A version of the human genome (hg19) originally masked for ribosomal, plant, animal, fungal and low-entropy sequences by Brian Bushnell (Bushnell Masked Human Genome) additionally masked for all possible viral sequences. The following commands were used to generate the additional virus sequence masked reference database: 1) Download all RefSeq and Neighbor nucleotide records: https://www.ncbi.nlm.nih.gov/nuccore/?term=Viruses[Organism]%20NOT%20cellular%20organisms[ORGN]%20NOT%20wgs[PROP]%20NOT%20gbdiv%20syn[prop]%20AND%20(srcdb_refseq[PROP]%20OR%20nuccore%20genome%20samespecies[Filter]) 2) Shred the downloaded viral genomes using shred.sh from the bbtools package shred.sh in=refseq_virus_reformated.fasta out=virus_shred.fasta.gz length=85 minlength=75 overlap=30 3) Map shredded virus sequence to the hg19-masked human genome using bbmap.sh from the bbtools package bbmap.sh ref=hg19_main_mask_ribo_animal_allplant_allfungus.fa.gz in=virus_shred.fasta.gz outm=map_human_all_viruses.sam minid=0.90 4) Mask virus sequenced mapped regions from the hg19-masked human genome using bbmask.sh from the bbtools package bbmask.sh in=hg19_main_mask_ribo_animal_allplant_allfungus.fa.gz out=human_virus_masked.fasta.gz sam=map_human_all_viruses .sam 5) Remove all N's to further reduce file size using seqkit seqkit -is replace -p "n" -r "" human_virus_masked.fasta.gz > human_virus_masked.fasta_Ns_removed.gz Additional References: http://seqanswers.com/forums/showthread.php?t=42552 for additional information on the original masking of hg19 bbtools seqkit NCBI Virus Genome RefSeq