Abstract LB010: Identification of malignant lung indeterminate pulmonary nodules with Plasma WGS using exon read depth of short DNA fragments

Abstract

Abstract Background: Plasma WGS for non-invasive cancer detection has been an active area of research, where fragmentomics studies have been gaining attention for its promising results. Previous studies showed that the quantity of short and long fragments could be used for the prognosis of malignant tumor. In this study, the efficacy of short fragment read depth on the reference genome for malignant nodule detection was evaluated. Methods: Plasma samples from 40 patients with Indeterminate Pulmonary Nodules (IPN) (20 with Benign nodule, 20 Malignant) were collected for WGS. Low quality samples were filtered, and 31 patients (15 Benign, 16 Cancer) remained. Short fragments in each sample were extracted (30-99 bp) and exon read depth for each sample was obtained through human reference genome alignment. A proprietary data analytic machine learning pipeline using XGBoost was trained and tested using 10 fold cross validation. Results: XGBoost model testing accuracy was 96.77% in differentiating Benign and Cancer samples using read depth information from only 3 exons. GPR35’s ENSE00003591008.1, ZNF594-DT’s ENSE00002678218.2 and IGHGP’s ENSE00001819760.2 were the 3 exons used in the model. Hierarchical clustering using top features with differential read depth (p<0.001) was able to perfectly cluster the samples into the Benign group and the Malignant group. Conclusion: Read depth information of exon by short fragments from WGS plasma was able to differentiate patients with Lung benign nodules from patients with malignant nodules. This analysis demonstrates promises of developing diagnosis tools using exon read depths from plasma samples. Citation Format: Shun H. Yip, Neeti Swarup, Jason C. Hyun, Jordan C. Cheng, Raghuraman Ramamurthy, Edmund Wong, Irene Choi, Akanksha Arora, Denise Aberle, David TW Wong, Cheuk Y. Tang. Identification of malignant lung indeterminate pulmonary nodules with Plasma WGS using exon read depth of short DNA fragments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB010.