AUTHOR=Marco-Puche Guillermo , Lois Sergio , Benítez Javier , Trivino Juan Carlos TITLE=RNA-Seq Perspectives to Improve Clinical Diagnosis JOURNAL=Frontiers in Genetics VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01152 DOI=10.3389/fgene.2019.01152 ISSN=1664-8021 ABSTRACT=

In recent years, high-throughput next-generation sequencing technology has allowed a rapid increase in diagnostic capacity and precision through different bioinformatics processing algorithms, tools, and pipelines. The identification, annotation, and classification of sequence variants within different target regions are now considered a gold standard in clinical genetic diagnosis. However, this procedure lacks the ability to link regulatory events such as differential splicing to diseases. RNA-seq is necessary in clinical routine in order to interpret and detect among others splicing events and splicing variants, as it would increase the diagnostic rate by up to 10–35%. The transcriptome has a very dynamic nature, varying according to tissue type, cellular conditions, and environmental factors that may affect regulatory events such as splicing and the expression of genes or their isoforms. RNA-seq offers a robust technical analysis of this complexity, but it requires a profound knowledge of computational/statistical tools that may need to be adjusted depending on the disease under study. In this article we will cover RNA-seq analyses best practices applied to clinical routine, bioinformatics procedures, and present challenges of this approach.