Genomic Surveillance Project

Our genomic surveillance project integrates clinical research, genomics, clinical research, epidemiology, medical antropology, immunoinformatics, artificial intelligence, and molecular modeling–based state-of-the-art methods to understand sustained human-to-human transmission patterns, evolutionary dynamics, and identify drug targets for developing medical countermeasures (MCMs) against the contagious mpox virus (MPXV), thereby supporting evidence-based public health responses.

In collaboration with clinicians, virologists, and public health partners from various research institutes in the Democratic Republic of the Congo (DRC) and Uganda, our multidisciplinary research group has contributed to the characterization of emerging variants, recombinants, evolutionary dynamics, and transmission patterns of MPXV Clade Ib/sh2023, while developing tools and genomic resources for annotating genomes and screening therapeutic and vaccine candidates.

A major focus of our research has been the sequencing and annotation of the emerging Clade Ib/sh2023, which is responsible for multiple sustained human-to-human transmission outbreaks in the DRC and other African countries. Using an integrated whole-genome sequencing and evolutionary analysis approach on early clinical isolates of Clade Ib/sh2023 from Kamituga, we reported the first mutation map of Clade Ib/sh2023 and identified it as a distinct sub-lineage within Clade I. Based on proteome-wide mutation mapping, we identified seven proteins, namely, C9L (OPG047), I4L (OPG080), L6R (OPG105), A17L (OPG143), A25R (OPG151), A28L (OPG153), and B21R (OPG210), as mutation hotspots and found them to harbor consensus in-frame deletions, frameshift variants, synonymous variants, and amino acid substitutions. We also reported the complete deletion of the D14L (OPG032) gene and developed the first pangenome of MPXV clades. Through these studies, we highlighted genomic changes in Clade Ib MPXV and emphasized the importance of genomic surveillance for monitoring emerging MPXV variants.

Our group has also focused on the epidemiology and clinical presentation of individuals infected with MPXV during ongoing outbreaks. We have documented transmission patterns, clinical presentations, and outbreak dynamics of MPXV Clade Ib/sh2023 through cohort studies, with a primary focus on hospitalized patients, including children, adolescents, and adults.To understand patterns of co-infection, we investigated the trans-kingdom microbial spectrum of mpox-like lesion pustules from suspected patients using a metagenomics approach. This study helped uncover co-infection patterns and provided new perspectives on disease pathogenesis.

Recognizing the need for vaccine and therapeutic development against MPXV, our group is actively developing artificial intelligence (AI)-based tools and genomic resources to accelerate global research efforts aimed at identifying effective

treatments against emerging MPXV variants. We developed PoxiPred, an AI-based tool for high-throughput screening of protective antigens and epitopes across poxviruses in a proteome-wide manner. We have also established a comprehensive repository of predicted T-cell epitopes, named TCEPVDB. This database was developed with a goal to facilitate vaccine design and immunological research. These open-source resources help researchers identify promising vaccine targets and support next-generation vaccine development.

In addition, we are involved in the high-throughput screening of small chemical libraries against key MPXV drug targets using molecular modeling approaches. We continue to perform genome sequencing, epidemiological modeling, and the development of genomic resources and computational tools to monitor emerging variants and support the development of effective treatments against MPXV.