ed the lowest E-value in Megablast.

16S and ITS Databases
---------------------

The YAP workflow incorporates high quality databases to verify 16S and ITS origin of sequences, check for chimeras and assign taxonomies. For bacterial 16S, the SILVA database[@b54] and a training dataset from the RDP project[@b55] were used. For fungal ITS, a custom database was built as follows. First, a seed database of the entire fungal ribosomal region consisting of 236 diverse ribosomal sequences was compiled by running NT BLAST on an annotated ribosomal region of *Aspergillus fumigatus* Af293[@b56]. Next, 155,136 unique ITS sequences were retrieved from the NCBI public database, aligned to the seed database and oriented in the 5′ to 3′ direction. Clustering was performed in two iterations. The first, at 100% sequence identity, yielded 149,266 clusters and the second, at 97% sequence identity, yielded 39,548 species level clusters. Annotations were reassigned for 2,153 sequences based on clustering results. Finally, 10,226 sequences taxonomically identified as "uncultured" were queried against the NCBI taxonomy database to obtain the maximum possible taxonomic resolution.

Data processing
---------------

After confirming that each of the two independent experimental replicates showed similar trends, sequence count data and the cytokine expression data from these two independent replications were combined. The GAPDH normalized cytokine mRNA expression levels and genera level relative abundances of sequences were log transformed to bring the numerical attributes of the dataset into the same dynamic range.

Exploratory analyses
--------------------

The 99.6% bootstrap CI of the Welch\'s test statistic was computed to assess significant differences in microbial diversity and cytokine expression levels between each of the treatment (vancomycin, PSG) and the control groups. Differences were deemed significant when the 99.6% CI did not include zero. The CI was computed using 10,000 bootstrap resamples of the data, was free of d