from Nature Methods
The past decade has seen a transformation, fueled by the availability of NGS platforms, in applications based on generating DNA and RNA sequence. There are more than 50 multiletter-acronym or ‘MLA-seq’ applications for interrogating a wide variety of genome characteristics. One of the first was RNA-seq, for transcript quantification and characterization. This quickly eclipsed microarrays for its superior dynamic range, sensitivity and ability to discover transcripts not included in the microarray probe set. RNA-seq has greatly expanded the view of the transcriptome, underpinning the importance of non–protein coding transcripts. Chromatin immunoprecipitation sequencing (ChIP-seq) allowed the genome-wide positioning of protein-DNA interactions, including transcription factor binding sites and histone modification patterns related to gene expression. Epigenetic DNA modifications such as methylation have been assayed using whole-genome sequencing of bisulfite-treated DNA (WGBS-seq). These and other methods have led to comprehensive catalogs of functional genomic elements, best exemplified by the 2012 release of 30 manuscripts describing more than 1,600 annotation data sets for the Encyclopedia of DNA Elements (ENCODE), a project started shortly after the completion of the human genome to provide functional insight into the landmark DNA sequence framework. More improvements are needed to these workflows to make these functional element assays as robust and efficient as the determination of single base substitutions.