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：《利用碱基对水平哺乳动物演化约束解析遗传变异与人类疾病》 摘要：尽管已有数千个基因组区域被证实与遗传性人类疾病相关，但由于普遍无法精准辨识哪些基因组位点具备功能重要性，解析其背后生物学机制的尝试始终受阻。演化约束（Evolutionary constraint）是一种无需依赖细胞类型或疾病机制的强大功能预测指标。本研究基于240种胎盘哺乳动物的全基因组比对（whole genome alignment）结果计算得到单碱基phyloP得分，鉴定出人类基因组中3.5%的碱基处于显著约束状态且极有可能具有功能。我们将此类得分与大规模基因组注释、全基因组关联研究（Genome-Wide Association Studies, GWAS）、拷贝数变异（copy number variation）、临床遗传学发现以及癌症数据集开展对比分析。结果显示，演化约束位点对于解释常见疾病遗传力的变异富集程度，优于其他所有功能注释方法。本研究成果不仅优化了变异注释流程，同时也凸显出人类基因组调控图谱仍有待进一步探索，并需进一步构建其与疾病的关联机制。 数据集说明：本数据集包含人类常见遗传变异的功能注释，涵盖跨240种哺乳动物及部分灵长类的保守性度量指标。此类注释需与polyfun方法结合使用。