Towards accurate indel calling for oncopanel sequencing through an international pipeline competition at precisionFDA

Binsheng Gong; Samir Lababidi; Rebecca Kusko; Khaled Bouri; Sarah Prezek; Vishal Thovarai; Anish Prasanna; Ezekiel J Maier; Mahdi Golkaram; Xingqiang Sun; Konstantinos Kyriakidis; João Paulo Kitajima; Sayed Mohammad Ebrahim Sahraeian; Yunfei Guo; Elaine Johanson; Wendell Jones; Weida Tong; Joshua Xu

doi:10.1038/s41598-024-58573-y

Towards accurate indel calling for oncopanel sequencing through an international pipeline competition at precisionFDA

Sci Rep. 2024 Apr 8;14(1):8165. doi: 10.1038/s41598-024-58573-y.

Authors

Binsheng Gong¹, Samir Lababidi², Rebecca Kusko³, Khaled Bouri⁴, Sarah Prezek⁵, Vishal Thovarai⁵, Anish Prasanna⁵, Ezekiel J Maier⁵, Mahdi Golkaram⁶, Xingqiang Sun⁷, Konstantinos Kyriakidis⁸, João Paulo Kitajima⁹, Sayed Mohammad Ebrahim Sahraeian¹⁰, Yunfei Guo¹⁰, Elaine Johanson², Wendell Jones¹¹, Weida Tong¹, Joshua Xu¹²

Affiliations

¹ Division of Bioinformatics and Biostatistics, Office of Research, National Center for Toxicological Research, Office of the Chief Scientist, Office of the Commissioner, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA.
² Health Informatics Staff, Office of Data, Analytics, and Research, Office of Digital Transformation, Office of the Commissioner, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
³ Cellino Biotech, 750 Main Street, Cambridge, MA, 02143, USA.
⁴ Office of Regulatory Science and Innovation, Office of the Chief Scientist, Office of the Commissioner, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
⁵ Booz Allen Hamilton, McLean, VA, 22102, USA.
⁶ Illumina, Inc., San Diego, CA, 92122, USA.
⁷ Genetalks, Changsha, Hunan, China.
⁸ UC Santa Cruz Genomics Institute, Santa Cruz, CA, 95060, USA.
⁹ Mendelics, Av. Braz Leme, 1631-Santana, São Paulo, SP, 02511-000, Brazil.
¹⁰ Roche Sequencing Solutions, Santa Clara, CA, 95050, USA.
¹¹ Q squared Solutions Genomics, 2400 Elis Road, Durham, NC, 27703, USA.
¹² Division of Bioinformatics and Biostatistics, Office of Research, National Center for Toxicological Research, Office of the Chief Scientist, Office of the Commissioner, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA. Joshua.Xu@fda.hhs.gov.

Abstract

Accurately calling indels with next-generation sequencing (NGS) data is critical for clinical application. The precisionFDA team collaborated with the U.S. Food and Drug Administration's (FDA's) National Center for Toxicological Research (NCTR) and successfully completed the NCTR Indel Calling from Oncopanel Sequencing Data Challenge, to evaluate the performance of indel calling pipelines. Top performers were selected based on precision, recall, and F1-score. The performance of many other pipelines was close to the top performers, which produced a top cluster of performers. The performance was significantly higher in high confidence regions and coding regions, and significantly lower in low complexity regions. Oncopanel capture and other issues may have occurred that affected the recall rate. Indels with higher variant allele frequency (VAF) may generally be called with higher confidence. Many of the indel calling pipelines had good performance. Some of them performed generally well across all three oncopanels, while others were better for a specific oncopanel. The performance of indel calling can further be improved by restricting the calls within high confidence intervals (HCIs) and coding regions, and by excluding low complexity regions (LCR) regions. Certain VAF cut-offs could be applied according to the applications.

Keywords: Indel calling pipeline; Next-generation sequencing; Personalized medicine; Precision medicine; precisionFDA challenge.

MeSH terms

High-Throughput Nucleotide Sequencing*
INDEL Mutation*
Polymorphism, Single Nucleotide