RT Journal
A1 Arres, Judith
A1 Elavalli, Santosh
A1 Behl, Shalini
A1 Matias Sanchez, Daniel
A1 Al Ali, Ayesha
A1 Saad, Abdelrahman Ahmed Yehia Abdelaziz
A1 Attia, Azza
A1 Minas, Cyla
A1 Pariyachery, Sharika
A1 Ahmed, Shariq
A1 Aldhuhoori, Fatmah
A1 Thulasidharan, Nitu
A1 Katagi, Gurunath
A1 Soliman, Omar
A1 Purohit, Shilp
A1 Kusuma, Vinay
A1 Cardenas, Raony
A1 Cardoso, Thyago
A1 Paulin, Luis F.
A1 Sanio, Philippe
A1 Mafofo, Joseph
A1 Wu, Haiguo
A1 Zvereff, Val
A1 El-Khani, Albarah
A1 Al Marzooqi, Fahed
A1 Magalhães, Tiago R.
A1 Sedlazeck, Fritz J.
A1 Quilez, Javier
T1 Assessing the readiness of Oxford Nanopore sequencing for clinical genomics applications
JF Genome Research 
JO Genome Research 
YR 2026 
FD February 11 
DO 10.1101/gr.280134.124 
UL http://genome.cshlp.org/content/early/2026/02/11/gr.280134.124.abstract 
AB 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.