Insertion and deletion (indel) is one of the major variation types in human genomes. Accurate annotation of indels is of paramount importance in genetic variation analysis and investigation of their roles in human diseases. Previous studies revealed a high number of false positives from existing indel calling methods, which limits downstream analyses of the effects of indels on both healthy and disease genomes. In this study, we evaluated seven commonly used general indel calling programs for germline indels and four somatic indel calling programs through comparative analysis to investigate their common features and differences and to explore ways to improve indel annotation accuracy. In our comparative analysis, we adopted a more stringent evaluation approach by considering both the indel positions and the indel types (insertion or deletion sequences) between the samples and the reference set. In addition, we applied an efficient way to use a benchmark for improved performance comparisons for the general indel calling programs We found that germline indels in healthy genomes derived by combining several indel calling tools could help remove a large number of false positive indels from individual programs without compromising the number of true positives. The performance comparisons of somatic indel calling programs are more complicated due to the lack of a reliable and comprehensive benchmark. Nevertheless our results revealed large variations among the programs and among cancer types. While more accurate indel calling programs are needed, we found that the performance for germline indel annotations can be improved by combining the results from several programs. In addition, well-designed benchmarks for both germline and somatic indels are key in program development and evaluations.

中文翻译：

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利用下一代测序数据比较评估健康和癌症基因组中indel注释

插入和缺失（indel）是人类基因组中的主要变异类型之一。在基因变异分析和调查其在人类疾病中的作用时，对indel进行准确注释至关重要。先前的研究揭示了现有indel调用方法产生的大量误报，这限制了下游对indel对健康和疾病基因组影响的分析。在这项研究中，我们通过比较分析评估了七个针对种系插入缺失的通用插入缺失调用程序和四个躯体插入缺失调用程序，以研究它们的共同特征和差异，并探索提高插入缺失注释准确性的方法。在我们的比较分析中 我们通过考虑样本和参考集之间的插入缺失位置和插入缺失类型（插入或缺失序列），采用了更为严格的评估方法。此外，我们采用了一种有效的方法来使用基准，以改进常规indel调用程序的性能比较。我们发现，通过组合多个indel调用工具得出的健康基因组中的种系indel可以帮助从单个程序中删除大量假阳性indel。而不会损害真实肯定的数量。由于缺少可靠和全面的基准，因此体细胞indel调用程序的性能比较更加复杂。然而，我们的结果显示了程序之间和癌症类型之间的巨大差异。尽管需要更准确的indel调用程序，我们发现通过组合多个程序的结果可以提高种系插入/缺失注释的性能。此外，为种系和体细胞插入缺失设计良好的基准是程序开发和评估的关键。