TY  - JOUR
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
Y1  - 2026/02/11 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.280134.124 
UR  - http://genome.cshlp.org/content/early/2026/02/11/gr.280134.124.abstract 
N2  - 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. 
ER  -