lorikeet

Lorikeet analyzes whole-genome sequencing data to reconstruct the acquisition, timing, and spread of drug-resistance mutations in Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains.

Key Features:

• Whole Genome Sequencing Analysis: Performs comparative genomics and phylogenetic analysis of clinical M. tuberculosis isolates using whole-genome sequencing data.
• Drug Resistance Mutation Tracking: Determines the order and timing of acquisition of drug resistance mutations, including mutations conferring resistance to isoniazid, rifampicin, and streptomycin.
• Evolutionary Dynamics Assessment: Assesses relatedness among strains and estimates the number of independent evolutionary events leading to MDR and XDR phenotypes.
• Compensatory Mutation Identification: Identifies compensatory mutations that arise alongside primary resistance mutations to refine understanding of resistance evolution.
• Historical Contextualization: Estimates the timing of mutation acquisitions (for example, dating isoniazid and streptomycin resistance to 1957) and contextualizes outbreaks such as the Tugela Ferry XDR-TB outbreak in KwaZulu-Natal, South Africa.

Scientific Applications:

• Epidemiological Studies: Traces genetic evolution and transmission patterns of M. tuberculosis to inform analyses of outbreak dynamics and lineage spread.
• Public Health Interventions: Provides temporal and genetic evidence on the emergence of resistance to guide public health strategies and historical assessment of TB control vulnerabilities.
• Research on Drug Resistance Mechanisms: Supports investigation of the sequence of mutation acquisitions and compensatory mechanisms underlying persistence and fitness of drug-resistant M. tuberculosis.

Methodology:

Applies whole-genome sequencing, comparative genomics, and phylogenetic dating to clinical and historical M. tuberculosis isolates to construct timelines of mutation events.