A Hitchhiker’s Guide to Long-Read Genomic Analysis

Authors

Medhat Mahmoud
Daniel P Agustinho
Fritz J Sedlazeck

Language

English

Publication Date

4-14-2025

Journal

Genome Research

DOI

10.1101/gr.279975.124

PMID

40228901

PMCID

PMC12047252

PubMedCentral® Posted Date

4-1-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Over the past decade, long-read sequencing has evolved into a pivotal technology for uncovering the hidden and complex regions of the genome. Significant cost efficiency, scalability, and accuracy advancements have driven this evolution. Concurrently, novel analytical methods have emerged to harness the full potential of long reads. These advancements have enabled milestones such as the first fully completed human genome, enhanced identification and understanding of complex genomic variants, and deeper insights into the interplay between epigenetics and genomic variation. This mini-review provides a comprehensive overview of the latest developments in long-read DNA sequencing analysis, encompassing reference-based and de novo assembly approaches. We explore the entire workflow, from initial data processing to variant calling and annotation, focusing on how these methods improve our ability to interpret a wide array of genomic variants. Additionally, we discuss the current challenges, limitations, and future directions in the field, offering a detailed examination of the state-of-the-art bioinformatics methods for long-read sequencing.

Keywords

Humans, Genomics, Sequence Analysis, DNA, High-Throughput Nucleotide Sequencing, Genome, Human, Computational Biology, Molecular Sequence Annotation

Published Open-Access

yes

Recommended Citation

Medhat Mahmoud, Daniel P Agustinho, and Fritz J Sedlazeck, "A Hitchhiker’s Guide to Long-Read Genomic Analysis" (2025). Faculty and Staff Publications. 5117.
https://digitalcommons.library.tmc.edu/baylor_docs/5117