Short Oligonucleotide Analysis Package (SOAP) was used to handle the large amounts of short reads generated by parallel sequencing [24] . Briefly, after filtering out highly repetitive sequences and adaptor sequences, the overlapping datasets between FTLS and healthy subjects were analyzed by subtracting fragments that mapped to both host genomic-plus-transcript and bacteria databases. The non-redundant reads were mapped onto a virus database downloaded from NCBI (ftp://ftp.ncbi.nih.gov/ genbank/). The resulting alignments were filtered to identify unique sequences by examining alignment (identity $80%) and Evalue scores (e#10 22 ). Filtered unique alignments were examined in the taxonomy database (NCBI) using a custom software application written in Perl (BioPerl version 5.8.5). Unmapped reads were examined in GenBank nucleic acid and protein databases using BLASTn and BLASTx, respectively [25] [26] [27] . Unique alignments were examined in the taxonomy database (NCBI). Sequences without hits were placed in the ''unassigned'' category. Sequences were phylotyped as human, bacterial, phage, viral, or other based on the identity of the best BLAST hit. Considering misannotation and low-complexity for Illumina short reads, sequences assigned to the same virus family were further assembled into contigs with Velvet 1.1.04 (K-mer length = 21; coverage cutoff: default 0; Insert length: PE only; minor contig length: 42) for direct comparison with GenBank nucleic acid databases using BLASTn [28] . Contigs were also blasted with GenBank protein databases using BLASTx [28] . An E-value cutoff of 1610 25 was applied to both BLASTn and BLASTx analyses. Sequences phylotyped as viral were placed in the ''viral'' category.