This is Figure 1 for the feature, “Blazing a Path to More Effective Infectious Disease Response.”

1605 PacBio-Korlach-Olsen_Figure 1_Ra

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A SMRT genome assembly corrected reference errors, resolving the genetic basis of virulence in Mycobacterium tuberculosis H37Ra.2 Here, a visualization of the reduced set of H37Ra-specific variants and their effect on phenotype. The new assembly contradicts many variants previously thought to be H37Ra-specific, reducing the number of genes that may contribute to H37Ra’s virulence attenuation. Several of these genes have been reassigned function since the first published assembly of the H37Ra genome. Top (a): the set of genes identified to carry H37Ra-specific polymorphisms in the original H37Ra reference genome, and their contribution to phenotype as understood at that time; 56 genes are affected, the majority of which were PE_PPE genes or were of unknown function. Bottom (b): the set of genes with H37Ra-specific variants confirmed by the new H37Ra assembly is reduced markedly, particularly in PE_PPE genes, highlighting the strength of single-molecule sequencing in resolving GC-rich and repetitive stretches of DNA. Genes with functions not yet characterized were also reduced significantly.