Main menu

Haplotype-aware variant calling enables high accuracy in nanopore long-reads using deep neural networks


Long-read sequencing has the potential to transform variant detection by reaching currently difficult-to-map regions and routinely linking together adjacent variations to enable read based phasing. Third-generation nanopore sequence data has demonstrated a long read length, but current interpretation methods for its novel pore-based signal have unique error profiles, making accurate analysis challenging.

Here, we introduce a haplotype-aware variant calling pipeline PEPPER-Margin-DeepVariant that produces state-of-the-art variant calling results with nanopore data. We show that our nanopore-based method outperforms the short-read-based single nucleotide variant identification method at the whole genome-scale and produces high-quality single nucleotide variants in segmental duplications and low-mappability regions where short-read based genotyping fails.

We show that our pipeline can provide highly-contiguous phase blocks across the genome with nanopore reads, contiguously spanning between 85% to 92% of annotated genes across six samples. We also extend PEPPER-Margin-DeepVariant to PacBio HiFi data, providing an efficient solution with superior performance than the current WhatsHap-DeepVariant standard.

Finally, we demonstrate de novo assembly polishing methods that use nanopore and PacBio HiFi reads to produce diploid assemblies with high accuracy (Q35+ nanopore-polished and Q40+ PacBio-HiFi-polished).

Authors: Kishwar Shafin, Trevor Pesout, Pi-Chuan Chang, Maria Nattestad, Alexey Kolesnikov, Sidharth Goel, Gunjan Baid, Jordan M. Eizenga, Karen H. Miga, Paolo Carnevali, Miten Jain, Andrew Carroll, Benedict Paten

入门指南

购买 MinION 启动包 Nanopore 商城 测序服务提供商 全球代理商

纳米孔技术

订阅 Nanopore 更新 资源库及发表刊物 什么是 Nanopore 社区

关于 Oxford Nanopore

新闻 公司历程 可持续发展 领导团队 媒体资源和联系方式 投资者 合作者 在 Oxford Nanopore 工作 职位空缺 商业信息 BSI 27001 accreditationBSI 90001 accreditationBSI mark of trust
Chinese flag