Targeted analysis of metagenomes: divide and conquer

The rapidly developing field of targeted analysis of metagenomes focuses on retrieving information about specific genes and/or genome(s) from environmental DNA. The traditional shotgun sequencing methods overemphasise dominant microorganisms and often fail to confidently assign the entirety of the analysed genetic material to specific species, genomovars, or strains. The ultimate goal of the targeted methods is to overcome this limitation of throughput and precision of current shotgun metagenomics when analysing complex microbial communities in the quest of refined information. Here, we discuss recent technological advances that are designed to focus the analytical power of diagnostic tools like sequencing, towards phylogenetically or functionally distinct and rare microbial groups and enhance e.g. the confidence in the assignment of genetic elements to their respective owning organisms. We specifically showcase the capabilities of these technological advances for targeted analysis of metagenomes, identify suitable related applications, discuss methodological limitations, and propose solutions for addressing these limitations. This review aspires to inspire highly relevant experimental designs in the future that will unlock unknown and important aspects of microbial ecology, and the yet-uncultivated microbial majority.