A FLOT1 host regulatory allele is associated with a recently expanded Mtb clade in patients with tuberculosis
Luo, Y.; Huang, C.-C.; Liu, Q.; Howard, N.; Li, X.; Zhu, J.; Amariuta, T.; Asgari, S.; Ishigaki, K.; Calderon, R.; Moody, D. B.; Lecca, L.; Fortune, S. M.; Murray, M. B.; Raychaudhuri, S.
Show 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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania 97%
- Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage 94%
- IFN-γ-independent control of M. tuberculosis requires CD4 T cell-derived GM-CSF and activation of HIF-1α 93%
Similar papers in this journal
- Granuloma Dual RNA-Seq Reveals Composite Transcriptional Programs Driven by Neutrophils and Necrosis within Tuberculous Granulomas 95%
- DNA methylation enables recurrent endogenization of giant viruses in an animal relative 94%
- Selective clonal persistence of human retroviruses in vivo: radial chromatin organization, integration site and host transcription 94%
Similar papers in this journal
- Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung 95%
- A convolutional neural network highlights mutations relevant to antimicrobial resistance in Mycobacterium tuberculosis 95%
- Vibrio cholerae Type VI Secretion System Auxiliary Cluster 3 is a Pandemic-associated Mobile Genetic Element 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.