讲座题目：Bionano下代单分子水平基因图谱仪-从头组装真正精准的复杂大基因组

讲座时间：9月12日（周二）下午4:00

讲座地点：生物楼二楼报告厅

主讲人：BioNano Genomics Inc 创始人&首席科技官 曹涵博士

主讲人简介：

  曹涵博士在美国普林斯顿大学电子工程系纳米结构实验室工作时创建了生物纳米基因技术公司（Bionano Genomics，Inc， San Diego, CA），该公司以美国国防部高级研究计划局（DARPA）资助项目为基础。他是纳米流体通道阵列单分子水平的全基因组核心分析技术的关键共同发明人。他独特的交叉学科经验包括分子生物学、基因工程、基因芯片和基因组序列技术的开发、单分子分析，以及硅晶微纳米流体芯片的设计和制造。曹博士在过去十年中主持和参与了多项美国联邦和州政府资助的超过一千六百万美元的技术研发基金项目，多年来参与美国政府生物纳米及基因组学基金资助的评审。他在国际著名科学期刊上发表多篇论文，包括世界上第一次应用两个长距单分子技术平台组装参照级别高精度人类基因组及目前最精度人类基因组， 并拥有多项专利。他负责Bionano Genomics公司在生物纳米及基因组学方向未来应用和技术开发, 公司在全世界首创并商业化了动态长距单分子基因组分析平台 (Irys and Saphyr系列), 改变了基因组研究现状，使高效低成本组装多个复杂参照级别高精度基因组成为现实，并与多家医疗诊断公司有战略合作。曹涵博士毕业于中国科技大学生物系，获得美国特拉华州大学分子生物学博士学位, 曾在北京大学国家植物和蛋白工程重点实验室，杜邦全球植物基因组研究中心，宾夕法尼亚大学医学中心担任研发工作。               

讲座摘要：

Building High-quality, de novo Complex Genome Assemblies with Bionano’s Next-Generation Mapping

         Han Cao, Bionano Genomics, San Diego, California, United States of America

Abstract

Combining next-generation sequencing (NGS) data and next-generation mapping (NGM) data from Bionano Genomics provides a solution that is being adopted to produce affordable, high-quality and chromosome-scale de novo genome assemblies. 

We describe a novel workflow that utilizes two nicking endonucleases to increase the information specificity and improve contiguity through tiling of sequence contigs and genome maps.  We generated two sets of genome maps, each with a different nicking endonuclease and developed novel algorithms that used the NGS sequences as a bridge to merge single-enzyme genome maps into combined maps that contain the sequence motif patterns from both nicking enzymes.  This improves the detection of assembly errors, the contiguity of the scaffolds and the incorporation of short NGS sequences in the final scaffold. 

For the human genome, we started with NGS assemblies with N50 ranging from 0.18 – 0.9 Mbp and produced hybrid assemblies with N50 from 18 to 38 Mbp and incorporated 80-90% of total sequences with over 99% accuracy.  Compared to previously published single-enzyme hybrid scaffolds, the two-enzyme approach improved the scaffold contiguity by 300% and anchored up to 30% more sequence contigs while correcting 50% more assembly errors.  We furthermore demonstrated that the pipeline is compatible with data from different sequencing technologies and performs well across human, animal and plant genomes. This NGM-based approach makes assembling large complex genomes cost-effective. With Bionano’s new Saphyr platform, the two-enzyme data for a human genome can be collected in 24 hours with 1 chip and relatively low reagent costs.

Bionano System is compatible with many sample types. Here, we demonstrate its versatility, as it was used to map hundreds of genomes from a variety of sample sources, including blood, plant tissue, and whole animals. We present a catalog of genomes assembled using Bionano systems to date, showing how NGM technology was used to scaffold and finish reference genomes from birds, mammals, invertebrates, and plants.