Human genomic studies in infectious diseases seek to explain inter-individual differences in susceptibility and response to pathogens. In recent years, major advances in genetic knowledge, bioinformatics and technology have transformed the field and allowed, for the first time, comprehensive studies of the human genome without the limitations and bias inherent to candidate gene analyses. Genome-wide association studies have identified common genetic variants that associate with various infections. Now, ultra-high throughput sequencing makes it possible to scan the entire human genome for variants that are directly responsible for phenotypic variations, or to scan the whole transcriptome of specific cell populations in single assays.
Genomic technology, coupled with bioinformatics, make it possible to ask biological questions that were previously out of reach: the non-a priori screening of entire genomes represents a new frontier in the exploration of the complex interplay between human genetics and infections, and has the potential to improve our understanding of disease pathogenesis.
The work in the lab includes both classical genetics of infection susceptibility that measures clinical outcome, and a novel approach investigating the imprint of human polymorphisms on pathogen genetic diversity:
– In an effort to identify rare genetic variants conferring extreme susceptibility to specific infections, we use a combination of exome and RNA sequencing in patients with unusually severe clinical presentations upon infection with of HIV, hepatitis B virus and respiratory viruses, as well as in children with bacterial sepsis. Candidate genes and variants are then genetically validated and functionally characterized.
– Our group is leading a large international project that aims at understanding how human genetic variation impacts HIV control. In collaboration with >25 cohorts or centers, we have collected genome-wide genotyping data on ~11,000 HIV infected individuals with clinical follow-up, allowing an unprecedented description of the impact of common genetic variants on HIV disease.
– To improve understanding of human-virus interactions at the genomic level, we also developed an innovative strategy to simultaneously analyze host and pathogen genetic variation. We are currently applying it to HIV, hepatitis C virus, cytomegalovirus and Epstein Barr virus infections.
– We collaborate with colleagues from the EPFL I&C faculty to develop innovative solutions for genomic privacy, an essential trust-building component on to road toward genomic-based medicine.