PT - JOURNAL ARTICLE AU - Ohad Manor AU - Elhanan Borenstein TI - MUSiCC: A marker genes based framework for metagenomic normalization and accurate profiling of gene abundances in the microbiome AID - 10.1101/009407 DP - 2014 Jan 01 TA - bioRxiv PG - 009407 4099 - http://biorxiv.org/content/early/2014/11/14/009407.short 4100 - http://biorxiv.org/content/early/2014/11/14/009407.full AB - Functional metagenomic analyses commonly involve a normalization step, where measured levels of genes or pathways are converted into relative abundances. Here, we demonstrate that this normalization scheme introduces marked biases both across and within human microbiome samples and systematically identify various sample-and gene-specific properties that contribute to these biases. We introduce an alternative normalization paradigm, MUSiCC, which combines universal single-copy genes with machine learning methods to correct these biases and to obtain a more accurate and biologically meaningful measure of gene abundances. Finally, we demonstrate that MUSiCC significantly improves downstream discovery of functional shifts in the microbiome.MUSiCC is available at http://elbo.gs.washington.edu/software.html.