The Hormel Institute, University of Minnesota, 801 16th AVE NE, Austin, MN, 55912, USA.
Masonic Cancer Center, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA.
BMC Genomics. 2018 Apr 19;19(1):270. doi: 10.1186/s12864-018-4671-4.
Insertions and deletions (indels) are a major class of genomic variation associated with human disease. Indels are primarily detected from DNA sequencing (DNA-seq) data but their transcriptional consequences remain unexplored due to challenges in discriminating medium-sized and large indels from splicing events in RNA-seq data.
Here, we developed transIndel, a splice-aware algorithm that parses the chimeric alignments predicted by a short read aligner and reconstructs the mid-sized insertions and large deletions based on the linear alignments of split reads from DNA-seq or RNA-seq data. TransIndel exhibits competitive or superior performance over eight state-of-the-art indel detection tools on benchmarks using both synthetic and real DNA-seq data. Additionally, we applied transIndel to DNA-seq and RNA-seq datasets from 333 primary prostate cancer patients from The Cancer Genome Atlas (TCGA) and 59 metastatic prostate cancer patients from AACR-PCF Stand-Up- To-Cancer (SU2C) studies. TransIndel enhanced the taxonomy of DNA- and RNA-level alterations in prostate cancer by identifying recurrent FOXA1 indels as well as exitron splicing in genes implicated in disease progression.
Our study demonstrates that transIndel is a robust tool for elucidation of medium- and large-sized indels from DNA-seq and RNA-seq data. Including RNA-seq in indel discovery efforts leads to significant improvements in sensitivity for identification of med-sized and large indels missed by DNA-seq, and reveals non-canonical RNA-splicing events in genes associated with disease pathology.
插入和缺失（indels）是与人类疾病相关的主要基因组变异类型。indels 主要从 DNA 测序（DNA-seq）数据中检测到，但由于在 RNA-seq 数据中区分中等大小和大 indels 与剪接事件具有挑战性，其转录后果仍未得到探索。
在这里，我们开发了 transIndel，这是一种拼接感知算法，它解析短读比对器预测的嵌合比对，并根据来自 DNA-seq 或 RNA-seq 数据的拆分读的线性比对，重建中型插入和大型缺失。transIndel 在使用合成和真实 DNA-seq 数据的基准测试中，在八个最先进的 indel 检测工具上表现出有竞争力或优越的性能。此外，我们将 transIndel 应用于来自 TCGA 的 333 名原发性前列腺癌患者的 DNA-seq 和 RNA-seq 数据集，以及 AACR-PCF Stand-Up-To-Cancer（SU2C）研究中的 59 名转移性前列腺癌患者的 DNA-seq 和 RNA-seq 数据集。transIndel 通过鉴定 FOXA1 indels 以及与疾病进展相关的基因中外显子剪接，增强了前列腺癌中 DNA 和 RNA 水平改变的分类。
我们的研究表明，transIndel 是一种从 DNA-seq 和 RNA-seq 数据中阐明中等和大型 indels 的强大工具。在 indel 发现工作中包括 RNA-seq 可显著提高 DNA-seq 遗漏的中等和大型 indels 的检测灵敏度，并揭示与疾病病理学相关的基因中非典型的 RNA 剪接事件。
