Alternative splicing: Human disease and quantitative analysis from high-throughput sequencing.

Area of Science:

• Molecular Biology
• Genomics
• Bioinformatics

Background:

• Alternative splicing is a key mechanism generating protein diversity in eukaryotes, with up to 95% of human multi-exon genes undergoing this process.
• Dysregulation of alternative splicing is implicated in approximately 15% of human hereditary diseases and cancers.
• The intricate regulation of alternative splicing is crucial for fundamental biological processes like cell development and differentiation.

Purpose of the Study:

• To review the mechanisms and regulatory networks governing alternative splicing.
• To explore the association between alternative splicing events and human diseases, including cancer.
• To provide an overview of computational tools for quantifying alternative splicing and isoforms from RNA-sequencing (RNA-seq) data.

Main Methods:

• Literature review of alternative splicing mechanisms, regulation, and disease associations.
• Survey of existing computational approaches and software for alternative splicing analysis from RNA-seq data.
• Synthesis of current knowledge on the challenges and advancements in isoform quantification.

Main Results:

• Alternative splicing significantly expands the proteome, contributing to cellular complexity and function.
• Aberrant alternative splicing patterns are recognized as significant contributors to various pathologies.
• Accurate isoform quantification from RNA-seq remains a complex computational challenge, necessitating advanced bioinformatics tools.

Conclusions:

• Understanding alternative splicing is critical for deciphering gene function and disease etiology.
• Computational tools are essential for accurate analysis of alternative splicing events and their clinical relevance.
• Further development in bioinformatics is needed to improve the accuracy of isoform quantification from high-throughput sequencing data.