Whole genome sequencing (WGS), whole exome sequencing (WES) and clinical exome sequencing (CES) in patient care

Abstract

Next generation sequencing (NGS, also called Massively Parallel Sequencing) can be performed using a number of different platforms. The general process is very similar across them all: (1) extracted DNA is sheared into fragments (which, in targeted methods can be captured using probes); (2) these fragments are isolated physically on slides (usually called flow cells) or in emulsions and individually amplified, resulting in a library; and (3) the multiple individually amplified fragments are then simultaneously sequenced. After sequencing each fragment individually, the fragments must be re-assembled and the positions called using a series of bioinformatics algorithms. Excellent reviews are available that discuss the technical differences in detail. Recently, the value of NGS for diagnostics in patient care has been widely recognized and its applications include mutation detection in human genetics, molecular pathology and infectious agents as well as HLA typing, RNA sequencing and the detection of cell-free DNA. This paper focuses on applications of three different scales of NGS in human genetics diagnostics and evaluates its status based on our current understanding.