Research Topic

Alternative Splicing in Health and Disease

About this Research Topic

Alternative splicing is a fundamental molecular process in eukaryotes driving cellular differentiation, organ development and definition of tissue identity. In alternative splicing, non-coding intronic regions of precursor messenger RNAs are removed while protein-coding exons are inserted, deleted or combined into different mature RNA transcripts.

Alternative splicing plays an essential role in determining the functional complexity especially in the human genome. Protein isoforms generated through alternative splicing differ with respect to their molecular function, localization, enzymatic and interaction properties. Disruptions in the expression of these isoforms can cause multiple pathologies including cancer, neurological and immune disorders, as well as diabetes and heart diseases. Despite its significance, alternative splicing remains largely understudied with many biological questions unanswered; these include the extent and identity of isoforms expressed in various cell types, the effect of individual isoforms on the development of different diseases, and the delineation of cellular networks that determine splicing outcomes.

Most of our current knowledge on alternative splicing stems from recent high-throughput sequencing-based methods and their applications on transcriptomes. These technologies have enabled the collection of large catalogues of exon and transcript expression data in normal and disease tissues. In parallel, specialised bioinformatics tools and databases have been developed to detect, compare and visualize the data. Most recently, the development of new experimental and computational methods has shifted towards the detection of full-length transcripts with long-read sequencing technologies, the determination of alternative splicing events with single-cell sequencing, or the expression of protein isoforms with mass-spectrometry based proteomics. In parallel, analysis of alternative splicing in large patient cohorts, such as in pan-cancer studies, have highlighted the clinical relevance of alternative splicing patterns. This is illustrated with a proposed clinical usage of neoantigens that are generated through alternative splicing in cancer samples.

This Research Topic aims to highlight novel technological approaches to chart the landscape of alternative splicing in health and disease. The objective is to enhance our understanding of alternative splicing regulation, its phenotypic impact and potential clinical implications. We welcome conceptional papers, original research contributions, review papers as well as shorter papers on new software and database developments. Areas to be covered in this Research Topic include, but are not limited to:

• Alternative splicing in diseases
• Alternative splicing in cell identity
• Functional characterization of alternative splicing
• Regulation of alternative splicing
• Impact of alternative splicing on molecular interactions
• Therapeutic targets in alternative splicing
• Long-read sequencing technologies for detecting isoforms
• Isoform detection in single-cells
• Isoform detection on the proteome level


Keywords: Proteome complexity, Transcriptomics, Regulation, RNA-binding proteins, Networks


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Alternative splicing is a fundamental molecular process in eukaryotes driving cellular differentiation, organ development and definition of tissue identity. In alternative splicing, non-coding intronic regions of precursor messenger RNAs are removed while protein-coding exons are inserted, deleted or combined into different mature RNA transcripts.

Alternative splicing plays an essential role in determining the functional complexity especially in the human genome. Protein isoforms generated through alternative splicing differ with respect to their molecular function, localization, enzymatic and interaction properties. Disruptions in the expression of these isoforms can cause multiple pathologies including cancer, neurological and immune disorders, as well as diabetes and heart diseases. Despite its significance, alternative splicing remains largely understudied with many biological questions unanswered; these include the extent and identity of isoforms expressed in various cell types, the effect of individual isoforms on the development of different diseases, and the delineation of cellular networks that determine splicing outcomes.

Most of our current knowledge on alternative splicing stems from recent high-throughput sequencing-based methods and their applications on transcriptomes. These technologies have enabled the collection of large catalogues of exon and transcript expression data in normal and disease tissues. In parallel, specialised bioinformatics tools and databases have been developed to detect, compare and visualize the data. Most recently, the development of new experimental and computational methods has shifted towards the detection of full-length transcripts with long-read sequencing technologies, the determination of alternative splicing events with single-cell sequencing, or the expression of protein isoforms with mass-spectrometry based proteomics. In parallel, analysis of alternative splicing in large patient cohorts, such as in pan-cancer studies, have highlighted the clinical relevance of alternative splicing patterns. This is illustrated with a proposed clinical usage of neoantigens that are generated through alternative splicing in cancer samples.

This Research Topic aims to highlight novel technological approaches to chart the landscape of alternative splicing in health and disease. The objective is to enhance our understanding of alternative splicing regulation, its phenotypic impact and potential clinical implications. We welcome conceptional papers, original research contributions, review papers as well as shorter papers on new software and database developments. Areas to be covered in this Research Topic include, but are not limited to:

• Alternative splicing in diseases
• Alternative splicing in cell identity
• Functional characterization of alternative splicing
• Regulation of alternative splicing
• Impact of alternative splicing on molecular interactions
• Therapeutic targets in alternative splicing
• Long-read sequencing technologies for detecting isoforms
• Isoform detection in single-cells
• Isoform detection on the proteome level


Keywords: Proteome complexity, Transcriptomics, Regulation, RNA-binding proteins, Networks


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

15 January 2021 Abstract
14 May 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

15 January 2021 Abstract
14 May 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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