A FLOT1 host regulatory allele is associated with a recently expanded Mtb clade in patients with tuberculosis

Code for the genome-to-genome study of tuberculosis

Abstract

The outcome of infectious diseases may depend on the interaction between human and pathogen genomic variations. We explore this relationship in tuberculosis (TB) by conducting a genome-to-genome (g2g) study of paired genomes from humans and the infectious agent Mycobacterium tuberculosis (Mtb) in 1,556 Peruvian TB patients. We identified a significant association between a human variant in the FLOT1 gene and a unique Mtb Lineage 2 (L2) subclade. The host allele affects FLOT1 expression in multiple tissue and cell types including lung, the primary site of TB disease. Phylogenetic analysis shows that the Mtb subclade has expanded rapidly in Peru since its emergence in the 1950s. Unbiased phenotypic profiling demonstrates that strains from the interacting Mtb subclade display different redox metabolism from other L2 strains. This study presents clear evidence that human and bacterial genetic variation interact together to produce different clinical outcomes.

Important Links

A preprint version of the manuscript can be found here https://www.medrxiv.org/content/10.1101/2022.02.07.22270622v1

Yang Luo, Chuan-Chin Huang, Qingyun Liu, Nicole Howard, Xinyi Li, Junhao Zhu, Tiffany Amariuta, Samira Asgari, Kazuyoshi Ishigaki, Roger Calderon, D. Branch Moody, Leonid Lecca, Sarah M Fortune, Megan B Murray, Soumya Raychaudhuri

medRxiv 2022.02.07.22270622; doi: https://doi.org/10.1101/2022.02.07.22270622

Organization

For all data used to preroduce figures in the paper, please see data/

For all scripts that reproduce figures in the paper, please see scripts/

For accessing the figures, please see figures/.