High-throughput Sequencing for Tuberculosis Diagnosis and Antimicrobial Resistance Detection: Progress, Challenges, and Future Perspectives

Tuberculosis (TB) continues to pose a significant threat to global public health, necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance (AMR) to facilitate timely clinical management. Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR, often resulting in delayed therapeutic interventions. High-throughput sequencing (HTS) technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy. In the context of TB, diverse sequencing strategies and platforms are being employed to fulfill specific research goals, ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates. This review systematically examines current progress in the application of HTS for rapid pathogen identification, comprehensive AMR profiling, epidemiological studies, advances in novel drugs, and vaccine development. Furthermore, we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.