Supporting data for "Chromosome-level de novo assembly of the pig-tailed macaque genome using linked-read sequencing and HiC proximity scaffolding"

Macaque species share over 93% genome homology with humans and develop many disease phenotypes similar to those of humans, making them valuable animal models for the study of human diseases (e.g.,HIV and neurodegenerative diseases). However, the quality of genome assembly and annotation for old world monkeys including macaque species lags behind the human genome effort. To close this gap and enhance functional genomics approaches, we employed a combination of de novo linked-read assembly and scaffolding using proximity ligation assay (HiC) to assemble the pig-tailed macaque (Macaca nemestrina) genome. This combinatorial method yielded large scaffolds at chromosome-level with a scaffold N50 of 127.5 Mb; the 23 largest scaffolds covered 90% of the entire genome. This assembly revealed large-scale rearrangements between pig-tailed macaque chromosomes 7, 12, and 13 and human chromosomes 2, 14, and 15. We subsequently annotated the genome using transcriptome and proteomics data from personalized induced pluripotent stem cells (iPSCs) derived from the same animal. Reconstruction of the evolutionary tree using whole genome annotation and orthologous comparisons among three macaque species, human and mouse genomes revealed extensive homology between human and pig-tailed macaques with regards to both pluripotent stem cell genes and innate immune gene pathways. Our results confirm that rhesus and cynomolgus macaques exhibit a closer evolutionary distance to each other than either species exhibits to humans or pig-tailed macaques. These findings demonstrate that pig-tailed macaques can serve as an excellent animal model for the study of many human diseases particularly with regards to pluripotency and innate immune pathways.

猕猴属物种与人类的基因组同源性超过93%，且可出现诸多与人类高度相似的疾病表型，故而成为研究人类疾病（如人类免疫缺陷病毒（HIV）感染与神经退行性疾病）的珍贵动物模型。然而，包括猕猴在内的旧世界猴的基因组组装与注释质量，仍远落后于人类基因组研究工作。为填补这一研究空白并优化功能基因组学研究手段，本研究结合从头连接读长组装（de novo linked-read assembly）技术，并辅以邻近连接测定（HiC）技术完成基因组支架构建，成功组装得到猪尾猕猴（Macaca nemestrina）的基因组。该联合组装方法获得了染色体级别的大片段基因组支架，其支架N50（scaffold N50）达到127.5 Mb；23个最大的基因组支架覆盖了全基因组90%的序列。本次组装结果揭示了猪尾猕猴7、12、13号染色体与人类2、14、15号染色体之间存在大规模染色体重排事件。随后，研究团队使用源自同一受试个体的个性化诱导多能干细胞（iPSCs）的转录组与蛋白质组数据，完成了该基因组的注释工作。基于全基因组注释结果，并对三种猕猴、人类与小鼠的基因组进行直系同源比较与进化树重构，结果显示人类与猪尾猕猴在多能干细胞相关基因以及先天免疫基因通路方面存在广泛的同源性。本研究证实，恒河猴与食蟹猕猴之间的进化亲缘关系，较二者分别与人类或猪尾猕猴的亲缘关系更为紧密。上述研究结果表明，猪尾猕猴可作为研究诸多人类疾病的优秀动物模型，尤其适用于多能性与先天免疫通路相关的人类疾病研究。