@article{Arres11022026,
author = {Arres, Judith and Elavalli, Santosh and Behl, Shalini and Matias Sanchez, Daniel and Al Ali, Ayesha and Saad, Abdelrahman Ahmed Yehia Abdelaziz and Attia, Azza and Minas, Cyla and Pariyachery, Sharika and Ahmed, Shariq and Aldhuhoori, Fatmah and Thulasidharan, Nitu and Katagi, Gurunath and Soliman, Omar and Purohit, Shilp and Kusuma, Vinay and Cardenas, Raony and Cardoso, Thyago and Paulin, Luis F. and Sanio, Philippe and Mafofo, Joseph and Wu, Haiguo and Zvereff, Val and El-Khani, Albarah and Al Marzooqi, Fahed and Magalhães, Tiago R. and Sedlazeck, Fritz J. and Quilez, Javier}, 
title = {Assessing the readiness of Oxford Nanopore sequencing for clinical genomics applications},
year = {2026}, 
doi = {10.1101/gr.280134.124}, 
abstract ={Long-read sequencing (LRS) technologies, namely, Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio), have emerged as promising solutions to overcome the limitations of short-read sequencing (SRS). Nevertheless, the still higher sequencing error rates compared with SRS, need for customized pipelines, rapidly updating software, and incipient scalability continue to present challenges for adopting ONT in standard clinical practice. Here we assess the performance of ONT (R9 and R10 chemistries) in comparison to Illumina and MGI across 17 well-characterized reference samples with 11 clinical variants representing nine different genetic diseases. To enable this, we have implemented a production-ready pipeline including SNV, indel, STR, SV, and CNV detection, alongside reporting key summary metrics to ensure high-quality data at the production sequencing level. Our results show high accuracy of ONT across SNVs (F-score 0.978–0.983) and SVs (F-score = 0.75) but still weaknesses across indels (F-score 0.659–0.758). However, we highlight that ONT accurately detected all four pathogenic indels as well as the performance improvement in exons and with the newer R10 chemistry. We further demonstrated the importance of long reads to detect clinically impactful variants such as a FMR1 pathogenic expansion, often misclassified by SRS as being in the premutation range. Our multiplatform analysis and Sanger validation uncovered a 1 bp error in the Coriell annotation for a cystic fibrosis–causing indel in GM07829. This work underscores the growing readiness of ONT for clinical applications, highlighting both its advancements and its potential for broader adoption in clinical genomics and large-scale operations.}, 
URL = {http://genome.cshlp.org/content/early/2026/02/11/gr.280134.124.abstract}, 
eprint = {http://genome.cshlp.org/content/early/2026/02/11/gr.280134.124.full.pdf+html}, 
journal = {Genome Research} 
}