Metagenomic shotgun sequencing can be used for direct taxonomic profiling of complex microbial communities, thus enabling a faster and more accurate alternative in comparison to culture-based identifications. Shotgun sequencing data analysis usually involves alignment to one large reference, which is easily accomplished with a standard PC. Microbial shotgun sequencing data analysis is a more complex problem, since each read has to be compared to many, and sometimes millions of relatively small reference sequences which is a bottleneck for most existing analysis techniques. Current computational approaches fall into two broad categories. The first group�Cmarker-based methods�Cseeks to bypass the bottleneck via search space reduction, using dedicated, small Phosphatase Inhibitor Cocktail (EDTA-Free) datasets. A typical example is 16S RNA analysis wherein a dataset of short sequence items is searched with sensitive alignment techniques, such as BLAST. While this is the traditional standard for taxonomic identification, it has well known limitations, EG00229 including the need for PCR amplification that introduces extra overhead as well as experimental bias. Alternatively, wordbased techniques combined with artificial intelligence can be used to construct a database of clade-specific recognizers that make it possible to use rapid string matching techniques for species identification. Finally, the MetaPhlAn program uses a small clade-specific sequence marker database built from the genome sequences of the known taxa that can be searched with generalpurpose aligners. This search is extremely fast and accurate for determining taxa and their approximate proportions within large microbial communities. A potential common drawback of markerbased approaches is the frequent lack of lower taxon identification, as the markers are often identical for many strains. In the second group of metagenome sequencing approaches, whole genome shotgun sequencing reads are directly aligned against a comprehensive sequence database. In this group of approaches database search is a critical step since aligning a large set of reads against a comprehensive database using high quality aligners such as BLAST is either too time consuming or requires computational resources that that are not readily available for all research groups.