From Short Reads to Long Reads: Sequencing Technologies in Genomics and Gene Discovery

Dear Colleagues,

Background and Rationale

Long-read sequencing technologies have rapidly transformed genomics by enabling the characterization of complex genomic regions, structural variants, repetitive sequences, transcript isoforms, epigenetic modifications, and complete microbial and eukaryotic genomes. Advances in platforms such as Oxford Nanopore and PacBio HiFi sequencing have substantially improved read accuracy, throughput, and accessibility, creating new opportunities for both basic and applied biological research. At the same time, the increasing volume and complexity of long-read data have created significant computational challenges. Conventional short-read bioinformatics approaches are often insufficient for long-read datasets, necessitating the development of specialized algorithms, workflows, and analytical frameworks for read processing, genome assembly, variant detection, transcriptome analysis, metagenomics, epigenomics, and data interpretation. This Special Issue aims to bring together the recent methodological developments, biological applications, and computational innovations in long-read sequencing. It will provide a platform for researchers working across genomics, bioinformatics, computational biology, and related disciplines to present advances that are shaping the next generation of sequencing-based research.

Scope of the Special Issue

The Special Issue will welcome original research articles, reviews, perspectives, methods papers, and application-focused studies addressing, but not limited to, the following areas:

• Advances in long-read sequencing technologies, including PacBio HiFi and Oxford Nanopore sequencing;
• Novel basecalling, read correction, polishing, and quality-control approaches;
• Long-read genome and transcriptome assembly;
• Telomere-to-telomere and gap-free genome reconstruction;
• Structural variant and complex variant detection;
• Haplotype-resolved and population-scale genomics;
• Long-read RNA sequencing and isoform discovery;
• Single-cell and spatial applications of long-read sequencing;
• Epigenomic and direct methylation detection using long reads;
• Metagenomics and microbial genome reconstruction;
• Long-read sequencing in cancer and clinical genomics;
• Pathogen surveillance and infectious disease genomics;
• De novo assembly of complex and repetitive genomes;
• Pangenomics and graph-based genome analysis;
• Development and benchmarking of long-read bioinformatics tools;
• Machine learning and artificial intelligence for long-read data analysis;
• Integration of long-read and short-read sequencing data;
• Workflow development, reproducibility, and scalable computational pipelines;
• Cloud, high-performance, and distributed computing for long-read datasets;
• Challenges in data storage, visualization, annotation, and interpretation;
• Emerging applications of long-read sequencing in agriculture, biodiversity, and evolutionary genomics;
• Clinical translation, diagnostic applications, and future perspectives.

Objectives

The primary objectives of this Special Issue are to:

• Highlight recent technological and computational advances in long-read sequencing.
• Showcase innovative bioinformatics methods and analytical workflows.
• Present important biological and clinical applications enabled by long-read technologies.
• Address the current computational and methodological challenges in the analysis of long-read data.
• Promote integration between sequencing technology developers, computational scientists, and experimental researchers.
• Identify emerging trends and future directions for long-read genomics and bioinformatics.

Target Audience

The Special Issue will be of interest to researchers and professionals in genomics, bioinformatics, computational biology, molecular biology, genetics, microbiology, transcriptomics, epigenomics, precision medicine, and related fields. It is expected to attract contributions from both methodological researchers developing computational tools and experimental scientists applying long-read sequencing to biological and biomedical questions.

Expected Contributions

We anticipate contributions covering a broad range of topics, including novel algorithms and software, benchmarking studies, sequencing and computational workflows, biological discoveries enabled by long-read sequencing, and comprehensive reviews of emerging technologies and analytical approaches.

Particular emphasis will be placed on studies that demonstrate how long-read sequencing can overcome the limitations associated with conventional sequencing approaches and on computational innovations that improve the accuracy, scalability, reproducibility, and biological interpretation of long-read data.

Dr. Gaurav Sablok
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• bioinformatics
• long reads
• genomics
• transcriptomics
• algorithms