|The first two principal components of the PCA undertaken using (a) SARS coronavirus complete spike protein nucleotide sequences, and (b) nucleotides selected by the RFA. Viral groups, defined by host species and season, are represented by ellipses of different colours: Human patient samples from 2002/2003 collected in early, mid and late epidemic phase are HP03E (green), HP03M (purple) and HP03L (yellow); 2004 Human samples are labelled HP04 (black); palm civets samples collected in 2003 and 2004 are labelled PC03 (blue) and PC04 (red); bat samples are labelled BT (magenta).|
|Superimposed 2-dimensional antigenic maps generated from predicted antigenic distances (in colour) using a machine learning algorithm to establish an explicit genotype to phenotype map; and from HI titre data (in grey).|
|Individual based model simulations of a mass drug administration (MDA) in 800 villages with different malaria epidemiological initial conditions. Left - 1 MDA set; Right - 2 MDA sets.|
Senior Scientist and Fellow
Malaria transmission dynamics and optimizing intervention planning.
I have been developing a fully dynamic transmission model to simulate targeted malaria elimination strategies (METF) currently undergoing in SE Asia. The model is to be calibrated to the METF transmission settings and run in real time to explore options for study design. It will also be used as a bridge to scale up by projecting the impact of large scale strategy options for larger populations with an additional cost element.
Genotype to phenotype mapping
Moving away from genome scan methods used for human GWAS (ultimately inappropriate for the short highly polymorphic genomes of RNA viruses), I have done some work demonstrating the potential of multi-class machine learning algorithms in inferring the functional genetic changes associated with phenotypic change (e.g. a virus crossing the species barrier). These methods allow to uncover a set of features/insights that ultimately could be quite relevant in understanding viral transmission across host species:
- They show that even distantly related viruses within a viral family share highly conserved genetic signatures of host specificity;
- Reinforce how fitness landscapes of host adaptation are shaped by host phylogeny;
- Highlight the evolutionary trajectories of RNA viruses in rapid expansion and under great evolutionary pressure.
These methods can serve as rigorous tools of emergence potential assessment, specifically in scenarios where rapid host classification of newly emerging viruses can be more important than identifying putative functional sites.
Algorithm in the diagnosis of febrile illness using pathogen-specific rapid diagnostic tests.
Pokharel S. et al, (2019), Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
High turnover drives prolonged persistence of influenza in managed pig herds.
Pitzer VE. et al, (2016), J R Soc Interface, 13
Estimating the Severity and Subclinical Burden of Middle East Respiratory Syndrome Coronavirus Infection in the Kingdom of Saudi Arabia
Lessler J. et al, (2016), American Journal of Epidemiology, 183, 657 - 663
Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies.
Slater HC. et al, (2015), Nature, 528, S94 - 101
Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia.
Dorigatti I. et al, (2015), Vaccine, 33, 3746 - 3751