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Redundant reads were removed using the duplicate removal plugin in CLC.

Unincorporated radioactive nucleotides were removed using the QIAquick Nucleotide Removal kit (Qiagen).

Ribosomal RNAs were removed using the Ribo-Zero™ rRNA Removal Kit for Gram-Positive Bacteria (EPICENTRE Biotechnologies, Madison, WI).

Ocean tides (<100 m) were removed using the NAO.99Jb model (Matsumoto et al. 2000).

Generalized (containing R groups), inorganic compounds, and disconnected fragments were removed using the Pybel toolkit [39].

Multiple-copy genes in the T. brucei genome were removed using the list from [23].

Uncoupled dyes were removed using the Qiagen PCR Purification Kit according to the manufacturer's instructions.

Antibiotic resistance cassettes were removed using the temperature sensitive plasmid pCP20 carrying the FLP recombinase [66].

CD45+Ter119+ and CD31+ cells were removed using the EasySep biotin selection kit (StemCell Technologies) to obtain Lin− cells.

Prior to alignment, contaminant sequence reads exactly matching the 33bp Illumina GA adaptor sequence were removed using the MAQ program.

Residual primers were removed using the EXOSAPit (Amersham, Otelfingen, Switzerland).