An approach for developing a blood-based screening panel for lung cancer based on clonal hematopoietic mutations
Ramu Anandakrishnan, Ryan Shahidi, Andrew Dai, Veneeth Antony, Ian J. Zyvoloski
Abstract
Early detection can significantly reduce mortality due to lung cancer. Presented here is an approach for developing a blood-based screening panel based on clonal hematopoietic mutations.
Introduction
Cancer is a leading cause of death in the US, second only to heart disease, with lung cancer accounting for an estimated 21% of these deaths [1]. Early detection of lung cancer has been shown to reduce mortality by 20% [2].
Materials and methods
For data from the Sequence Read Archive (SRA) [30], fastq files from the repository were aligned to the GRCh38 reference genome using the Burroughs-Wheeler aligner (BWA) v0.7.15 [31].
Results
In this study we first identified a set of 98 potentially pathogenic (non-passenger) CH mutations in TII cells in lung cancer tissue samples, following the approach in Ref [40] and detailed below.
Discussion
Differences in cohort selection and sequencing protocols, between lung cancer and non-cancer samples, can result in different variant profiles between the two sample sets. As a result, the Training and Validation stages may show artificially high accuracy but fail to accurately predict the probability on other independent datasets where the protocols may differ.
Conclusions
Early detection can significantly reduce the mortality rate due to lung cancer, yet the uptake of the currently approved low-dose computed tomography scan for lung cancer is limited.
Citation: Anandakrishnan R, Shahidi R, Dai A, Antony V, Zyvoloski IJ (2024) An approach for developing a blood-based screening panel for lung cancer based on clonal hematopoietic mutations. PLoS ONE 19(8): e0307232. https://doi.org/10.1371/journal.pone.0307232
Editor: Francesco Bertolini, European Institute of Oncology, ITALY
Received: May 1, 2024; Accepted: July 1, 2024; Published: August 22, 2024
Copyright: © 2024 Anandakrishnan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The datasets used in the current study are available in the Genomic Data Commons Data Portal (https://portal.gdc.cancer.gov/) and the Sequencing Read Archive (https://www.ncbi.nlm.nih.gov/sra) repositories. The accession numbers or identifiers for the datasets are listed in SI Table S1. Source code is available at https://sourceforge.net/projects/lung-cancer-screening-panel/.
Funding: This work was funded by the VCOM 2023 REAP grant #1038624(RA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0307232#sec014
